Bladder Cancer

Condition: Non Muscle Invasive Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06972615

Sponsor: BLATAM

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

• 1. Be willing and able to provide documented informed consent for the trial. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research. 2. Be ≥18 years of age on the day of signing informed consent. 3. Have a histologically confirmed diagnosis of high-risk non-muscle invasive (T1, High Grade Ta and/or CIS) transitional cell carcinoma of the bladder. Subjects with tumors of mixed transitional/non-transitional cell histology are allowed, but transitional cell carcinoma must be the predominant histology. Subjects with predominant or exclusively non-transitional cell histology are not allowed. Confirmation of histology, grade and stage will be performed by central review and must be completed during the screening period and prior to enrollment. 4. In subjects who have papillary tumors (Ta and T1), a complete TURBT must have been performed, as characterized by:Attainment of a visually complete resection of all papillary tumors (Ta and T1) 5- Have been treated with adequate BCG therapy and have developed high risk NMIBC that is unresponsive or exposed to BCG therapy. Adequate BCG therapy must include:
• An induction course with at least 5 out of 6 BCG instillations (adequate induction); and
• At least 7 out of 9 BCG instillations within 9 months of the first instillation of adequate induction therapy BCG unresponsive high risk NMIBC is defined as:
• Stage progression at 3 months (±4 weeks) despite adequate induction therapy (e.g., Ta to T1, or CIS to T1; note: adequate induction therapy only, defined above, is required in this case); or
• High grade T1 disease at the first evaluation after adequate BCG induction or
• Persistent high risk NMIBC at 6 months (±4 weeks) after adequate BCG; or
• Recurrent high risk NMIBC within 12 months of the last BCG instillation despite having received adequate BCG. BCG Exposed is defined as: having high-grade persistent (BCG resistant) or recurrent NMIBC within 24 months of the last BCG dose but not meeting the definition of BCG-unresponsive

Exclusion Criteria:

• 1. Has muscle-invasive (i.e. T2, T3, T4) locally advanced non-resectable or metastatic urothelial carcinoma. 2. Has concurrent extra-vesical (i.e. urethra, ureter or renal pelvis) non-muscle-invasive transitional cell carcinoma of the urothelium. 3. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. 4. Has undergone any intervening intravesical chemotherapy or immunotherapy from the time of most recent cystoscopy/ transurethral resection of bladder tumor to starting trial treatment. (Note: A single dose of intravesical treatment given as part of the most recent cystoscopy/ transurethral resection of bladder tumor, during the screening period, such as with chemotherapy as per local/regional practices, is acceptable.) 5. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to Cycle 1, Day 1 or who has not recovered (ie, ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent

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Condition: Urothelial Carcinoma (UC), Upper Tract Urothelial Carcinoma, UTUC, Bladder Cancer (BC)

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT07614594

Sponsor: Henan Provincial People's Hospital

Phase:

Eligibility:

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

Inclusion Criteria:

1. Patients are eligible if they meet all of the following criteria:
2. Age ≥ 18 years.
3. Presence of gross or microscopic hematuria.
4. Imaging (B-ultrasonography, CT, or MRI) showing a renal pelvic, ureteral, or bladder lesion.
5. Scheduled for surgery for tissue histopathological diagnosis.
6. Able to provide written informed consent.

Exclusion Criteria:

1. Inadequate urine sample (poor quality or insufficient volume).
2. Lack of final histopathological diagnosis.

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Condition: Bladder Cancer, Urothelial Carcinoma (UC), Muscle Invasive Bladder Cancer (MIBC), Non Muscle Invasive Bladder Cancer

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT07602010

Sponsor: Oslo University Hospital

Phase:

Eligibility:

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

Inclusion Criteria:

• Age ≥ 18 years
• Newly diagnosed bladder cancer on cystoscopy
• Planned TURBT or cystectomy within 6 weeks
• Eligible for both CT and MRI within 6 weeks
• Written informed consent provided

Exclusion Criteria:

• Contraindications to MRI or iodinated contrast media
• Prior treatment for bladder cancer
• Pregnancy
• Non-malignant bladder lesions
• Tumors located in bladder diverticula

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Condition: Bladder (Urothelial, Transitional Cell) Cancer, Bladder Cancer Recurrence, Progression of Bladder Cancer, Transurethral Resection of Bladder Tumor, Urothelial Carcinoma of the Bladder

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT07589413

Sponsor: Zhiping Wang

Phase:

Eligibility:

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

Inclusion Criteria:

1. Age 18 years or older.
2. Suspected or histologically confirmed urothelial carcinoma of the bladder.
3. Scheduled to undergo TURBT.
4. Availability of sufficient peripheral blood samples for cfDNA extraction and mutation analysis.
5. Availability of complete clinicopathological and perioperative data.
6. Ability to provide informed consent and comply with study follow-up.

Exclusion Criteria:

1. Non-urothelial bladder malignancy confirmed by pathology.
2. History of other malignant tumors within the past 5 years, except adequately treated non-melanoma skin cancer or carcinoma in situ of the cervix.
3. Previous radical cystectomy or systemic antitumor therapy before enrollment.
4. Inadequate blood sample quality or insufficient DNA yield for mutation analysis.
5. Pregnancy or breastfeeding.
6. Serious uncontrolled intercurrent illness that may interfere with study participation, follow-up, or compliance, including active infection, symptomatic congestive heart failure, unstable angina, clinically significant arrhythmia, severe psychiatric illness, or other conditions judged by the investigator to make participation unsuitable.

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Condition: Bladder (Urothelial, Transitional Cell) Cancer, Bladder Cancer Recurrence, Progression of Bladder Cancer, Transurethral Resection of Bladder Tumor, Urothelial Carcinoma of the Bladder

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT07589413

Sponsor: Zhiping Wang

Phase:

Eligibility:

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

Inclusion Criteria:

1. Age 18 years or older.
2. Suspected or histologically confirmed urothelial carcinoma of the bladder.
3. Scheduled to undergo TURBT.
4. Availability of sufficient peripheral blood samples for cfDNA extraction and mutation analysis.
5. Availability of complete clinicopathological and perioperative data.
6. Ability to provide informed consent and comply with study follow-up.

