Kidney/Renal Cancer

Condition: Metastatic Clear Cell Renal Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06783348

Sponsor: European Organisation for Research and Treatment of Cancer - EORTC

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum 100 Years
• Gender: All

Inclusion Criteria:

• PRE-SCREENING
• Histologically proven ccRCC. Sarcomatoid component is allowed.
• Adult patients ≥18 years old.
• Has progressed on or after ≥1-line prior systemic therapy approved in the metastatic setting. Prior treatment must include an anti-programmed death-1 (receptor) [PD-1]/programmed death-ligand 1 (PD-L1) therapy +/- ipilimumab and a VEGFR-TKI.
• Written pre-screening informed consent according to ICH/GCP and local regulations. SCREENING
• Patients with at least one PSMA-positive metastatic lesion, and no exclusionary PSMA-negative lesions, with positive lesions defined as those with a maximum standardized uptake value (SUVmax) greater than the mean standardized uptake value (SUVmean) of liver background.
• Measurable disease by RECIST 1.1 criteria.
• Patients with adequate blood tests (Absolute neutrophil count > 1.5 x 109/L, haemoglobin > 9.0 g/dL, platelet count > 100,000/µL, estimated glomerular filtration rate (GFR) ≥ 40 ml/min by CKD-EPI formula, total bilirubin ≤ 1.5 x ULN. Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN (≤ 5 x ULN in patients with liver metastases).
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Women of childbearing potential (WOCBP) must have a negative serum (or urine) pregnancy test within 72 hours prior to registration. A positive urine pregnancy test result must immediately be confirmed using a serum test. A pregnancy test is to be reported within 7 days prior to the first dose of the study treatment. Note: women of childbearing potential are defined as premenopausal females capable of becoming pregnant (i.e., females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrhoeic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antioestrogens, low body weight, ovarian suppression, or other reasons.
• Patients of childbearing / reproductive potential should use adequate birth control measures during the study treatment period and for at least 14 weeks after the last dose of treatment. A highly effective method of birth control is defined as a method which results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. Such methods include:
• Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
• Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Bilateral tubal occlusion
• Vasectomized partner
• Sexual abstinence (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient)
• Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 3 months after the last study treatment.
• Before patient's enrolment, written informed consent must be given according to ICH/GCP, and national/local regulations. This includes consent to comply to recommended radioprotection precautions during study.

Exclusion Criteria:

• Patient with RCC in a single kidney.
• Patients with PSMA-negative lesions (defined as PSMA uptake equal to or lower than that of liver parenchyma) in any lymph node with a short axis of at least 15 mm, in any metastatic solid-organ lesions with a short axis of at least 1.0 cm, or in any metastatic bone lesion with a soft-tissue component of at least 1.0 cm in the short axis. Patients with any PSMA-negative metastatic lesion meeting these criteria are ineligible.
• Other malignancy that is expected to interfere with the treatment or results of this study, such as prostate cancer.
• Patient with active uncontrolled or symptomatic central nervous system (CNS metastases). Note: patients treated previously with radiotherapy and/or surgery resulting in controlled/asymptomatic CNS disease are allowed.
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed and discussed with the patient before the enrolment in the in the trial.
• Known contraindication to imaging tracer or any product of contrast media.

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Condition: ccRCC, Complex Renal Cyst

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06949215

Sponsor: Peking Union Medical College Hospital

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Inclusion Criteria:

1. Age ≥ 18 y
2. Presence of complex renal cyst (Bosniak category II or higher)
3. Scheduled for surgical resection of renal mass (partial or total nephrectomy, open, laparoscopic, or robot-assisted technique)
4. Expected survival of at least 3 months
5. ECOG ≤ 2
6. Written informed consent provided for participation in the trial
7. In the opinion of investigator, willing and able to comply with required study procedures.

Exclusion Criteria:

1. On VEGF TKI treatment less than 1 week before 68Ga-NYM096 PET/CT. TKI is known to affect girentuximab binding in patients with ccRCC and is expected to have the same effect on 68Ga-NYM0
2. If patients were on VEGF TKI treatment, such as sunitinib, sorafenib, cabozantinib, pazopanib, or lenvatinib, a washout of one week before 68Ga-NYM096 PET/CT is required.
3. Intercurrent medical condition that renders the patient ineligible for surgery.
4. Pregnancy or breastfeeding.
5. Severe claustrophobia.

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Condition: Active Surveillance, Clear Cell Renal Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT07023432

Sponsor: M.D. Anderson Cancer Center

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Inclusion Criteria:

• 1. Metastatic clear cell renal cell carcinoma, with or without sarcomatoid features, clinically apparent less than 12 months. 2. Male/female participants must be at least 18 years of age on the day of signing informed consent. 3. IMDC risk score of 0 or 1. 4. No prior systemic treatment for ccRCC. Adjuvant immunotherapy or targeted treatments allowed if progressive disease is noted at least 12 months after last dose of immunotherapy. 5. Metastatic disease that is documented by imaging with CT or MRI and measurable by RECIST1.1. 6. Participants must have signed and dated an Institutional Review Board (IRB)/Institutional Ethics Committee (IEC) approved written informed consent form (ICF) in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal participant care. 7. Karnofsky performance status ≥ 70% and ECOG PS 0 or 1 8. Suitable for active surveillance in the medical judgment of the treating oncologist. 9. Participants must have adequate organ and marrow function as defined below: i. absolute neutrophil count ≥ 1.5 x 109/L ii. platelets ≥ 100 x 109/L iii. hemoglobin (Hgb) ≥ 9 g/dL iv. total bilirubin ≤ 1.5 x Institutional upper limit of normal (ULN) v. AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN vi. serum creatinine ≤ 1.5 × institutional ULN OR 24-hour clearance ≥ 40 mL/min *Aspartate aminotransferase (serum glutamic-oxaloacetic transaminase)-AST(SCOT)/ Alanine aminotransferase (serum glutamic-pyruvic transaminase)- ALT(SGPT) 10. A minimum of 28 days from any major surgery prior to registration. 11. Ability to swallow, retain, and absorb oral medication. 12. Baseline oxygen saturation >92% on room air. 13. Female Participants are eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
• Is not a woman of child-bearing potential (WOCBP) OR
• Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 30 days after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention.
• A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention.
• If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
• The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
• Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 14. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 7 days after the last dose of study intervention:
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR
• Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause as detailed below:
• Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
• Male participants must also agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person of any sex.
• Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 15. Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

Exclusion Criteria:

