Bladder Cancer

Condition: Bladder (Urothelial, Transitional Cell) Cancer, Non-Muscle Invasive Bladder Carcinoma, Non-muscle Invasive Bladder Cancer With Carcinoma in Situ

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT07480356

Sponsor: Protara Therapeutics

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

• Male or female participants 18 years of age or older at the time of signing informed consent
• Participants who have voluntarily given written informed consent after the nature of the study has been explained according to applicable requirements prior to study entry
• Central histologic confirmation of high-grade non-muscle invasive CIS (± Ta/T1) with active disease
• Participants who are BCG naive, or participants who are BCG exposed and have not received intravesical BCG for at least 24 months prior to the most recent CIS diagnosis, or participants who received ≤2 doses of BCG within the 24 months prior to the most recent CIS diagnosis

Exclusion Criteria:

• Penicillin allergy (participants with a questionable history of allergy to penicillin will undergo penicillin blood allergy testing via central laboratory
• Central confirmed variant histology
• Concomitant prostatic or upper tract urothelial involvement per Investigator's assessment
• Nodal and metastatic disease are excluded if they existed at any time (whether present or in the past)
• Any history of ≥ T2 bladder cancer that existed at any point in time in the participant's history For more information on

Eligibility Criteria:

1. , please contact the Sponsor.

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

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT07673016

Sponsor: Convergent Genomics, Inc.

Phase:

Eligibility:

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

Inclusion Criteria:

• GROUP 1: Bladder Cancer and/or Upper Tract UCC
• Male or female ≥ 18 years of age who are scheduled for transurethral resection of bladder tumor (TURBT) and/or biopsy of urinary tract or
• Patients on surveillance who are negative for recurrence or tumor at the time of study enrollment but have had previous urothelial cell carcinoma (UCC) or
• Patients with muscle invasive bladder cancer (MIBC) or non-muscle invasive bladder cancer (NMIBC) scheduled for NAC and/or subsequent radical cystectomy (RC)
• Able to provide consent prior to diagnostic TURBT, nephroureterectomy, or administration of NAC and/or RC
• Able to provide at least 20cc urine. If patient cannot void sufficient volume of urine, urologist can pull urine from the bladder via catheter or cystoscope. Urine should not be collected immediately after resection
• Participation in other bladder cancer studies is allowed. Experimental therapy must be documented in the case report forms GROUP 2: Hematuria Controls
• Male or female ≥ 18 years of age presenting with gross or microscopic hematuria as defined by standard of care
• No evidence of and/or history of bladder cancer, upper tract UCC, kidney cancer and/or prostate cancer at the time of collection
• Able to provide consent
• Able to provide at least 20cc urine
• Participation in other studies is allowed. Experimental therapy must be documented in the case report forms

Exclusion Criteria:

• GROUP 1: Bladder Cancer and/or Upper Tract UCC
• Clinical, symptomatic urinary tract infection at time of initial urine collection
• Unable to provide adequate urine sample GROUP 2: Hematuria Controls
• Evidence and/or History of bladder cancer, upper tract UCC, kidney cancer and/or prostate cancer at the time of collection

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Condition: Bladder (Urothelial, Transitional Cell) Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT07119996

Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

1. The patient voluntarily agrees to participate, is able to provide written informed consent, and is willing and able to comply with the protocol and schedule of assessments.
2. Aged ≥18 years on the date of signing the informed-consent form (ICF).
3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Appendix 1).
4. Residual tumour after TURBT and histologically confirmed urothelial carcinoma of the bladder staged cT2-T4a N0 M0 by AJCC 8th edition imaging; for mixed-histology tumours, the urothelial component must be predominant (≥50 %).
5. An infection occurring from 30 days to 1 day before the first dose of immuno-chemotherapy that, in the judgement of the attending physician, required oral or intravenous bactericidal antibiotics and met any of the following diagnostic criteria:
6. Clinical features (e.g. ≥38.3 °C or sustained ≥38 °C for ≥1 h with chills, local pain, dysuria, etc.) plus laboratory evidence (WBC > 10 × 10⁹/L or < 4 × 10⁹/L, neutrophilia / neutropenia, markedly elevated CRP) consistent with bacterial infection;
7. Abnormal urinalysis suggestive of urinary-tract infection (e.g. WBC > 10/HPF, bacteria seen on high-power field, nitrite positive) with pathogen confirmed by urine culture;
8. Infection confirmed by imaging or other microbiological tests (e.g. blood culture, nasopharyngeal swab, sputum culture). Permitted bactericidal antibiotics (oral or IV) include but are not limited to:
9. β-lactams (penicillins, cephalosporins, carbapenems);
10. Glycopeptides (vancomycin, teicoplanin);
11. Quinolones (levofloxacin, ciprofloxacin);
12. Aminoglycosides (gentamicin, streptomycin).
13. Adequate organ function, documented within ≤14 days before enrolment: a. No growth-factor support ≤14 days before sampling and: i. Absolute neutrophil count ≥1.5 × 10⁹/L; ii. Platelets ≥90 × 10⁹/L; iii. Haemoglobin ≥90 g/L; b. INR or aPTT ≤1.5 × ULN; c. Total bilirubin ≤1.5 × ULN (≤3 × ULN for Gilbert's syndrome or isolated indirect hyper-bilirubinaemia of extra-hepatic origin); d. AST, ALT and alkaline phosphatase ≤2.5 × ULN; e. Pulmonary function adequate to tolerate major abdominal surgery.
14. Considered cisplatin-eligible by the investigator. Patients deemed cisplatin-ineligible must meet ≥1 of: ECOG > 1 or Karnofsky 60-70 %; creatinine clearance < 60 mL/min; NCI-CTCAE v5.0 grade ≥2 hearing loss; NCI-CTCAE v5.0 grade ≥2 peripheral neuropathy; New York Heart Association class III or IV heart failure.
15. Women of child-bearing potential agree to use highly effective contraception during the study and for ≥120 days after the last dose of tislelizumab or chemotherapy (whichever is later) and have a negative urine or serum pregnancy test ≤7 days before enrolment. Non-sterilised men likewise agree to use highly effective contraception for the same period (Appendix 5).

Exclusion Criteria:

1. Patients meeting any of the following are ineligible:
2. Previous therapy directed against PD-1, PD-L1, PD-L2, CTLA-4 or any other antibody or drug targeting T-cell co-stimulation or checkpoint pathways.
3. Systemic anticancer therapy or systemic immunomodulator (e.g. interferon, interleukin-2, TNF) within 28 days before enrolment.
4. Prior radiotherapy to the bladder.
5. Prior antitumour drug therapy, except:
6. ≥12 months since the last dose of systemic chemotherapy before study neoadjuvant therapy;
7. Intravesical chemotherapy or immunotherapy completed ≥1 week before study treatment.
8. Major surgery or significant trauma within 28 days before enrolment (vascular-access placement and TURBT are not major surgery).
9. Live vaccine within 28 days before enrolment (inactivated seasonal influenza vaccine is permitted; intranasal influenza vaccine is live and prohibited).
10. Active autoimmune disease requiring systemic therapy that, in the investigator's opinion, would interfere with study treatment.
11. Long-term high-dose corticosteroids or other immunosuppressants that, in the investigator's opinion, would interfere with study treatment.
12. Clinically significant abnormalities that could affect treatment, including electrolyte disturbance (K, Na, Ca), hypoalbuminaemia, interstitial lung disease, non-infectious pneumonitis, or other uncontrolled systemic diseases (e.g. diabetes, hypertension, cardiovascular disease such as severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, or clinically significant ventricular arrhythmia within 6 months).
13. Untreated chronic HBV infection with HBV-DNA ≥500 IU/mL (2,500 copies/mL) or HBsAg carrier status. Patients with inactive HBsAg carriage or stable active HBV on antiviral therapy with HBV-DNA < 500 IU/mL may enrol. HBV-DNA testing is required only for anti-HBc-positive patients.
14. Active HCV infection. Patients who are anti-HCV-negative, or anti-HCV-positive but HCV-RNA-negative, may enrol. Anti-HCV-positive patients must have HCV-RNA testing.
15. History of immunodeficiency (including HIV positivity or other acquired/congenital immunodeficiencies), or prior allogeneic stem-cell or solid-organ transplantation (Appendix 3).
16. Known hypersensitivity to other monoclonal antibodies.
17. Known hypersensitivity to any study drug or excipient.
18. Unresolved toxicities from prior therapy that have not returned to baseline or stabilised, unless considered by the investigator not to pose a safety risk (e.g. alopecia, neuropathy, certain laboratory abnormalities).
19. Any condition (medical or substance abuse) that could impede study-drug administration, confound interpretation of results, or place the patient at high risk of complications.