Exclusion Criteria:

1. Non-urothelial bladder malignancy confirmed by pathology.
2. History of other malignant tumors within the past 5 years, except adequately treated non-melanoma skin cancer or carcinoma in situ of the cervix.
3. Previous radical cystectomy or systemic antitumor therapy before enrollment.
4. Inadequate blood sample quality or insufficient DNA yield for mutation analysis.
5. Pregnancy or breastfeeding.
6. Serious uncontrolled intercurrent illness that may interfere with study participation, follow-up, or compliance, including active infection, symptomatic congestive heart failure, unstable angina, clinically significant arrhythmia, severe psychiatric illness, or other conditions judged by the investigator to make participation unsuitable.

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Condition: Low Grade Upper Tract Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT07265947

Sponsor: Tyra Biosciences, Inc

Phase: Phase 2

Eligibility:

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

Exclusion Criteria:

1. Evidence or any features of high grade (HG) UTUC
2. History of carcinoma in situ (CIS)
3. History of prostatic urethral involvement
4. Current or previous history of muscle invasive bladder cancer
5. Current or previous history of lymph node positive and/or metastatic bladder cancer
6. Evidence of squamous cell carcinoma, adenocarcinoma or undifferentiated carcinoma or small cell of the bladder
7. Currently receiving systemic cancer therapy (cytotoxic or immunotherapy)
8. Current or prior history of pelvic external beam radiotherapy for bladder cancer
9. Current or history of receiving a prior FGFR inhibitor
10. Systemic immunotherapy within 6 months prior to randomization
11. Treatment with an investigational agent within 30 days or 5 half-lives from randomization, whichever is shorter; compounds with an unknown half-life will be default to 30 days.
12. Prior treatment with an intravesical or intracavitary agent within 8 weeks of C1D
13. Current evidence of central serous retinopathy or retinal pigmented epithelial detachment of any grade at time of baseline examination.
14. Requiring use of medications that are potential inhibitors or inducers of CYP3A (prohibited list of medications)

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Condition: Bladder Cancer

Study Type: Observational [Patient Registry]

Clinical Trials Identifier NCT 8-digits: NCT07581496

Sponsor: University Hospital, Basel, Switzerland

Phase:

Eligibility:

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

Inclusion Criteria:

1. All patients > 18 years of age, able to give informed consent as documented by signature, with a cystoscopically proven bladder cancer, suspicious for T1 stage, estimated by the treating physician, who will undergo TUR-B

Exclusion Criteria:

1. Patients with metastases or concomitant upper tract tumor at diagnosis will be excluded, Patients with non T1 G3 cancers will be excluded from the study and no further sampling and analyses will take place. Patients with upstaging, either at re-TUR-B or after immediate radical cystectomy will be excluded for further ct-DNA sampling, Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. Vulnerable persons (e.g. < 18y of age, unable to consent to the study)

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Condition: Urothelial Cancer, Urinary Bladder Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT07566156

Sponsor: Astellas Pharma Global Development, Inc.

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

• Has histologically confirmed initial diagnosis of muscle-invasive bladder cancer (MIBC) with predominant urothelial histology staged cT2-T4aN0M0
• Tissue comprising muscle-invasive urothelial cancer must be submitted for clinical staging at baseline
• Eligible for and agree to receive chemoradiotherapy and one of the protocol-specified radiosensitizing chemotherapy regimens
• Fit for systemic therapy and elect bladder preservation, including participants who are ineligible for or have elected not to undergo cystectomy
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

Exclusion Criteria:

• Advanced or metastatic disease (N+, M1), non-urothelial carcinoma, diffuse or multifocal CIS, urothelial carcinoma or histological variant at any site outside the urinary bladder within previous 24 months prior to randomization except Ta/T1/CIS of the upper urinary tract including renal pelvis and ureter if the participant had undergone complete nephrectomy
• Has received any prior systemic treatment, chemoradiation, and/or radiation for MIBC or NMIBC
• Prior pelvic radiation for any reason
• Inadequate bladder function
• Other active malignancies within 3 years prior to randomization
• Previously treated with enfortumab vedotin or other MMAE-based antibody-drug conjugates (ADCs)
• Previously treated with a PD(L)-1 inhibitor, defined as a PD-1 inhibitor or PD-L1 inhibitor
• Uncontrolled diabetes
• Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of randomization. Routine antimicrobial prophylaxis is permitted
• Known active hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV) infection
• Received major surgery (defined as requiring general anesthesia and >24 hour inpatient hospitalization) within 4 weeks prior to randomization
• Known severe (≥ Grade 3) hypersensitivity to any enfortumab vedotin excipient contained in the drug formulation of enfortumab vedotin
• Known genetic disorders associated with radiosensitivity (eg, ataxia telangiectasia, Nijmegen breakage syndrome, Fanconi syndrome)
• Active keratitis or corneal ulcerations
• History of autoimmune disease that has required systemic treatment in the past 2 years
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• Prior allogeneic stem cell or solid organ transplant
• Received a live attenuated vaccine within 30 days prior to randomization

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Condition: Urinary Bladder Cancer, Upper Tract Urothelial Cancer, Urothelial Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06822010

Sponsor: Rutgers, The State University of New Jersey

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum 99 Years
• Gender: All

Inclusion Criteria:

• Subjects must meet all of the following applicable inclusion criteria to participate in the study: 1. Patient has signed Informed Consent Form and is willing and able to comply with all requirements of the protocol. 2. Patient is at least 18 years of age. 3. Naive or recurrent patients with High Grade Ta +/- CIS, non-invasive UTUC in the upper tract (pyelocalyceal system or ureter).
• Histologic confirmation with biopsy is necessary.
• All patients must undergo ureteroscopy with biopsy.
• Non-Invasive Papillary Carcinoma (HGTa) lesions must be maximally ablated with ≤ 15 mm residual papillary disease in total. 4. Favorable high-grade upper tract urothelial carcinoma (UTUC) as per American Urological Association (AUA) risk stratification below (except that multifocality, obstruction, ureteral involvement, bladder involvement will be allowed). 1. If the bladder is involved with NMIBC it should be treated prior to or during Gem/Jel treatments. 5. Patients with ECOG (Eastern Cooperative Oncology Group) performance status <3 (with Karnofsky >40). 6. Patients with life expectancy greater than 24 months at time of screening. 7. Patient has no active urinary tract infection (UTI) as confirmed by urine culture or urinalysis*. 8. Female Patients of childbearing potential**, must have a negative serum pregnancy test at screening and must agree to use two acceptable & effective methods of contraception***, until 6 months post treatment 9. All sexually active male patients must agree to use a condom during intercourse, for at least 48 hours post each instillation. 10. Male patients who have a partner that is a female of childbearing potential must agree to use two acceptable & effective methods of contraception until 6 months post treatment. 11. Patients must not have any other medical condition(s) that make(s) their participation in the study unadvisable in the opinion of the investigator.