1. Known or suspected brain metastases or active leptomeningeal disease.
2. Requires any supplemental oxygen (either intermittent or chronic)
3. Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with protocol
4. Impairment of gastrointestinal function or disease that may significantly alter the absorption of belzutifan (e.g., uncontrolled nausea, vomiting, diarrhea, malabsorption syndromes, prior small bowel resection, or inflammatory bowel disease)
5. Prior cardiovascular event including myocardial infarction, rest claudication, stroke, unstable angina, central nervous system (CNS) hemorrhage, unstable ventricular arrythmias, or severe congestive heart failure (NYHA Class 3 or higher) within the past 6 months
6. Received colony-stimulating factors (eg, granulocyte colony stimulating factor, granulocytemacrophage colony stimulating factor or recombinant erythropoietin) ≤28 days prior to the first dose of study intervention.
7. Has moderate to severe hepatic impairment (Child-Pugh B or C).
8. Participants who have undergone major surgery ≤ 28 days prior to starting study drug, radiation ≤ 2 weeks prior to starting study drug, or who have not recovered from side effects of such therapy prior to registration.
9. Has received any type of small molecule kinase inhibitor (including investigational agents) ≤2 weeks before randomization; any prior HIF-2a antagonist exposure.
10. Has known hypersensitivity or allergy to the active pharmaceutical ingredient or any component of the study intervention (belzutifan) formulations.
11. Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate (eg, bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued for the duration of the study.
12. Active infection requiring systemic therapy within 14 days prior to treatment assignment.
13. Has active tuberculosis.
14. Active HBV (defined as HBsAg reactive and detectable HBV viral load) or active HCV (defined as HCV RNA [qualitative] is detected) infection.
15. Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
16. Has uncontrolled HIV infection (history of HIV with CD4 count >400 and undetectable HIV viral load while on anti-retroviral therapy allowed).
17. Pregnant women are excluded from this study. Women who are breastfeeding should discontinue prior to initiating treatment.

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Condition: Kidney Cancers

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT07590310

Sponsor: Peking University Cancer Hospital & Institute

Phase: Early Phase 1

Eligibility:

• Age: minimum 18 Years maximum 75 Years
• Gender: All

Inclusion Criteria:

• -Hematological, hepatic, and renal functions meeting the following criteria: Complete Blood Count: WBC ≥4.0×10⁹/L or Neutrophils ≥1.5×10⁹/L, PLT ≥100×10⁹/L, Hb ≥90 g/L; Coagulation: PT or APTT ≤1.5 × ULN (Upper Limit of Normal); Hepatic Function: T-Bil ≤1.5 × ULN; ALT/AST ≤2.5 × ULN (or ≤5 × ULN for subjects with liver metastases); ALP ≤2.5 × ULN (or ≤4.5 × ULN for subjects with bone or liver metastases); Renal Function: BUN ≤1.5 × ULN, SCr ≤1.5 × ULN. Normal cardiac function;
• Expected survival ≥12 weeks;
• Good compliance with follow-up;
• At least one measurable target lesion according to RECIST 1.1 criteria;
• Women of childbearing potential (aged 18-49) must have a negative pregnancy test within 7 days prior to the examination. Male and female patients of childbearing potential must agree to use effective contraception to prevent pregnancy during the study and for 3 months after the examination;
• Patients for whom the clinician recommends a PET/CT examination for tumor diagnosis and staging;
• Patients are fully capable of understanding the study, voluntarily agree to participate, and provide written informed consent.

Exclusion Criteria:

• Severe abnormalities in hepatic, renal, or hematological function;
• Patients planning for pregnancy;
• Pregnant or lactating women;
• Inability to lie flat for 30 minutes;
• Refusal to participate in this clinical study;
• Presence of claustrophobia or other psychiatric disorders;
• Any other condition deemed unsuitable for participation by the investigator.

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Condition: Clear Cell Renal Cell Cancer (ccRCC), Urothelial Carcinoma (UC), Colorectal Cancer, Cervical Cancer, Ovarian Cancer, Head and Neck Cancer, Hepatocellular Carcinoma (HCC), Cholangiocarcinoma, Non Small Cell Lung Cancer, Small Cell Lung Cancer, Breast Cancer, Pancreatic Cancer, Endometrial Cancer, Von Hippel Lindau Disease

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT07557225

Sponsor: Peking University First Hospital

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Inclusion Criteria:

1. All participants must meet the following criteria:
2. Written and voluntarily given Informed Consent.
3. Male or female ≥18 years of age at time of consent.
4. Have the capacity to understand the study and be willing and able to comply with all protocol requirements.
5. Participants with histologically confirmed or suspected tumors of the following types, but not limited to: Clear Cell Renal Cell Cancer; Urothelial Carcinoma; Colorectal Cancer; Cervical Cancer; Ovarian Cancer; Head and Neck Cancer; Hepatocellular Carcinoma; Cholangiocarcinoma; Non Small Cell Lung Cancer; Small Cell Lung Cancer; Breast Cancer; Pancreatic Cancer; Endometrial Cancer; Von Hippel Lindau Disease.

Exclusion Criteria:

1. Participants will be excluded from participation in the study if one or more of the following criteria are met:
2. Have any serious non-malignant disease (e.g., psychiatric, infectious, autoimmune or metabolic) that may interfere with the objectives of the study or with the safety or compliance of the participant, as judged by the Investigator.
3. Have a mental impairment that may compromise the ability to give Informed Consent and comply with the requirements of the study.
4. Be a female who is pregnant or breastfeeding.

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Condition: Kidney Cancers

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT07590310

Sponsor: Peking University Cancer Hospital & Institute

Phase: Early Phase 1

Eligibility:

• Age: minimum 18 Years maximum 75 Years
• Gender: All

Inclusion Criteria:

• -Hematological, hepatic, and renal functions meeting the following criteria: Complete Blood Count: WBC ≥4.0×10⁹/L or Neutrophils ≥1.5×10⁹/L, PLT ≥100×10⁹/L, Hb ≥90 g/L; Coagulation: PT or APTT ≤1.5 × ULN (Upper Limit of Normal); Hepatic Function: T-Bil ≤1.5 × ULN; ALT/AST ≤2.5 × ULN (or ≤5 × ULN for subjects with liver metastases); ALP ≤2.5 × ULN (or ≤4.5 × ULN for subjects with bone or liver metastases); Renal Function: BUN ≤1.5 × ULN, SCr ≤1.5 × ULN. Normal cardiac function;
• Expected survival ≥12 weeks;
• Good compliance with follow-up;
• At least one measurable target lesion according to RECIST 1.1 criteria;
• Women of childbearing potential (aged 18-49) must have a negative pregnancy test within 7 days prior to the examination. Male and female patients of childbearing potential must agree to use effective contraception to prevent pregnancy during the study and for 3 months after the examination;
• Patients for whom the clinician recommends a PET/CT examination for tumor diagnosis and staging;
• Patients are fully capable of understanding the study, voluntarily agree to participate, and provide written informed consent.

Exclusion Criteria:

• Severe abnormalities in hepatic, renal, or hematological function;
• Patients planning for pregnancy;
• Pregnant or lactating women;
• Inability to lie flat for 30 minutes;
• Refusal to participate in this clinical study;
• Presence of claustrophobia or other psychiatric disorders;
• Any other condition deemed unsuitable for participation by the investigator.