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Condition: Non-Muscle-Invasive Bladder Cancer (NMIBC)

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT07646145

Sponsor: Shanxi Province Cancer Hospital

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

• Voluntary participation, signing a written informed consent form;
• The age on the date of signing the informed consent form should be no less than 18 years old, regardless of gender;
• The subjects have completed the standard TURBT procedure before signing the informed consent form, and no obvious residual tumor lesions were found in the surgical field;
• The postoperative pathology clearly diagnosed as non-muscle-invasive bladder cancer, and the main tissue component was more than 50% urothelial carcinoma (transitional cell carcinoma);
• The subjects were classified into the intermediate-risk or high-risk group according to the risk classification for NMIBC;
• Tumor tissue samples for TURBT must be provided, along with the required relevant pathological reports. Fresh surgical tissues or pathological slides can be sent for examination as well;
• The patients were intolerant to BCG or did not accept the BCG infusion treatment plan;
• Before treatment, HER2 detection was conducted on the resection specimens in the laboratory: The IHC results confirmed HER2 expression (defined as: IHC 1+, 2+ or 3+);
• Clinical non-metastatic bladder cancer (N0, M0) was determined by abdominal computed tomography (CT).

Exclusion Criteria:

• History of muscle-invasive bladder cancer or metastatic bladder cancer before treatment;History of muscle-invasive bladder cancer or metastatic bladder cancer before treatment;
• Imaging results within 3 months before treatment indicated lymph node or other site/organ metastasis;
• Imaging results within 3 months before treatment indicated the presence of other urinary system tumors;
• Received other systemic anti-cancer treatments within 3 weeks before treatment, including chemotherapy, biological therapy, immunotherapy, targeted therapy, endocrine therapy, and/or investigational drug therapy;
• Received bladder radiotherapy for urothelial carcinoma before treatment;
• Known to have anaphylaxis or delayed allergic reaction to certain components of vedacitinib or similar drugs;
• Within the 3 days prior to the first infusion, the following conditions had not yet been alleviated to CTCAE grade 1:Uncontrolled acute or chronic infections, such as pneumonia, biliary tract infections;Hepatitis B and Hepatitis C infections; dyspnea;Acute or chronic kidney injury; nephrotic syndrome; bladder perforation; urinary tract obstruction;
• NYHA rating of 3 or 4;
• Symptoms and signs related to cardiovascular diseases: including myocardial infarction, congestive heart failure, arrhythmia, etc.;
• Known cerebrovascular accidents;
• History of autoimmune diseases (such as inflammatory bowel disease, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, hemolytic anemia, rheumatoid arthritis, etc.);
• Known positive HIV serology, Hepatitis C infection and/or Hepatitis B (HepBsAg or core antibody positive and responding after antiviral treatment for Hepatitis B, except for these patients: these patients are allowed to participate in this study; Note: Patients with negative HepBsAg at screening)

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Condition: Muscle-Invasive Bladder Cancer (MIBC)