Exclusion Criteria:

• Invasive upper tract urothelial carcinoma (suspected cT2-4 on imaging) or lymphadenopathy (cN1-3) Bilateral disease Patient is actively being treated or intends to be treated with systemic chemotherapy during the duration of the trial. 4. Any other malignancy diagnosed within 2 years of trial entry with the exception of: a. Basal or squamous cell skin cancers, or b. Noninvasive cancer of the cervix, or c. Any other cancer deemed to be of low-risk for progression or patient morbidity during trial period (basal or squamous cell skin cancers, noninvasive cancer of the cervix, prostate cancer under active surveillance, renal cancer under active surveillance). 4. Administration not feasible via nephrostomy tube. 5. Inability to deliver the investigational drug to the pyelocalyceal system. 6. Patient has any other medical or mental condition(s) that make(s) his/her participation in the trial unadvisable in the opinion of the treating urologist. 7. Patient has contraindication to mitomycin C (MMC )treatment, or known sensitivity to MMC. 8. Patient has an intractable bleeding disorder (e.g., coagulation factors deficiencies, Von Willebrand Disease). 9. Patient is currently receiving any other investigational agents or has participated in a research protocol involving administration of an investigational product within the past 30 days prior to Visit 1. 10. Pregnant (positive serum pregnancy test), planning to become pregnant during the trial period, breast-feeding, or of childbearing potential and not practicing reliable contraception***. * In case of a symptomatic UTI the patient will be treated with a full course of antibiotics, and the instillation will be postponed until resolution. In the case of asymptomatic bacteriuria, the use of prophylactic antibiotics and postponement of the treatment is left to the discretion of the PI. ** Women of non-childbearing potential: 1. At least 12 months since the last menses, or 2. Without uterus and/or both ovaries, or 3. Has been surgically sterile for at least 6 months prior to trial drug administration.
• Acceptable methods of birth control which are considered to have a low failure rate (i.e., less than 1% per year) when used consistently and correctly, such as implants, injectable, combined (estrogen/progesterone) oral contraceptives, intrauterine devices (IUDs-only hormonal), condoms with spermicide, sexual abstinence or vasectomized partner.

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Condition: Non-Muscle Invasive Bladder Urothelial Carcinoma, Recurrent Non-Muscle Invasive Bladder Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05521698

Sponsor: University of Wisconsin, Madison

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

• Biologic male adults (>= 18 years old)
• Note: Because no dosing or adverse event (AE) data are currently available on the use of bicalutamide in participants < 18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable
• Have suspected non-muscle invasive bladder carcinoma (NMIBC) on clinic-based cystoscopy or imaging as viewed by an American Urological Association (AUA) board-certified urologist
• Have had cross sectional imaging of the abdomen and pelvis (computed tomography [CT] or magnetic resonance imaging [MRI] with or without contrast) within 6 months prior to enrollment with no signs of upper tract urothelial cancer (UC), invasive, nor metastatic disease
• Note: If adenopathy or upper tract abnormalities are identified, a negative biopsy and or ureteroscopy is required prior to enrollment
• Newly suspected, diagnosed, or occasionally recurrent bladder cancer (BC)
• Note: Occasional recurrence is defined as =< 2 prior NMIBC episodes in the 18 months preceding cystoscopy where the index tumor was identified
• Participants with single and multiple tumor lesions
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1
• Total bilirubin =< 1.5 x institutional upper limit of normal (note: in participants with Gilbert's syndrome, if total bilirubin is > 1.5 x upper limit of normal, measure direct and indirect bilirubin and if direct bilirubin is =< 1.5 x upper limit of normal, participants may be eligible)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2 × institutional upper limit of normal
• Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2 × institutional upper limit of normal
• Urine Culture < 50,000 colonies/cc of 1 or more organisms (if found and treated and a confirmed negative culture obtained off antibiotics before study drug is started, they will be eligible)
• Serum Testosterone >= 250 ng/dL
• Thyroid stimulating hormone (TSH) within institutional normal
• White blood cell count (WBC) >= 0.5 × institutional lower limit of normal
• The effects of bicalutamide on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, men who are having sex must wear a condom when engaging in any activity that allows for passage of ejaculate to another person throughout the course of the study and 130 days after receiving last dose of study intervention. Male participants should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak. Additionally, men must agree to not donate sperm for the purpose of reproduction during the study and for a minimum of 130 days after receiving the last dose of study intervention
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Participants who have had a previous exposure to sex hormone (e.g., exogenous androgens) or anti-androgenic therapies (e.g., luteinizing hormone-releasing hormone [LHRH] agonists, LHRH antagonists, 5 alpha reductase-inhibitors, abiraterone or other anti-androgens) within 6 months of accrual
• Participants taking Coumarin derivative anticoagulation (e.g., warfarin). Other anticoagulation medications are allowed.
• Participants receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to bicalutamide.
• History of prior or concurrent muscle invading UC, or concurrent prostatic urethral, urethral, or upper tract UC or non-urothelial bladder cancer
• History of radiation therapy to the pelvis, prostate or prostatic bed, or rectum
• Any condition (uncontrolled intercurrent illness, psychiatric illness, or social situation) for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
• Participants with severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, uncontrolled hypertension, recent arterial or venous thromboembolic events (e.g. pulmonary embolism, cerebrovascular accident including transient ischemic attacks) for which anticoagulation therapy is ongoing, or clinically significant ventricular arrhythmias.
• In the opinion of the investigator, participant has underlying uncontrolled hypertension, high cholesterol, or diabetes.
• Allergy or hypersensitivity to bicalutamide, or excipients, unable or unwilling to take ADT.
• Plans to father a child while enrolled in this study or within 130 days after the last dose of study intervention.