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Condition: Clear Cell RCC

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT07571551

Sponsor: Jinling Hospital, China

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum 80 Years
• Gender: All

Inclusion Criteria:

• Patients have fully understood and give written informed consent prior to receive neoadjuvant therapy. Patients with history of major psychiatric disease must be judged able to fully understand the trial, and the explicit consent of family members is required;
• Patients with the ages range from 18 to 80 years old (at the time of signing informed consent);
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1;
• Patients have at least 1 measurable target lesion according to RECIST v1.1. The target lesion can be biopsied as per protocol.
• Histologically confirmed clear cell RCC;
• Patients will be enrolled into 3 separate cohorts based on their clinical TNM at the time of baseline screening: 1. Cohort 1: localized ccRCC (cT1-2N0M0): the primary tumor in this cohort must meet the subsequent criteria:
• The cT1a primary tumor should have ≥10 R.E.N.A.L. score, or locate in renal hilum close to renal artery or its main branch;
• Patients with cT1b-2b primary tumors can be directly enrolled;
• In case of necessary, patients will undergo dual radiological examinations using contrast-enhanced CT and MRI to rule out potential invasion of the renal pelvis or perirenal fat as per protocol. 2. Cohort 2: locally advanced ccRCC (cT3-4N0M0 or cTanyN1M0); 3. Cohort 3: metastatic ccRCC (cTanyNanyM1): the patients should be evaluated as suitable for cytoreductive nephrectomy.
• Patient have no symptomatic metastatic lesions requiring urgent intervention;
• The sum of the diameters of the other target lesions (excluding the primary tumor) does not exceed the longest diameter of the primary tumor.
• The patients who are treatment-naive, and have not received systemic therapy for any tumor;
• Adequate main organ function. The screening laboratory indicators must meet the following criteria: 1. Hemoglobin ≥ 90 g/L (Without blood transfusion); 2. Platelets count ≥ 100 x 109/L; 3. Absolute neutrophil count ≥ 1.5 x 109/L; 4. Serum creatinine ≤ 1.5 x ULN, or eGFR > 60 mL/min/1.73m2; 5. Total bilirubin ≤ 1.5 mg/dL; 6. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 2.5 x ULN for patients without evidence of liver metastases; AST and/or ALT ≤ 5 x ULN for patients with liver metastases; 7. Normal CK; 8. Normal Troponin T; 9. Normal LDH.
• Willingness and ability to comply with planned visits, therapeutic laboratory testing, and other procedures.

Exclusion Criteria:

• Signs of tumor metastasis involving the central nervous system, or radiological evidence of brain metastasis;
• History of malignant tumors other than ccRCC within the previous 5 years, with the exception of malignant tumors that can be expected to be cured with treatment (including but not limited to adequately treated thyroid cancer, carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ of the breast treated with radical surgery);
• Prior to participating in the study, patients have received prior immune checkpoint inhibitors, investigational drugs or device therapy;
• History of undergoing major surgery (judged by the investigator) within 4 weeks before the first trial dose, are recovering, or are unable to undergo baseline puncture;
• History of severe drug allergy, including but not limited to antibody drugs;
• Patients with contraindications to immunotherapy restart, including but not limited to: 1. Grade 2-4 immune myocarditis; 2. Severe grade 4 proteinuria; 3. Severe or life-threatening grade 4 immune hepatitis; 4. Severe grade 3-4 immune pneumonitis; 5. Severe inflammatory arthritis that significantly affects daily life or quality of life; 6. Severe neurological toxicity: 7. Myasthenia gravis grade 2-4; 8. Guillain-Barre syndrome (GBS) or transverse myelitis of any grade; 9. Grade 2-4 encephalitis; 10. Severe or life-threatening grade 3-4 pancreatitis; 11. Severe or life-threatening bullous disease (grade 3-4); 12. Severe grade 3-4 uveitis or episcleritis.
• Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation or long-term corticosteroid therapy.
• Non-resolution of toxicity after previous antineoplastic therapy, i.e., resolution to baseline, CTCAE v5.0 grade 0-1 (excluding alopecia), or inclusion/exclusion criteria. Irreversible toxicities (e.g., hearing loss) that would not reasonably be expected to be exacerbated by the study drug can be included in the study;
• Known history of clinically significant liver disease, including active viral hepatitis (hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HbcAb) positive, HBV DNA>10000 copies /mL or >2000 IU/mL; Hepatitis C virus (HCV) antibody positive and HCV RNA positive), or other active hepatitis, clinically significant moderate to severe cirrhosis;
• Patients with uncontrolled third space effusion requiring repeated drainage, such as pleural effusion, ascites, pericardial effusion, etc. (Patients who do not need drainage of effusion or stop drainage for 3 days without significant increase in effusion can be enrolled);
• Receiving a systemic corticosteroid (prednisone > 10mg/ day or equivalent) or other immunosuppressive medication within 14 days before the first study medication;
• Patients with any severe and/or uncontrolled disease, including: 1. Hypertension that is not well controlled by antihypertensive medication; 2. Unstable angina pectoris or myocardial infarction, coronary artery bypass grafting or stent implantation within 6 months before study medication; 3. Grade I or above myocardial ischemia or myocardial infarction, arrhythmia (including QTc≥480ms) and ≥ grade 2 congestive heart failure (New York Heart Association (NYHA) classification); Degree II or above heart block; Left ventricular ejection fraction (LVEF) < 50%; 4. Poorly controlled diabetes (fasting blood glucose > 10 mmol/L); 5. Patients with urinary protein ≥++ and confirmed 24-hour urinary protein > 1.0g; 6. Severe active or uncontrolled infection.
• Patients with or suspected to have active autoimmune diseases, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, etc.;
• Renal failure requiring hemodialysis or peritoneal dialysis;
• Patients with a history of immunodeficiency, including HIV positive patients, other acquired immunodeficiency diseases, congenital immunodeficiency diseases, or organ transplantation history;
• History of live attenuated vaccine inoculation within 4 weeks before the first study drug or the expected vaccination during the study period;
• History of psychiatric drug abuse and can not quit or have a history of mental disorders;
• Women who are of childbearing potential. Women of childbearing potential must have a negative serum or urine pregnancy test, and must use appropriate methods of contraception.
• The presence of any other severe, acute or chronic medical disease or mental illness or laboratory abnormality, as judged by the investigator, that may increase the risk associated with participation in the study or that may interfere with the interpretation of the results of the study.

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Condition: Breast Cancer (Triple Negative Breast Cancer (TNBC)), Renal Cell Carcinoma (Kidney Cancer), Melanoma (Skin Cancer), Non-Small Cell Lung Cancer, MSI-H/dMMR Rectal Cancer, Squamous Cell Carcinoma Mouth, Invasive Mammary Carcinoma, Classic Hodgkin Lymphoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT07555210

Sponsor: Jessica Mezzanotte Sharpe

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Inclusion Criteria:

1. Age ≥ 18 years.
2. Patients planning to start or within the first four weeks of treatment with anti-PD-1 immune checkpoint inhibitor therapy either alone or in combination with chemotherapy for curative intent for a known cancer diagnosis (use of immunotherapy must be FDA-approved and not experimental).
3. Life expectancy of at least 12 months per the discretion of the treating physician.

Exclusion Criteria:

1. Patients ineligible for anti-PD-1 therapy.
2. Patients with metastatic disease.
3. Patients planning treatment with dual immune checkpoint inhibitor therapy.
4. Bony fractures in the pelvis, bilateral hips/femurs, thoracic spine, or lumbar spine.
5. Known osteoporosis or osteopenia.
6. Planned or previous treatment with denosumab, zoledronic acid, or other bisphosphonate therapy in the last six months.
7. Parathyroid gland disorders, rheumatoid arthritis (unless well-controlled off active biologic therapy without chronic steroid use), CKD stage IV/V, or ESRD.
8. Inability to comply with study procedures.
9. Inability to lie flat for 20-25 minutes during an imaging session.
10. Pregnant or breastfeeding patients.
11. Medical or psychiatric co-morbidities that, in the opinion of the treating physician, would prevent the patient from successfully participating in the study.