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT07647289

Sponsor: Peking University Third Hospital

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

• Voluntarily agree to participate in the study and sign the informed consent form (ICF).
• Age ≥ 18 and ≤ 80 years at the time of signing the ICF.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically confirmed muscle-invasive urothelial carcinoma of the bladder, with variant histology components comprising < 50%.
• Radiographically confirmed non-metastatic urothelial carcinoma (M0). Clinical stage must be locally advanced or possess high-risk features, including at least one of the following: clinical stage cT3-T4aNxM0, or definitive high-risk cT2 (e.g., accompanied by tumor-related hydronephrosis, lymphovascular invasion).
• Participants must be evaluated as fit for and scheduled to undergo radical surgery, and clinically fit to tolerate cisplatin-based chemotherapy.
• Able to provide tumor tissue samples (at least 5 unstained slides, or paraffin scrolls/blocks).
• Expected life expectancy of at least 12 weeks.
• Adequate organ function, defined by the following laboratory values (obtained without blood transfusion within 14 days or growth factor support within 7 days prior to testing): Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L; Platelet count (PLT) ≥ 100 × 10^9/L; Hemoglobin (Hb) ≥ 90 g/L; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × Upper Limit of Normal (ULN); Total bilirubin (TBIL) ≤ 1.5 × ULN; International Normalized Ratio (INR) ≤ 1.5 × ULN; Creatinine clearance ≥ 60 mL/min (calculated using the Cockcroft-Gault formula); Left ventricular ejection fraction (LVEF) ≥ 50%; QTcF interval ≤ 480 ms.
• Female participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose of study treatment and must be willing to use highly effective contraception during the study and for 180 days after the last dose.
• Male participants with female partners of childbearing potential must be surgically sterile or willing to use highly effective contraception during the study and for 180 days after the last dose.
• Able to understand and comply with study visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:

• Prior systemic anti-tumor therapy for urothelial carcinoma, including radiotherapy, chemotherapy, targeted therapy, or biological therapy (except for intravesical instillation therapy).
• Prior treatment with PD-1/PD-L1 inhibitors or antibody-drug conjugates (ADCs).
• Active malignancies other than urothelial carcinoma within 3 years prior to the first dose, except for curatively treated malignancies (e.g., basal or squamous cell skin cancer, localized low-risk prostate cancer, papillary thyroid cancer, carcinoma in situ of the cervix, ductal carcinoma in situ of the breast).
• Active autoimmune disease requiring systemic treatment (e.g., use of disease-modifying agents, corticosteroids, or immunosuppressants) within 2 years prior to the first dose; or received high-dose steroids (>10 mg/day prednisone equivalent) or other immunosuppressive medications within 14 days prior to the first dose. (Physiological replacement therapies are permitted).
• Severe thromboembolic events or severe cardiovascular/cerebrovascular diseases within 1 year prior to the first dose, including but not limited to myocardial infarction, unstable angina, pulmonary embolism, cerebral hemorrhage, cerebral infarction, and deep vein thrombosis.
• Major surgical procedure within 28 days prior to the first dose; or cystoscopy/ureteroscopy biopsy or intravesical therapy within 7 days prior to the first dose.
• Peripheral neuropathy ≥ Grade 2.
• Severe dry eye syndrome, active keratitis, corneal ulcers, or conditions assessed by the investigator as increasing the risk of corneal disease and unsuitable for participation.
• Active infections, including: Positive HBsAg with HBV-DNA copy number ≥ 500 IU/mL; Positive HCV antibody with positive HCV-RNA; Positive HIV antibody; Active tuberculosis infection; Other active infections requiring systemic therapy within 7 days prior to the first dose.
• Other severe or uncontrolled diseases, including but not limited to: Severe respiratory diseases (e.g., moderate-to-severe interstitial or obstructive pulmonary disease, severe asthma); New York Heart Association (NYHA) Class III or IV heart failure; HbA1c ≥ 8% (except for participants whose fasting blood glucose is stably controlled at ≤ 10 mmol/L with medication); Poorly controlled hypertension (systolic BP ≥ 160 mmHg and/or diastolic BP ≥ 100 mmHg); Large pleural effusion or ascites requiring symptomatic treatment within 14 days prior to the first dose.
• Receipt of live vaccines within 28 days prior to the first dose or plans to receive live vaccines during the study.
• Prior allogeneic hematopoietic stem cell transplantation or solid organ transplantation.
• Use of strong CYP3A4 inhibitors or inducers within 14 days prior to the first dose.
• Known severe hypersensitivity or intolerance to the study drugs or any of their excipients.
• Substance abuse or psychiatric disorders that may interfere with study compliance.
• Any other condition that, in the opinion of the investigator, makes the participant unsuitable for the study.

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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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