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Condition: Bladder Cancer

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT06986304

Sponsor: Duke University

Phase:

Eligibility:

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

Inclusion Criteria:

• Adults > 18 years
• Histological evidence of urothelial cancer of the bladder for which radical cystectomy is recommended as per the treating physician (e.g., MIBC or high-risk NMIBC, such as high-grade T1 BCG refractory and worrisome histological variants)

Exclusion Criteria:

• Known or suspected hypersensitivity to sulfur hexafluoride lipid microsphere or its components, such as polyethylene glycol (PEG).
• Pregnancy or breastfeeding
• Decline to participate in the study
• Participants who had serious allergic reactions to COVID-19 vaccination.
• Participants with unstable conditions such as hospital in-patients, ICU patients, or high-risk cardiac diseases.

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Condition: Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05879653

Sponsor: Kyoto University Hospital

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

• Participants are eligible to be included in the study only if all of the following criteria apply: 1. Male/female participants who are at least 18 years of age on the day of signing informed consent and who have a first confirmed diagnosis of MIBC with predominant urothelial histology obtained via a diagnostic or maximal TURBT within 90 days prior to enrollment. Note: Participants with mixed histology are eligible provided the urothelial component is ≥50%. 2. Has clinically non-metastatic bladder cancer (N0M0) determined by imaging (CT of the chest and CTU/MRU of abdomen and pelvis), assessed by the site. 3. Male participants: A male participant must agree to use a contraception and not to donate sperm during the administration of MK-3475 and ASG-22CE and for at least 90 days after the last dose of MK-3475 and for 6 months after ASG-22CE. 4. Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: 1. Not a woman of childbearing potential (WOCBP) OR 2. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of MK3475 and for 6 months after ASG-22CE and RT. 5. The participant provides written informed consent for the trial. 6. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention. 7. Demonstrates adequate organ function. All screening laboratory tests should be performed within 10 days prior to the first dose of study intervention.

Exclusion Criteria:

1. Participants are excluded from the study if any of the following criteria apply: Medical Conditions
2. Has the presence of diffuse CIS (multiple foci [4 or greater] of CIS) throughout the bladder.
3. Has the presence of UC at any site outside of the urinary bladder in the previous 2 years except for Ta/T1/CIS of the upper tract if the patient has undergone a complete nephroureterectomy.
4. Has the presence of any small cell or neuroendocrine component in the tumor tissue sample.
5. Has a known additional malignancy that is progressing or has required active therapy within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer or other carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) who have undergone potentially curative therapy are not excluded. Participants with low-risk prostate cancer (T1-T2a, Gleason score ≤6, and PSA <10 ng/mL) either treated with definitive intent any time before screening or untreated in active surveillance are not excluded.
6. Has limited bladder function with frequency of small amounts of urine (< 30 mL), urinary incontinence, or requires self-catheterization or a permanent indwelling catheter.
7. Has a history of radiation therapy to the pelvic region for any reason. Prior/Concomitant Therapy
8. Has received prior pelvic/local radiation therapy or any antineoplastic treatment for MIBC. Note: Prior treatment for NMIBC with intravesical instillation therapy such as BCG or intravesical chemotherapy is permitted, but must be completed ≥28 days before the first dose of the trial drug. Prior systemic treatment received for treatment of NMIBC is not permitted.
9. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
10. Has received prior therapy with an ASG-22CE or other MMAE-containing ADCs.
11. Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed. Note: please refer to Section 5.5 for information on COVID-19 vaccines Prior/Concurrent Clinical Study Experience
12. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 3 months before the first dose of study intervention. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent. Diagnostic Assessments
13. A WOCBP who has a positive urine pregnancy test within 72 hours prior to the first dose of study intervention (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
14. Has uncontrolled diabetes. Uncontrol diabetes is defined as hemoglobin A1c (HbA1c) ≥8% or HbA1c 7% to <8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
15. Has ongoing sensory or motor neuropathy Grade 2 or higher.
16. Has active keratitis or corneal ulceration. Subjects with superficial punctate keratitis are allowed if the disorder is being adequately treated in the opinion of the investigator.
17. Has received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids. Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease, with a 1-week washout, is permitted.
18. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial drug.
19. Has severe hypersensitivity (≥Grade 3) to MK-3475, ASG-22CE and/or any of their excipients.
20. Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid).
21. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
22. Has an active infection requiring systemic therapy.
23. Has a known history of Human Immunodeficiency Virus (HIV) infection. The test should be performed within 28 days prior to the first dose of the trial drug.
24. Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection. The test should be performed within 28 days prior to the first dose of the trial drug.
25. Has not adequately recovered from major surgery or has ongoing surgical complications.
26. 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.
27. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
28. Pregnant or lactating, or female patients or male patients who wish to become pregnant from the time of screening to 120 days after the last dose of MK-3475 and 6 months after radiotherapy and the last dose of ASG-22CE, or their partners.
29. Has had an allogenic tissue/solid organ transplant.
30. Has a documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with NYHA Class IV within 6 months prior to the first dose of the trial drug.
31. Or, if participation in this clinical trial is considered inappropriate according to the judgment of the investigator.

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Condition: Advanced Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06434350