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Condition: Clear Cell Renal Cell Carcinoma, Sarcomatoid Renal Cell Carcinoma, Stage II Renal Cell Cancer AJCC v8, Stage III Renal Cell Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT07037004

Sponsor: City of Hope Medical Center

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Inclusion Criteria:

• Be willing and able to provide informed consent for the trial
• Histological confirmation of renal cell carcinoma (RCC) with a clear-cell or sarcomatoid component
• Pathologic stage of pT2, G4 or sarcomatoid, N0M0; pT3, any grade, N0M0; pT4, any grade, N0M0; pTany, any grade, N+M0; or M1 no evidence of disease (NED) after resection
• No prior systemic immunotherapy for RCC
• Eastern Cooperative Oncology Group (ECOG) performance status < 2
• Males and females, ages ≥ 18
• Any ethnicity or race
• Calculated creatinine clearance ≥ 30 milliliters per minute (mL/min) per the Cockcroft and Gault formula or serum creatinine < 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x ULN (< 5 x ULN if liver metastases are present)
• Total bilirubin < 1.5 x ULN (except subjects with Gilbert syndrome, who can have total bilirubin up to 3.0 mg/dL)
• Adequate bone marrow function defined by any of the following laboratory test findings: white blood cells (WBC) > 2,000/mm^3, neutrophils > 1,500/mm^3, platelets > 100,000/mm^3
• Female subjects of child-bearing potential and female partners of male subjects must agree to use a highly effective method of contraception during treatment and for at least 5 months after the last dose
• Highly effective methods of contraception include: tubal ligation, an approved hormonal contraceptive such as oral contraceptives, patches, implants, injections, rings or hormonally impregnated intrauterine device (IUD), or IUD

Exclusion Criteria:

• Prior radiation or anti-PD1, anti-PDL1, or anti-CTLA-4 therapy for RCC
• Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (> 10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll
• Active interstitial lung disease (ILD)/pneumonitis or history of ILD/pneumonitis requiring treatment with systemic steroids
• Baseline pulse oximetry less than 92% "on room air"
• Current use, or intent to use probiotics, prebiotics, yogurt, bacterial fortified foods and other natural supplements ≤ 2 weeks prior to treatment initiation and during the period of treatment
• Any condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• Uncontrolled adrenal insufficiency
• Known medical condition (e.g., a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results
• Not recovered to ≤ grade 1 toxicities related to any prior therapy before administration of study drug
• Women who are pregnant or breastfeeding
• History of myocarditis or congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), as well as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 6 months prior to study entry

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Condition: Renal Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05023265

Sponsor: Sunnybrook Health Sciences Centre

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Inclusion Criteria:

• Patients ≥18 years old
• Newly diagnosed RCC by biopsy (preferred) or radiologic evidence of growth on surveillance over two consecutive assessments (6-12 months)
• Primary lesion >3 cm, or recurrent lesion following local ablative therapy
• Medically inoperable or patient who refuses surgery following assessment by experienced urologist, and discussed in a multidisciplinary setting
• ECOG 0-2
• Written informed consent
• Participants must be able to understand the English-language or with the aid of a translator

Exclusion Criteria:

• Primary Lesion >20cm
• Evidence of distant metastatic disease
• Previous abdominal RT in vicinity of kidney preventing definitive SBRT
• History of major radiosensitivity syndrome
• Second invasive malignancy within the past 3 years (excluding non-melanomatous skin cancer)
• Currently pregnant or lactating

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Condition: Advanced or Metastatic Clear Cell Renal Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT07551349

Sponsor: Beijing Biotech

Phase: Phase 1/Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Inclusion Criteria:

• Written informed consent and willingness to comply with protocol procedures.
• Age >= 18 years at the time of consent.
• Histologically confirmed unresectable or metastatic clear cell RCC, or RCC with a clear-cell component, with radiographic progression after standard therapy.
• Prior exposure to at least one PD-1 / PD-L1-based regimen and at least one VEGF-pathway targeted regimen, or documented intolerance / unsuitability for available standard systemic options.
• At least one measurable lesion by RECIST 1.1.
• Available archival tumor tissue or willingness to undergo fresh biopsy for central biomarker testing; protocoldefined tumor positivity for CD70 and/or CAIX is required. Dual-positive cases are preferred for the biomarkerexpansion portion.
• ECOG performance status 0-1.
• Adequate marrow, liver, cardiac, pulmonary, and renal function as defined by the protocol (for example, ANC, platelets, bilirubin, AST/ALT, creatinine clearance, oxygen saturation, and left ventricular function within protocoldefined limits).
• Life expectancy of at least 12 weeks.
• Negative pregnancy test for participants of childbearing potential and agreement to highly effective contraception during protocol-defined risk windows.
• Previously treated brain metastases are allowed if clinically stable and off escalating corticosteroids for at least 14 days before lymphodepletion.

Exclusion Criteria:

• Active, untreated, or symptomatic central nervous system metastases, leptomeningeal disease, or uncontrolled seizure disorder.
• Prior gene-modified cellular therapy (including prior CAR-T, CAR-NK, CAR-NKT, or TCR-engineered therapy) within the protocol-defined washout window.
• Prior allogeneic stem cell transplant or solid organ transplant with ongoing clinically significant immunosuppression.
• Active autoimmune disease requiring systemic immunosuppressive treatment; physiologic replacement doses are permitted.
• Active uncontrolled infection, including uncontrolled hepatitis B, hepatitis C, HIV, tuberculosis, or sepsis.
• Clinically significant hepatobiliary disease that could increase risk from CAIX-directed therapy, such as active cholangitis, primary sclerosing cholangitis, biliary obstruction, Child-Pugh B/C cirrhosis, or prior hepatic venoocclusive disease.
• Clinically significant cardiovascular disease (for example, unstable angina, recent myocardial infarction, uncontrolled arrhythmia, or clinically meaningful heart failure).
• Systemic corticosteroid use greater than 10 mg prednisone equivalent daily within 7 days before lymphodepletion, unless required as physiologic replacement.
• Pregnancy or breastfeeding.
• Another active invasive malignancy requiring systemic treatment, except for protocol-defined low-risk exceptions.
• Known hypersensitivity to fludarabine, cyclophosphamide, or a critical study-product excipient.

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Condition: Type 2 Diabetes

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT07546929

Sponsor: Housey Healthcare ULC

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Key Inclusion Criteria:

• Have type 2 diabetes for greater than 3 months and no longer than 5 years by history prior to entering the trial, based upon ADA disease diagnostic criteria.
• Have an HbA1c > 6.5% and ≤ 10% as determined by the central lab at Visit 1 (Screening).
• Have been on a stable maximum dose of metformin for at least 3 months prior to entering the study or have been on stable therapy of diet and exercise only for at least 3 months. Stable treatment is defined as no change in treatment or dose in the last 3 months.

Key Exclusion Criteria:

• Have known type 1 diabetes.
• Diabetic complications
• Have taken any oral (other than metformin) or injectable treatment (insulin or GLP-1 RA classes or other) for type 2 diabetes currently or for greater than a 4 week duration previously. Previous treatment must have been stopped at least 3 months prior to screening
• Systolic blood pressure greater than 150 mmHg or a diastolic blood pressure greater than 100 mmHg at Visit 1 on average after three supine measurements, or a known history of renal artery stenosis.
• At baseline, the QT interval corrected by Fridericia (QTcF) ECG findings (>450 msec for males and >470 msec for females), left bundle branch block, or cardiac arrhythmia requiring medical or surgical treatment within 6 months prior to Visit 1 on the ECG.

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Condition: Radiation Therapy, Metastatic Renal Cancer, Recurrent Renal Cell Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT07540260

Sponsor: Peking University First Hospital

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Inclusion Criteria:

1. Adults (≥18 years) Histologically confirmed clear cell renal cell carcinoma Recurrent or metastatic disease Planned or ongoing first-line systemic therapy (targeted therapy plus anti-PD-1 immunotherapy) Dual PET/CT imaging available (FDG PET/CT and CAIX-targeted PET/CT) and eligible for radiotherapy planning Multidisciplinary assessment confirms radiotherapy is feasible to treat ≥75% of detectable lesions Able to provide written informed consent

Exclusion Criteria:

1. Unable to receive stereotactic radiotherapy as planned Uncontrolled serious comorbidities or active infection Pregnant or breastfeeding Unable or unwilling to comply with study procedures and follow-up

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Condition: Renal Cell Carcinoma (Kidney Cancer), Renal Cell Carcinoma (RCC), Tumor Thrombus, Prognosis, Prognostic Cancer Model, Real World Study, Observational Study

Study Type: Observational [Patient Registry]

Clinical Trials Identifier NCT 8-digits: NCT07117227

Sponsor: Peking University Third Hospital

Phase:

Eligibility:

• Age: minimum 18 Years maximum 80 Years
• Gender: All

Inclusion Criteria:

• Adults ≥18 years of age;
• Diagnosis of primary renal cell carcinoma before and during the surgery;
• Received radical nephrectomy/nephron-sparing surgery.

Exclusion Criteria:

• Subjects with severely missing clinical information;
• History of other malignant tumors.
• Recurrence observed before first postoperative follow-up.
• Discontinue the adjuvant treatment within in the first two course because of severe adverse react.

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Condition: Renal Cell Carcinoma (RCC)

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT07402109

Sponsor: Erasmus Medical Center

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Inclusion Criteria:

• Patients with histologically proven non-metastastic RCC or high suspicion of RCC based on imaging without histological evidence
• No metastatic lesions
• Patients must be 18 years or older
• Ability to understand the requirements of the study and to give written informed consent, as determined by the treating physician. Written informed consent

Exclusion Criteria:

• Previous high-dose radiotherapy in the region of the kidney

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Condition: Phase 1b, HC-7366, SHARK, Kidney Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT07401875

Sponsor: M.D. Anderson Cancer Center

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Eligibility Criteria:

• 1. Ability to understand and the willingness to sign a written informed consent document 2. Male or female ≥ 18 years of age 3. Confirmed diagnosis of clear cell RCC 4. Stage IV metastatic RCC per American Joint Committee on Cancer 5. Triplet Cohort (IO/IO): No prior systemic therapy for advanced RCC or prior adjuvant therapy allowed. 6. Doublet Cohort: Participant must have progressed on at least one PD1 based doublet regimen (IO/IO or IO/TKI). Prior adjuvant therapy is allowed and does count as one line of systemic therapy. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 ) 8. At least one measurable lesion as defined by RECIST 1.1 • A tumor lesion situated in a previously irradiated area is considered a measurable/target lesion only if subsequent disease progression has been documented in the lesion 9. Has pathology-confirmed RCC. Extra tissue should be submitted if available for correlatives. Formalin-fixed paraffin-embedded tissue blocks are preferred to slides. Details pertaining to tumor tissue submission can be found in the Lab Procedures Manual. 10. Willing and able to undergo bone and brain scans at baseline and continue to have scans performed if positive at screening. 11. Adequate organ function within 28 days prior to first dose of protocol-indicated treatment, including:
• White blood cell (WBC) ≥ 2,000 /μL
• Absolute neutrophil count (ANC) ≥ 1,000/μL
• Platelet count ≥ 100,000/μL
• Hemoglobin (Hgb) ≥ 9.0 g/dL in prior 4 weeks. Blood transfusions are allowed to achieve this.
• Serum creatinine ≤ upper limit of normal (ULN), or calculated creatinine clearance ≥ 30 mL/min (per the Cockcroft-Gault formula,)
• Total bilirubin ≤ ULN (except subjects with Gilbert Syndrome, who must have total bilirubin < 3.0 mg/dL)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN 12. Women must not be breastfeeding while taking the study drug and for up to five months after the last dose of study drug 13. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to receiving first dose of protocol-indicated treatment
• "Women of childbearing potential" (WOCBP) is defined as any female who has experienced menarche who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or is not postmenopausal
• Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 years of age in the absence of other biological or physiological causes
• If menopausal status is considered for the purpose of evaluating childbearing potential, women < 62 years of age must have a documented serum follicle stimulating hormone (FSH) level within laboratory reference range for postmenopausal women, in order to be considered postmenopausal and not of childbearing potential 14. Women of childbearing potential (WOCBP) must agree to follow instructions for acceptable contraception prior to the study and from the time of signing consent, for the duration of the study participation and for 23 weeks after their last dose of protocol-indicated treatment
• The effects of HC-7366 on the developing human fetus are unknown. For this reason and because first-in-class, first-in-human agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114).
• Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the study and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. 15. Men not azoospermic who are sexually active with WOCBP must agree to follow instructions for acceptable contraception prior to the study and from the time of signing consent, for the duration of the study participation, and for 31 weeks after their last dose of protocol-indicated treatment 16. Participant s with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated 17. Participant s with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load 18. Participant s with previously treated brain metastases may be eligible provided they are radiologically (by MRI) and clinically stable (i.e., without evidence of disease progression) for at least 4 weeks (28 days) by repeat imaging (repeat imaging should be performed during study screening), with no evidence of new or enlarging brain metastases, and without requirement for steroid treatment for at least 28 days prior to the first dose of study drug or study therapy. (CT is acceptable if MRI is contraindicated) 19. Participant s with a prior or concurrent malignancy whose natural history or treatment does not interfere with the safety or efficacy assessment of the investigational regimen are eligible for this study 20. Participant s with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this study, participant s should be class 2B or better

Exclusion Criteria:

• 1. For the Triplet Cohort (Nivo/Ipi/HC-7366):
• Prior systemic treatment including neoadjuvant or adjuvant therapy including an immune checkpoint inhibitor or TKI 2. For the Doublet Cohort (Nivo/HC-7366):
• More than 3 prior lines of systemic therapy allowed
• Has received any type of small molecule kinase inhibitor (including investigational kinase inhibitor) ≤ 2 weeks before start of study drug or study therapy 3. ≤ 28 days before first dose of protocol-indicated treatment:
• Major surgery requiring general anesthesia 4. ≤ 14 days before first dose of protocol-indicated treatment:
• Radiosurgery or radiotherapy
• Minor surgery. (Note: Placement of a vascular access device is not considered minor or major surgery)
• Active infection requiring systemic treatment 5. Known or suspected clinically significant active bleeding including active hemoptysis 6. Inability to swallow oral medication; or the presence of a poorly controlled gastrointestinal disorder that could significantly affect the absorption of oral study drug
• e.g. Crohn's disease, ulcerative colitis, chronic diarrhea (defined as > 4 loose stools per day), malabsorption, or bowel obstruction 7. Central nervous system (CNS) metastasis, unless asymptomatic and radiologically (by MRI) and clinically stable (i.e., without evidence of disease progression) for at least 4 weeks (28 days) by repeat imaging (repeat imaging should be performed during study screening), with no evidence of new or enlarging brain metastases, and without requirement for steroid treatment for at least 28 days prior to the first dose of study drug or study therapy. (CT is acceptable if MRI is contraindicated 8. Any condition requiring systemic treatment with either corticosteroids (> 10 mg/day prednisone or equivalent daily) or other immunosuppressive medications within 14 days prior to initiating protocol-indicated treatment
• In the absence of active autoimmune disease: Subjects are permitted the use of corticosteroids with minimal systemic absorption (e.g. topical, ocular, intraarticular, intranasal, and inhalational) ≤ 10 mg/day prednisone or equivalent daily; and physiologic replacement doses of systemic corticosteroids ≤ 10 mg/day prednisone or equivalent daily (e.g. hormone replacement therapy needed in participants with hypophysitis) 9. Active, known or suspected autoimmune disease
• Subjects with type I diabetes mellitus; hypothyroidism only requiring hormone replacement; skin disorders such as vitiligo, psoriasis or alopecia not requiring systemic treatment; or conditions not expected by the investigator to recur in the absence of an external trigger are permitted to enroll 10. Known psychiatric condition, social circumstance, or other medical condition reasonably judged by the investigator to unacceptably increase the risk of study participation; or to prohibit the understanding or rendering of informed consent or anticipated compliance with and interpretation of scheduled visits, treatment schedule, laboratory tests and other study requirements 11. Pregnant women are excluded from this study because HC-7366 is novel, first-in-class small molecule agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with HC-7366, breastfeeding should be discontinued if the mother is treated with HC-7366. These potential risks may also apply to other agents used in this study 12. Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this study 13. Participants who are receiving any other investigational agents

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Condition: Renal Cell Carcinoma, Kidney Cancer, Kidney Neoplasm, Renal Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT07397611

Sponsor: Dana-Farber Cancer Institute

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Inclusion Criteria:

• Adult patients age ≥ 18 years.
• Histologically confirmed diagnosis of ccRCC by a core-needle biopsy. Patients who have not had prior biopsy may undergo screening if they have suspected RCC but can only proceed to registration if ccRCC (any component) is confirmed on the pre-treatment study biopsy.
• Stage cT2 RCC with grade 4 or sarcomatoid features, ≥cT3 Nx RCC, or cTany N+ RCC disease for which partial or radical nephrectomy is planned. For clinical staging, a kidney MRI is highly preferred over a CT Abdomen.
• Participants must have measurable disease i.e. a primary renal tumor that can be accurately measured in at least one dimension as ≥10 mm (≥1 cm) with CT scan or MRI. See Section 11 (Measurement of Effect) for the evaluation of measurable disease.
• Participants must be planned for surgical resection of their primary renal tumor.
• ECOG performance status of 0-1.
• Participants must have adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days before first dose of study treatment: 1. Absolute neutrophil count ≥ 1.0 × 10^9/L without granulocyte colony-stimulating factor support within 2 weeks of screening laboratory sample collection. 2. Platelet count ≥ 100 × 10^9/L without transfusion within 2 weeks of screening laboratory sample collection. 3. Hemoglobin ≥ 10.0 g/dL (or 6.2 mmol/L). 4. Aspartate transaminase (AST) ≤ 2.5 × upper limit of normal (ULN) 5. Alanine aminotransferase (ALT) ≤ 2.5 × ULN. 6. Bilirubin ≤ 1.5 × ULN (except participants with Gilbert syndrome who must have total bilirubin < 3.0 mg/dL). 7. Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN. 8. Ambulatory oxygen saturation >92% on room air at time of screening. 9. Serum albumin ≥ 2.8 g/dl. 10. INR ≤ 1.5. 11. Calculated creatinine clearance ≥ 40 mL/min (≥ 0.67 mL/sec) using the Cockcroft-Gault equation: ---Males: (140
• age) x weight (kg)/(serum creatinine [mg/dL] × 72) ---Females: [(140
• age) x weight (kg)/(serum creatinine [mg/dL] × 72)] × 0.85
• No exercise-induced desaturation on a 6-minute walk test, defined as a blood oxygen saturation by pulse oximetry ≤ 88%.
• No active clinical pneumonitis at screening.
• No medical history of severe chronic obstructive pulmonary disease (COPD)
• Screening echocardiogram or MUGA scan must demonstrate a left ventricular ejection fraction (LVEF) greater than the institutional lower limit of normal (LLN).
• Negative serum pregnancy test at screening for women of childbearing potential. Female subjects are considered to be of childbearing potential unless one of the following criteria is met: permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman > 45 years-of-age in the absence of other biological or physiological causes. In addition, females < 55 years-of-age must have a serum follicle stimulating hormone [FSH] level > 40 mIU/mL to confirm menopause). Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff.
• Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception during the course of the study and for the following durations after the last dose of treatment (whichever is later). An additional contraceptive method, such as a barrier method (eg, condom), is required. In addition, men must agree not to donate sperm and women must agree not to donate eggs (ova, oocyte) for the purpose of reproduction during these same periods. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• Through 7 days after the last dose of casdatifan and 120 days after the last dose of zimberelimab for women of childbearing potential and for men
• Ability to understand and the willingness to sign a written informed consent document.
• Ability to swallow tablets.

Exclusion Criteria:

• Any prior systemic therapy for treatment of renal cell carcinoma.
• Any radiation therapy within 4 weeks before the first dose of study treatment.
• Any clear evidence of distant metastases. Enlarged lymph nodes that are planned to be removed during nephrectomy are permitted.
• Clinical pneumonitis or concern for inflammatory lung disease at time of screening.
• Any complementary medications (eg, herbal supplements or traditional Chinese medicines) with the intention to treat the disease under study within 2 weeks before first dose of study treatment.
• Other prior malignancy active within the previous year except for locally curable cancers (>90%) that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast, or Gleason 6 prostate cancer. Also, indolent malignancies, including but not limited to early-stage chronic lymphocytic leukemia and follicular lymphoma, that don't require anti-cancer treatment, could be allowed after discussion with the medical monitor.
• QTc ≥ 480 msec using Fridericia's correction (QTcF) (based on an average of triplicate recordings).
• Malabsorption condition that would alter the absorption of orally administered medications.
• Patient has had any major cardiovascular event within 6 months prior to study drug administration including but not limited to myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic event, pulmonary embolism, clinically significant ventricular arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes) or New York Heart Association Class III or IV heart failure.
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: a. Cardiovascular disorders: i. Congestive heart failure New York Heart Association Class 2 or greater, unstable angina pectoris, serious cardiac arrhythmias (eg, ventricular flutter, ventricular fibrillation, Torsades de pointes). ii. Uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 95 mm Hg diastolic despite optimal antihypertensive treatment. iii. Any history of stroke (including transient ischemic attack [TIA]), myocardial infarction, or other clinically significant ischemic event within 12 months before first dose of study treatment. iv. Clinically significant pulmonary embolism (PE) or deep vein thrombosis (DVT) or prior clinically significant venous or non-CVA/TIA arterial thromboembolic events within 3 months before to first dose of study treatment. Thrombus felt due to tumor and not a bland thrombus is permitted. Note: Subjects with a diagnosis of DVT/PE due to bland thrombus need to be asymptomatic and have at least 4 weeks of anticoagulation before first dose of study treatment. v. Any history of myocarditis. b. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation: i. Tumors invading the GI-tract from external viscera. ii. Active and symptomatic peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or acute pancreatitis. iii. Acute obstruction of the bowel, gastric outlet, or pancreatic or biliary duct within 6 months unless the cause of obstruction is definitively managed and subject is asymptomatic. iv. Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 6 months before the first dose. Note: Complete healing of an intra-abdominal abscess must be confirmed before the first dose of study treatment. v. Known gastric or esophageal varices. vi. Ascites requiring drainage within 28 days prior to initiation of protocol therapy c. Autoimmune disease that has been symptomatic or required treatment with 1mg/kg of corticosteroids within the past two years from the date of randomization. Diabetes mellitus and thyroid auto-immune diseases are excluded. d. Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Note: Inhaled, intranasal, intra-articular, or topical steroids are permitted. Adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted. Transient short-term use of systemic corticosteroids for allergic conditions (eg, contrast allergy) is also allowed. Corticosteroids given as short course premedication is acceptable.
• Other clinically significant disorders that would preclude safe study participation. 1. Active infection requiring systemic treatment. Note: Prophylactic antibiotic treatment is allowed. 2. Infection with acute or chronic hepatitis B or C with detectable viral load, human immunodeficiency virus (HIV) infection with detectable viral load or acquired immunodeficiency syndrome (AIDS)-related illness. 3. Serious non-healing wound/ulcer/bone fracture. Note: non-healing wounds or ulcers are permitted if due to tumor-associated skin lesions. 4. Pharmacologically uncompensated, symptomatic hypothyroidism. 5. Moderate to severe hepatic impairment (Child-Pugh B or C). 6. History of solid organ or allogeneic stem cell transplant.
• Major surgery (as defined in Appendix B) within 4 weeks prior to first dose of study treatment. Minor surgery (eg, simple excision, tooth extraction) within 7 days before the first dose of study treatment. Complete wound healing from major or minor surgery must have occurred at least prior to the first dose of study treatment.
• Patients who are receiving treatment with strong CYP3A4 inhibitors and inducers should have a washout period of 28 days or 5 half-lives of the concerning medicine prior to starting casdatifan.
• History of psychiatric illness, mental condition or substance use disorders that are likely to interfere with ability to comply with protocol requirements or give informed consent.
• Use of any live vaccines against infectious diseases within 28 days of first dose of study drug.
• Current breastfeeding.
• Previously identified allergy or hypersensitivity to components of the study treatment formulations.
• Any use of supplemental or intermittent oxygen therapy.
• Other conditions, which in the opinion of the Investigator, would compromise the safety of the patient or the patient's ability to complete the study.

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Condition: Kidney Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06882486

Sponsor: Institut Paoli-Calmettes

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Inclusion Criteria:

1. Patient aged ≥ 18 years
2. Diagnosed with synchronous metastatic kidney cancer
3. With primary tumor still in place (no primary cytoreductive nephrectomy)
4. Having received systemic ICI immunotherapy-based combination therapy
5. In CR or mPR (defined as >75% response in metastatic lesions from baseline) according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1), excluding the primary renal lesion.
6. Signed consent to participate
7. Affiliated to the national social security scheme or beneficiaries of such a scheme

Exclusion Criteria:

1. Women who are or may become pregnant (without effective contraception) or who are breast-feeding.
2. Person in an emergency situation or unable to give consent.
3. An adult under legal protection (guardianship, curators or safeguard of justice),
4. Inability to undergo medical follow-up for geographical, social or psychological reasons.
5. Patients who have undergone prior cytoreductive nephrectomy
6. Patients considering nephrectomy for symptomatic disease, but without major response (CR or mPR) in metastatic disease
7. Patients with non-metastatic disease at diagnosis who have received ICI in a neo-adjuvant setting
8. Patients with contraindications to surgery or ineligible for nephrectomy
9. Patients not wishing to undergo nephrectomy
10. Patients with end-stage renal disease

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Condition: Clear Cell Renal Cell Carcinoma, Neoplasms, Malignant Neoplasms, Malignant Neoplasm of Kidney, Except Renal Pelvis

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT07469683

Sponsor: Yonsei University

Phase: Phase 2

Eligibility:

• Age: minimum 19 Years maximum N/A
• Gender: All

Inclusion Criteria:

• 1. Histologically or cytologically confirmed diagnosis of locally advanced or metastatic ccRCC. 1. Part 1 (Safety Run-in): At least one first-line treatment of standard of care in the recurrent/metastatic setting. 2. Part 2 (Phase 2): Anti-PD-1 (Programmed Cell Death Protein 1) or anti-PD-L1 (Programmed Cell Death-Ligand 1) monotherapy or combination therapy as first-line treatment in the recurrent/metastatic setting. 2. At least one measurable lesion as defined by RECIST (Response Evaluation Criteria in Solid Tumors) v1.1. 3. Male or female patients aged ≥ 19 years at the date on which the informed consent is signed. 4. Ability and willingness to provide written informed consent and to comply with all study procedures. 5. Estimated life expectancy of ≥ 3 months. 6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. 7. Adequate organ functions as defined below. System organ class Laboratory test results
• Hematology : Absolute neutrophil count (ANC) ≥ 1500 cells/μL without the support of granulocyte colony-stimulating factor (G-CSF) within 2 weeks prior to the first dose of the study intervention. Platelet count ≥ 100,000/μL without the support of transfusion within 2 weeks prior to screening laboratory sample collection. Hemoglobin ≥ 9 g/dL without the support of transfusion within 2 weeks prior to screening laboratory sample collection.
• Coagulation :International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 × the upper limit of normal (ULN). If the patient is receiving anticoagulant therapy, PT shall be within the therapeutic range for the intended use of anticoagulants.
• Kidney :Estimated glomerular filtration rate (eGFR) calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. ≥ 40 mL/min/1.73 m2
• Liver :Total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN for patients with Gilbert's syndrome), or if total bilirubin is > 1.5 × ULN, direct bilirubin ≤ ULN. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN for patients with documented liver metastases). Albumin ≥ 2.8 g/dL 8. If there were any clinically significant toxicities from prior therapies, they shall have resolved to Grade 0 or Grade 1 according to the NCI CTCAE v5.0 (Alopecia and ≤ Grade 2 endocrine-related adverse events related to prior immunotherapy (e.g., immune checkpoint inhibitors) that require medical treatment or hormone replacement therapy are considered acceptable for study participation.). 9. Male and female patients of childbearing potential shall agree to use existing, highly effective contraception methods with the failure rate of <1% (Appendix 1) during the treatment period and for 3 months after the last administration of the study intervention. Acceptable methods shall include barrier methods such as spermicide condoms or diaphragms. Women of childbearing potential (WOCBP) are defined as females who have experienced menarche and are not postmenopausal (including amenorrhea for at least 2 years without hormone therapy or surgical sterilization). 10. WOCBP shall have a documented negative serum or urine pregnancy test at screening, performed within 3 days prior to the first administration of the study intervention. For non-childbearing females, one of the following shall be documented: 1. Postmenopausal status, defined as the absence of regular menstruation for at least 12 consecutive months with a documented serum follicle-stimulating hormone (FSH) level within the laboratory reference range for postmenopausal women, or 2. Documented history of hysterectomy or bilateral oophorectomy, or 3. Medically confirmed ovarian failure.