Sponsor: M.D. Anderson Cancer Center

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

1. Pathologically confirmed diagnosis of urothelial carcinoma of the bladder including patients with T4N0 and T1-4N2-3 disease. Participants with mixed urothelial carcinoma of bladder will also be included.
2. Be ≥ 18 years of age on the day of signing informed consent.
3. ECOG performance status 0-
4. NOTE: If participants is unable to walk due to paralysis, but is mobile in a wheelchair, participants is ambulatory for the purpose of assessing their performance status.
5. The participant has the following baseline laboratory data:
6. Hemoglobin ≥ 9 g/dL
7. Platelet count ≥ 100 x 109 g/dL
8. Creatinine clearance (CrCl) ≥ 30 mL/min as estimated per institutional standards (glomerular filtration rate [GFR] can also be used instead of CrCl)
9. Absolute neutrophil count (ANC) ≥ 1500/mm3
10. Male participants must consistently use highly effective methods of birth control starting at screening and continue throughout study period and for at least 6 months after radiation completion
11. Female participants must consistently use highly effective methods of birth control starting at screening and continue throughout the study period and for at least 6 months after radiation completion As the CORe system in MDACC is set up as a one-step enrollment process, the above inclusion criteria will be assessed prior to CORe enrollment. Following CORe enrollment, the below inclusion criteria will be assessed.
12. Candidate for definitive local therapy to active disease per the discretion of the treating physicians. Exclusion Criteria:
13. Has a diagnosis of active scleroderma, lupus, ulcerative colitis, or other rheumatologic disease which in the opinion of the treating radiation oncologist precludes safe radiation therapy.
14. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial as determined by the treating physician and/or member of the study team.
15. Distant metastatic disease beyond lymph node metastases, which by the discretion of the treating physician cannot be treated definitively in a radiation field
16. Has history of prior pelvic radiation therapy
17. Has ongoing clinically significant toxicity (Grade 2 or higher with exception of alopecia) associated with prior systemic therapy
18. History of uncontrolled diabetes mellitus within 3 months of enrollment. Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) ≥ 8% or HbA1c between 7 and < 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
19. Has estimated life expectancy of less than 12 weeks
20. Has preexisting sensory or motor neuropathy Grade ≥ 2
21. Participants receiving ongoing systemic intravenous antimicrobial treatment for active infection at time of randomization
22. Participants have a known history of hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. No testing for hepatitis B and hepatitis C is required unless mandated by local health authority.
23. Has a known history of human immunodeficiency virus (HIV) infection. Testing is not required unless mandated by the local health authority.
24. Has conditions requiring high doses of steroids (>10 mg/day of prednisone or equivalent) or other immunosuppressive medications are excluded. Inhaled or topical steroids are permitted in the absence of active autoimmune disease. Physiologic replacement doses of corticosteroids are permitted for participants with adrenal insufficiency.
25. Has a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
26. Has received a prior allogeneic stem cell or solid organ transplant.
27. Has active tuberculosis As the CORe system in MDACC is set up as a one-step enrollment process, the above inclusion criteria will be assessed prior to CORe enrollment. Following CORe enrollment, the below

Exclusion Criteria:

• 1. Has a diagnosis of active scleroderma, lupus, ulcerative colitis, or other rheumatologic disease which in the opinion of the treating radiation oncologist precludes safe radiation therapy. 2. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial as determined by the treating physician and/or member of the study team. 3. Distant metastatic disease beyond lymph node metastases, which by the discretion of the treating physician cannot be treated definitively in a radiation field 4. Has history of prior pelvic radiation therapy 5. Has ongoing clinically significant toxicity (Grade 2 or higher with exception of alopecia) associated with prior systemic therapy 6. History of uncontrolled diabetes mellitus within 3 months of enrollment. Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) ≥ 8% or HbA1c between 7 and < 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained. 7. Has estimated life expectancy of less than 12 weeks 8. Has preexisting sensory or motor neuropathy Grade ≥ 2 9. Participants receiving ongoing systemic intravenous antimicrobial treatment for active infection at time of randomization 10. Participants have a known history of hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. No testing for hepatitis B and hepatitis C is required unless mandated by local health authority. 11. Has a known history of human immunodeficiency virus (HIV) infection. Testing is not required unless mandated by the local health authority. 12. Has conditions requiring high doses of steroids (>10 mg/day of prednisone or equivalent) or other immunosuppressive medications are excluded. Inhaled or topical steroids are permitted in the absence of active autoimmune disease. Physiologic replacement doses of corticosteroids are permitted for participants with adrenal insufficiency. 13. Has a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. 14. Has received a prior allogeneic stem cell or solid organ transplant. 15. Has active tuberculosis As the CORe system in MDACC is set up as a one-step enrollment process, the above inclusion criteria will be assessed prior to CORe enrollment. Following CORe enrollment, the below exclusion criteria will be assessed. 1. Is pregnant or expecting to conceive within the projected duration of the trial at the screening visit.
• Female participants of childbearing potential should have a negative urine or serum pregnancy within 6 weeks prior to study registration up to the first fraction of radiation.
• Note: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

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Condition: Bladder Cancer, Muscle-Invasive Bladder Carcinoma, Stage II Bladder Cancer AJCC v8, Stage IIIA Bladder Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06470282

Sponsor: University of California, San Francisco

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

• Biopsy-confirmed muscle-invasive bladder cancer (cT2,T3,T4a). (Note: Tissue samples are required.) (Participants with cT3/T4a staged disease will be capped at 25% of patients treated at RP2D).
• Urothelial histology present. Mixed histologies other than small cell/neuroendocrine are allowed as long as some urothelial histology is present. Neuroendocrine histology of any component and pure variant (non-urothelial) histology tumors will be excluded. (Patients with < 50% urothelial histology will be capped at 25% of patients treated at RP2D).
• Must be judged by the investigator to be ineligible for radical cystectomy or electing not to undergo radical cystectomy.
• Must be eligible for and agree to receive bladder irradiation as determined by the treating investigator.
• Must have a TURBT within 8 weeks of combination treatment start with viable tumor content. If no viable tumor content is present on TURBT, the patient will be replaced in the study.
• Patients who have autoimmune disease will be evaluated on a case-by-case basis and can only enroll so long as participants are not on active immunosuppression with a corticoid steroid allowance exceeding 10mg of prednisone or equivalent per day.
• Age >= 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status <= 1.
• Absolute neutrophil count ≥ 1,500/microliter (mcL).
• Platelets >= 100,000/mcL.
• Hemoglobin >= 9.0 g/dL or ≥ 5.6 mmol/L. * Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks
• Total bilirubin <= 1.5 × upper limit of normal, unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits.
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase (SGOT)) <= 2.5 X institutional upper limit of normal.
• Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase (SGPT)) <= 2.5 X institutional upper limit of normal.
• Creatinine clearance glomerular filtration rate (GFR) >= 30 mL/min/1.73 m^2, calculated by Cockcroft-Gault or measured using 24-hour creatinine clearance.
• International normalized ratio (INR) OR prothrombin time (PT) <= 1.5 × upper limit of normal (ULN). * If participant is receiving anticoagulant therapy, as long as PT or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants, participant is eligible.
• Activated partial thromboplastin time (aPTT) <= 1.5 × ULN. * If participant is receiving anticoagulant therapy, as long as PT or aPTT is within therapeutic range of intended use of anticoagulants, participant is eligible.
• Ability to understand and the willingness to sign a written informed consent document.
• Human immunodeficiency virus (HIV)-infected individuals on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• Participants who are hepatitis B virus surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) anti-viral therapy for at least 4-weeks, and have undetectable HBV viral load prior to randomization. Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention. * Note: Hepatitis B screening tests are not required unless patients have a known history of HBV infection.
• Participants with a history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening. * Note: Participants must have completed curative anti-viral therapy at least 4 weeks prior to cycle 1 day 1.
• Women of child-bearing potential and men with sexual partners of childbearing potential must agree to use adequate contraception for the duration of study participation. Enfortumab vedotin (EV) may cause fetal harm. Women of child-bearing potential must use contraception during treatment with EV and for 120 days after the last dose. Men with female partners who are women of child-bearing potential must use contraception during treatment with EV and for 120 days after the last dose. 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. Acceptable methods include barrier method, hormonal method, as well as intrauterine devices
• Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 8 weeks after last administration of study treatment.