Exclusion Criteria:

1. History of malignancy or active malignancy other than the target disease in this study. Exceptions are as follows:
2. Malignancies that have been treated with curative intent and have not recurred within the recent 2 years.
3. Completely resected basal cell carcinoma or squamous cell carcinoma of the skin.
4. Any type of completely resected carcinoma in situ.
5. Known brain metastases or epidural conditions. However, patients who have been sufficiently treated with radiotherapy and/or surgery (including radiosurgery) and have been stable for at least 4 weeks prior to the first administration of the study intervention can be enrolled. Note: Patients with an incidental finding of a single lesion <1 cm may be eligible if deemed not to require treatment at the discretion of the investigator. Eligible patients shall be neurologically asymptomatic and shall not have received corticosteroid therapy for at least 2 weeks prior to the first administration of the study intervention.
6. Diagnosis of immunodeficiency or current use of chronic systemic corticosteroids or other immunosuppressive therapy within 7 days prior to the first administration of the study intervention. Topical (< Grade III), inhaled corticosteroids, or intra-articular corticosteroids, topical creams/lotions, mouthwashes containing corticosteroids, or mineralocorticoids (e.g., fludrocortisone) are allowed. Note: Chronic use of ≤ 10 mg/day of prednisone or equivalent may be allowed after discussion and approval by the lead institution.
7. Active autoimmune disease that has required systemic treatment (e.g., disease controllers, corticosteroids, or immunosuppressive drugs) within the recent 2 years. Replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroids for adrenal insufficiency or hypopituitarism) is not considered a form of systemic treatment.
8. Known infection with Human Immunodeficiency Virus-1 (HIV-1) or HIV-
9. Known active hepatitis B virus infection (i.e., HBsAg positive) or hepatitis C virus infection (e.g., [qualitatively] detectable HCV RNA). Patients with a negative HCV RNA test after a positive HCV antibody test and no ongoing anti-HCV therapy.
10. Active infection requiring systemic therapy.
11. Significant cardiovascular diseases, including but not limited to: Stable arrhythmias medically controlled with ongoing medication are allowed.
12. QT interval (Interval from the start of the Q wave to the end of the T wave of the ECG) corrected for heart rate using Fridericia's formula (QTcF) > 480 msec at screening
13. Myocardial infarction, acute coronary syndrome, or history of coronary angioplasty/stenting/bypass grafting within the recent 6 months.
14. Congestive heart failure (CHF) classified as New York Heart Association (NYHA) Class II-IV, or a history of NYHA Class III or IV CHF.
15. Patients with significant respiratory symptoms, known or suspected serious or severe pulmonary conditions at screening, or requiring supplemental oxygen.
16. Any form of systemic anticancer therapy (including investigational therapy) within 3 weeks prior to the first administration of the study intervention, or within 5 half-lives of the drug if known, whichever is shorter.
17. Participation in an interventional clinical trial involving an investigational drug or device within 3 weeks prior to the first administration of the study intervention in this clinical trial. Patients who are participating in follow-up may be enrolled if more than 3 weeks have passed since the last administration.
18. Radiotherapy within 2 weeks prior to the first administration of the study intervention. Patients with ongoing clinically related complications from prior radiotherapy are not eligible.
19. Major surgery within 2 weeks prior to administration of the study intervention. Patients shall have sufficiently recovered from any toxicity and/or complications at the discretion of the investigator.
20. Live vaccine administration within 4 weeks prior to the first administration of the study intervention. Administration of non-live COVID-19 vaccines within 7 days prior to the DLT assessment is contraindicated, as vaccine-related toxicity may interfere with safety assessments.
21. Prior therapy using IL-2 (interleukin-2)-based drugs.
22. History of prior axitinib treatment.
23. Inability to swallow oral drugs or presence of gastrointestinal disorders that may affect absorption (e.g., gastrectomy, partial bowel obstruction, or malabsorption syndrome).
24. Current administration of potent CYP3A4 inducers (e.g., mitotane, phenytoin, rifampin, carbamazepine, or St. John's Wort) that cannot be discontinued during the study.
25. Current administration of potent CYP3A4 inhibitors (e.g., boceprevir, cobicistat, itraconazole, ketoconazole, clarithromycin, idelalisib, nefazodone, nelfinavir, and ritonavir co-administered with protease inhibitors) that cannot be discontinued during the study.
26. Medically significant bleeding within 3 months prior to randomization. Tumor invasion/infiltration of major blood vessels shall be evaluated, and the potential risk of severe hemorrhage due to tumor shrinkage or necrosis will be considered as part of the exclusion assessment.
27. Ongoing concomitant treatment at a therapeutic dose with anticoagulants such as heparin, thrombin, or factor Xa inhibitors, or with antiplatelet agents (e.g., clopidogrel).
28. Low-dose aspirin (≤ 100 mg/day), prophylactic low molecular weight heparin (LMWH), and prophylactic factor Xa inhibitors are acceptable.
29. Anticoagulation therapy with LMWH at a therapeutic dose is allowed in participants who have no radiologic evidence of uncontrolled brain metastases, have been on a stable dose of LMWH for at least 2 weeks prior to randomization, and have no history of thromboembolic complications or complications from anticoagulation therapy.
30. Presence of the following clinically significant diseases:
31. Unhealed serious active wounds, ulcers, or fractures
32. Requirement for hemodialysis or peritoneal dialysis.
33. History of solid organ transplantation.
34. Ascites with symptoms requiring medical intervention.
35. Known hypersensitivity to any component of the study intervention (SLC-3010 or axitinib), or their analogs.
36. Any condition, therapy, laboratory abnormality, or other circumstance (medical history or current evidence) that may expose the patient to risk by participating in the clinical trial, cause confusion in study results, or interfere with the patient's participation throughout the study.
37. Psychiatric or substance abuse disorders known to interfere with compliance with study requirements.
38. For female patients only: Pregnant or breastfeeding.

View trial on ClinicalTrials.gov

Condition: Renal Tumors

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT06868927

Sponsor: IRCCS San Raffaele

Phase:

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Inclusion Criteria:

• Presence of a renal mass up to 4 cm
• Adult > 18 years
• Candidate to renal surgery
• Informed consent signed

Exclusion Criteria:

• Contraindication for MRI

View trial on ClinicalTrials.gov