Exclusion Criteria:

• Presence of distant metastases on imaging (M1 disease).
• Presence of ≥ N2 disease on imaging (N1 disease allowed, but participants with N1 disease will be capped at 25% of patients treated at RP2D).
• Presence of small cell / neuroendocrine histology in tumor sample (any content).
• Absence of urothelial histology in TURBT tumor sample (pure variant histology).
• Presence of untreated upper tract urothelial cancer.
• Presence of severe hydronephrosis precluding therapy in the judgement of the treating physician.
• Presence of extensive carcinoma in situ (CIS) is exclusionary; moderate CIS that could still benefit from radiation treatment in the judgement of treating physician is allowed.
• Baseline neuropathy grade 2 (G2) or greater.
• Baseline uncontrolled diabetes mellitus.Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) ≥ 8% or HbA1c 7 to < 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained. * Note: Patients with prior diagnosis but with disease under control are eligible
• Prior treatment with systemic immunotherapy or chemotherapy for urothelial cancer. (with the exception of prior systematic therapy treatment >12 months prior). Note: Prior bacillus calmette-guerin (BCG) and intravesical treatments are allowed
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to cycle 1 day 1.
• Has received prior radiotherapy within 2 weeks of cycle 1 day 1 or had radiation-related toxicities requiring corticosteroids.
• Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. * Note: Administration of killed vaccines is allowed. Any licensed coronavirus 2019 (COVID-19) vaccine (including for emergency use) is allowed in the study as long as they are messenger ribonucleic acid (mRNA) vaccines, replication-incompetent adenoviral vaccines, or inactivated vaccines.
• Major surgery within 2 weeks prior to first dose of EV. * Note: Cataract surgery, standard tissue biopsies, and standard of care cardiac devices, such as a pacemaker or stent placed on an elective basis, are allowable procedures.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. * Note: Inhaled or topical steroids are permitted.
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
• Has known active CNS metastases and/or carcinomatous meningitis.
• History of another significant life-limiting malignancy requiring systematic treatment within 2 years prior to the first dose of study drugs, or any evidence of residual disease from a previously diagnosed malignancy. * Note: Patients with nonmelanoma skin cancer, curatively treated localized prostate cancer, curatively treated upper tract urothelial cancer, or carcinoma in situ of any type (if complete resection was performed) are allowed.
• Hypersensitivity to pembrolizumab or enfortumab vedotin, or any of their excipients.
• Prior allogeneic stem cell or solid organ transplant.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.
• 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.
• History of Hepatitis B with detectable HBV viral load (participants who are HBsAg positive are eligible if they have received HBV anti-viral therapy for at least 4 weeks, and/or have undetectable HBV viral load prior to randomization) or known active hepatitis C virus (defined as detectable HCV RNA .[qualitative]) infection. * Note: Testing for Hepatitis B or C is not required unless clinically indicated or if there is a known history of hepatitis infection. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Pregnant and breast feeding participants are excluded from this study because targeted chemotherapy and radiation have 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 EV+pembrolizumab, breastfeeding should be discontinued if the mother is treated with these investigational products.

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Condition: Bladder Cancer

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT07545694

Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Phase:

Eligibility:

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

Inclusion Criteria:

• Age ≥ 18 years.
• Patients with bladder carcinoma at any stage of disease, undergoing upfront surgery or neoadjuvant therapy for more than 6 weeks, scheduled for surgery with curative/demolitive intent.
• Signed written informed consent to participate in the study.

Exclusion Criteria:

• Age < 18 years.
• Procedures performed on an urgent/emergency basis.
• Patients treated with corticosteroid therapy for immunorheumatic diseases.
• Patients treated with radio-chemotherapy and undergoing surgery less than 6 weeks prior.
• Refusal to sign written informed consent to participate in the study.

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Condition: Bladder Cancer, Non-Muscle Invasive Bladder Cancer (NMIBC), Urothelial Carcinoma, Carcinoma in Situ (CIS), High-Grade Papillary Bladder Tumors, BCG-Unresponsive Bladder Cancer, Ta Stage Bladder Cancer, T1 Stage Bladder Cancer, BCG-Refractory Bladder Cancer, High-Risk NMIBC, Micropapillary Variant Urothelial Carcinoma (Favorable Subtype)

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT07322263

Sponsor: Michael A. O'Donnell

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum 99 Years
• Gender: All

Inclusion Criteria:

• Histologically confirmed diagnosis of urothelial carcinoma of the bladder without synchronous or metachronous upper tract involvement or prostatic urethral involvement. Subjects with negative upper tract imaging within 6 months of the study start and visually normal prostates are potentially eligible. Those with a history of suspicious upper tract cytology or suspicious prostatic urethra visually will require additional upper tract washes and/or biopsies to rule out concurrent extravesical disease. Eligible bladder cancer presentations include:
• Carcinoma in situ (CIS), with or without non-muscle-invasive stage Ta or T1 tumors of any grade.
• High-Grade Papillary tumors (stages Ta and/or T1) without CIS.
• All visible bladder tumors must be completely resected within 8 weeks prior to initiating intravesical Gem/Doce therapy.
• If more than 8 weeks have passed since diagnosis or resection of index bladder CIS ± non-invasive tumor (pTa or T1 tumors), an office cystoscopy must be performed within 8 weeks of Gem/Doce initiation to confirm no visible tumor regrowth. BCG-Unresponsive Disease as defined by any of the following FDA-accepted criteria:
• Occurrence of high-grade, stage T1 cancer after at least 5/6 weekly BCG induction treatments.
• Occurrence of CIS within 12 months, or high-grade papillary disease, stage Ta/T1, within 6 months after an "adequate" course of BCG therapy. An "adequate" course of BCG includes at least 5/6 weekly BCG induction treatments and at least 2/3 weekly BCG maintenance or 2/6 weekly BCG re-induction treatments.
• N.B: Physician may have some flexibility (+/- 1 month) in the use of 6 and 12 months to define BCG-unresponsive NMIBC.
• N.B: Once a patient has been correctly defined as having BCG-unresponsive disease, they will be considered to always be BCG-unresponsive for the purpose of this study. In other words, there is no restriction as to when the BCG-unresponsive term was assigned.
• The occurrence of low-grade (LG) Ta disease will not be considered a HG relapse event given its prognosis is much more favorable that HG disease. However, all LG tumor must be completely resected before continuing with Gemcitabine/Docetaxel therapy.
• Subjects must be eligible for radical cystectomy and decline this standard of care treatment or not be a surgical candidate for radical cystectomy (as appropriate) based on other comorbidities.
• All grossly visible disease in the bladder must be fully resected with pathologic stage and grade assessed at the local study institution. Local pathologists are strongly encouraged to use the current LG and HG AJCC criteria. NB: For institutions that still use the 3-tiered grading system, Ta Gr1 and Gr 2 will be considered LG while any Ta Gr3 or T1 Gr2 or Gr3 will be considered HG.
• Patients enrolled in other clinical trials must have received their last treatment at least 8 weeks prior to enrollment if the treatment was an intravesical agent. If the treatment included a systemic immune-modulating agent (e.g. anti-PD(L)-1 or anti CTLA4) then at least two dosing intervals must have elapsed untreated before the patient is eligible.
• Age > 18 and must be able to read, understand and sign the local informed consent.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance Status of 2 or less, including patients who are not surgical candidates due to comorbid conditions.
• Women of childbearing potential must have a negative pregnancy test at screening.
• All patients of childbearing potential must be willing to consent to using effective contraception, i.e., IUD, Birth control pills, Depo-Provera, and/or condoms while on treatment and for 3 months after their last Gemcitabine/Docetaxel treatment.
• No intravesical or upper tract topical therapy within 8 weeks of study entry.
• Must be willing and able to comply with all protocol requirements.
• Should have a Complete Blood Count (CBC) with differential before the index tumor resection or biopsy (within 30 days) and/or within 14 days before starting Gemcitabine/Docetaxel therapy.
• Must be willing and able to give informed consent and any authorizations required by the local Institutional Review Board (IRB) for participation in this study.

Exclusion Criteria:

• History or concurrent Stage T2 or greater urothelial cancer.
• History or concurrent upper tract or prostatic urethral cancer (no suspicious or positive upper tract cytology and negative upper tract imaging within 6 months of study entry; visually normal or absent prostatic urethra by cystoscopy).
• History or concurrent variant bladder cancer histology including squamous cell carcinoma, adenocarcinoma, small cell carcinoma, plasmacytoid carcinoma, nested urothelial carcinoma, sarcomatoid carcinoma, squamous, glandular, metastatic carcinoma and others. Select urothelial carcinoma with favorable micropapillary differentiation is permitted (see above).
• Active other malignancies excluding indolent or well-controlled prostate cancer, basal or squamous cell skin cancers or non-invasive cancer of the cervix are permitted so long as they are not expected to impact 3-year survival outcomes.
• History of severe hypersensitivity reaction (>= grade 3) to Gemcitabine and/or Docetaxel.
• History of severe hypersensitivity reaction (>= grade 3) to Polysorbate 80 containing drugs (Docetaxel is formulated with Polysorbate 80)
• Concurrent treatment with any intravesical or systemic chemotherapeutic agent (8-week washout required).
• Treatment with a checkpoint inhibitor within 2 treatment cycles of enrollment.
• Major surgery within 3 months of enrollment.
• Inadequate organ and bone marrow function as evidenced by: 1. Hemoglobin ≤8.0 g/dL. 2. Absolute neutrophil count ≤1.5 x 109/L. 3. Platelet count ≤80 x 109/L. 4. AST/SGOT and/or ALT/SGPT ≥3.0 x ULN. 5. Total bilirubin >1.5 x ULN excepting known benign Gilbert's Disease. 6. Serum creatinine >2.0 x ULN. i. If creatinine 1.5
• 2.0 x ULN, creatinine clearance will be calculated according to CKD-EPI formula and patients with creatinine clearance <30 mL/min should be excluded.
• History of radiation to the pelvis.
• History of difficult catheterization that in the opinion of the Investigator will prevent safe and/or reliable administration of the intravesical agents.
• History of interstitial cystitis or current inability to hold ~ 2 ounces of fluid in the bladder for the expected 60-minute retention time (assistive medication and/or techniques (gravity reflux; split dosing) are permitted).
• Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy (3- week documented clearance required).
• Known human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C infection.
• Recent Covid infection within 30 days of enrollment or currently symptomatic of Covid-related illnesses.
• Significant cardiovascular risk (e.g., coronary stenting within 8 weeks, myocardial infarction within 6 months).
• Women who are pregnant or lactating.
• Participation in any other research protocol involving administration of an investigational agent within 6 weeks of study entry (8-week washout required)
• Any other major or unstable medical condition that in the Investigator's opinion, could affect patient performance status, ability to receive the intravesical therapy and/or life expectancy during the five years of intended study participation.

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Condition: Muscle-invasive Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT07475806

Sponsor: Astellas Pharma Global Development, Inc.

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

• Participant has histologically-confirmed MIBC, stage cT2-T4aN0M0 or T1-T4aN1M0. NOTE: urothelial carcinomas (UCs) not originating from the bladder (e.g., upper tract [ureters, renal pelvis], urethra) are not eligible. UCs invading into the prostatic stroma with no histologic muscle invasion is allowed, provided that the extent of disease is confirmed via imaging.
• Participant has predominant UC histology (≥ 50%). NOTE: Participants with mixed histology are eligible provided the urothelial component is ≥ 50% (participants whose tumors contain predominant [≥ 50%] plasmacytoid variant are not eligible). Participants whose tumors contain any neuroendocrine histology are not eligible.
• Participant is deemed eligible for radical cystectomy and pelvic lymph node dissection.
• Participant has accessible archival tumor tissue from the primary tumor, for which source and availability have been confirmed prior to study intervention. If no archival tumor tissue is available, the participant will have a biopsy to obtain tumor tissue prior to study intervention.
• Participant has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Have a transurethral resection of a bladder tumor within 60 days (+14 days) prior to screening (from the date of informed consent form signature).

Exclusion Criteria:

• Participant has preexisting sensory or motor neuropathy Grade ≥ 2.
• Participant has ≥ N2 disease or metastatic disease (M1) as identified by imaging
• Participant has a history of uncontrolled diabetes mellitus within 3 months prior to screening. Uncontrolled diabetes (within 3 months before first dose) is defined as hemoglobin A1c (HbA1c) ≥ 8% or HbA1c between 7% and < 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained. The lowest HbA1c during the screening period will be used to determine eligibility.
• Participant has a second malignancy diagnosed within 3 years before first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy. Participant with non-melanoma skin cancer, localized prostate cancer treated with curative intent with no evidence of progression, low-risk or very low-risk (per standard guidelines) localized prostate cancer under active surveillance/watchful waiting without intent to treat, or carcinoma in situ of any type (if complete resection was performed) are allowed.
• Participant has known active keratitis or corneal ulcerations. Participant with superficial punctate keratitis is allowed if the disorder is being adequately treated.
• Participant has a history of (non-infectious) pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD.
• Participant has a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
• Participant has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention. Inhaled or topical steroids are permitted in the absence of active autoimmune disease. Physiologic replacement doses of corticosteroids are permitted for participants with adrenal insufficiency.
• Participant has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• Replacement therapy (e.g., thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
• Brief (< 7 days) use of systemic corticosteroids is allowed when use is considered standard of care.
• Participant with vitiligo, psoriasis, type 1 diabetes mellitus, hypothyroidism, or resolved childhood asthma/atopy will not be excluded.
• Participant requiring intermittent use of bronchodilators, inhaled steroids, or local steroid injections will not be excluded.
• Participant with hypothyroidism that is stable with hormone replacement therapy or Sjögren's syndrome will not be excluded.
• Participant has received prior therapy with an anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), or anti-programmed death-ligand 2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).
• Participant has received prior systemic anti-cancer therapy for MIBC/non-muscle invasive bladder cancer (NMIBC), or received prior systemic anti-cancer therapy including investigational agents (including enfortumab vedotin or other monomethyl auristatin E-based antibody-drug conjugates) within 3 years prior to screening. NOTE: Prior treatment for NMIBC with intravesical instillation therapy such as Bacillus Calmette-Guérin or intravesical chemotherapy is permitted. Prior systemic treatment (including, but not limited to, anti-PD-1/PD-L1 treatment with pembrolizumab, etc.) received for NMIBC is not permitted.
• Participant has received a partial cystectomy of the bladder to remove any NMIBC or MIBC.
• Participant has received any prior radiotherapy to the bladder.

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Condition: Urothelial Cancer, Advanced/Metastatic Urothelial Cancer, Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT07421700

Sponsor: Pfizer

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

• Age ≥18 years at the time of screening.
• Histologically confirmed locally advanced or metastatic urothelial carcinoma (LA/mUC).
• Measurable disease per RECIST v1.1 criteria.
• ECOG performance status of 0 or 1.
• Adequate organ function, including hematologic, hepatic, and renal parameters.
• Willingness to comply with study procedures and provide informed consent.
• For participants of childbearing potential: agreement to use effective contraception during the study and for a defined period after the last dose.

Exclusion Criteria:

• Participants will be excluded if they meet any of the following:
• History of another malignancy within 3 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy
• Known active CNS lesions, including leptomeningeal metastasis, brainstem, meningeal, or spinal cord metastases or compression
• Active autoimmune diseases requiring systemic treatment within the past 2 years
• Participation in another investigational study within 30 days or 5 half-lives of the investigational product.
• Pregnant or breastfeeding individuals.
• Inability or unwillingness to comply with study requirements.
• Study staff or their immediate family members directly involved in the conduct of the study.

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Condition: Advanced Urothelial Cancer, Metastatic Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT07484022

Sponsor: Generate Biomedicines

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

• Planned to receive standard-of-care treatment with enfortumab vedotin (EV) (starting dose 1.25 mg/kg) in combination with pembrolizumab for locally advanced or metastatic urothelial cancer.
• Age ≥18 years.
• ECOG Performance Status score of 0 or 1 (ECOG 2 excluded in Dose Escalation but allowed in Dose Expansion).
• Weight ≥50 kg at screening.
• Life expectancy ≥3 months, as determined by the investigator.
• Participants must provide written informed consent before any study-related activities are carried out and must be able to understand the nature and purpose of the study, including potential risks and adverse effects.
• Willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.

Exclusion Criteria:

• Previously received enfortumab vedotin (EV) or other MMAE-based antibody-drug conjugates (ADCs).
• Received anti-cancer treatment with chemotherapy, biologics, or investigational agents within 4 weeks before the first dose of EV/pembrolizumab.
• Uncontrolled diabetes.
• Active CNS metastases. Participants with treated CNS metastases are permitted if all of the following criteria are met:
• CNS metastases have been clinically stable for at least 4 weeks prior to screening and baseline scans show no evidence of new or enlarged metastasis.
• The participant is on a stable dose of ≤10 mg/day of prednisone or equivalent for at least 2 weeks (if requiring steroid treatment).
• The participant does not have leptomeningeal disease.
• Ongoing clinically significant toxicity associated with prior treatment (including radiotherapy or surgery) that has not resolved to Grade ≤1 or returned to baseline.
• History of a severe (Grade ≥3) allergic or infusion-related reaction to any monoclonal antibody.
• Another underlying medical condition that, in the opinion of the investigator, would impair the ability of the participant to receive or tolerate the planned treatment and follow-up.
• Known psychiatric or substance abuse disorders that would interfere with cooperating with study requirements

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Condition: Suspicion of Bladder Cancer, NMIBC Surveillance

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT07514143

Sponsor: Nucleix Ltd.

Phase:

Eligibility:

• Age: minimum 22 Years maximum N/A
• Gender: All

Inclusion Criteria:

1. Age 22 or older
2. Willing and able to sign the informed consent form
3. Subject(s) that is planned to undergo ,within 60 days, one of the following procedures: 3.1 TURBT due to suspected or detected bladder tumor, or 3.2 Cystoscopy under general anesthesia due to suspected bladder tumor, or 3.3 Cystoscopy for NMIBC surveillance

Exclusion Criteria:

1. Patients with known or history of muscle invasive bladder cancer (MIBC)
2. Treatment of prostate cancer or RCC in the past 2 years
3. Patients previously enrolled into this study within the prior 60 days

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