Clinical Trial Information

Protocol: Alliance – A031901

SCHEMA A031901

Please Note: Below is a brief description of eligibility, please contact GHCI Research Department to discuss full eligibility requirements.

Eligibility:

1. Histologically or cytologically confirmed urothelial carcinoma with predominantly transitional-cell features.
2. Locally advanced or metastatic disease prior to starting immune checkpoint blockage. TUMOR SITE: Bladder, renal, pelvis, ureter or urethra.
3. Patients must be receiving current active treatment with standard care, FDA approved PD-1/L1 immune checkpoint inhibitor containing therapy for locally advance or metastatic.
4. Radiographic response 12-15 months after starting  immune checkpoint inhibitor containing treatment, defined as any percent decrease in target and/or non-target lesion(s) criteria that is confirmed by repeat assessment(s) no less than 4 weeks after the criteria for response are first met without evidence of progressive disease.
5. No toxicity from immune checkpoint inhibitor therapy that makes continuation of treatment acceptable.
6. 18 years of age.
7. ECOG performance status 0-2.
8. No history of another primary malignancy except for malignancy treated with curative intent with no known active disease for more than 2 years, and adequately treated non-melanomatous skin cancer or carcinoma in situ (e.g. cervical CIS) without evidence of disease.

Clinical Trial Information

PROTOCOL: Alliance-A031803

SCHEMA A031803

Please Note: Below is a brief description of eligibility, please contact GHCI Research Department to discuss full eligibility requirements.

ELIGIBILITY:

1. High grade Ta, T1 or CIS urothelial carcinoma and Recurrent disease after completing therapy with at least induction BCG
   (≥5 doses) and the first round of maintenance or second induction course (≥2 doses).
2. Patients must be deemed unfit for radical cystectomy by the treating physician or refuse radical cystectomy.
3. All visible tumor must be completely resected within 60 days of before registration (residual pure CIS is permitted).
4. All patients must have histologically confirmed urothelial cancer of the bladder within 60 days after starting BCG.
5. All patients must have had a cystoscopy without papillary tumor and negative urinary cytology within 21 days before
   registration. (Positive cytology is allowed in patients with pure CIS).
6. Mixed variant histology (adenocarcinoma, squamous cell carcinoma)
7. Patients with T1 tumors must undergo a re-staging TURBT within 60 days before registration.
8. No evidence of metastasis documented with CT or MRI abd/pelvis within 90 days prior to registration.
9. No history of urothelial carcinoma in the ureters or prostatic urethra within 24 months of registration.
10. No prior or concurrent systemic chemotherapy or immunotherapy. (Prior intravesical chemo and interferon is allowed. Single dose chemotherapy post TURBT is allowed.)
11. No prior bladder radiation.
12. Age ≥ 18 years.
13. ECOG Performance Status: 0-2.
14. No known additional malignancy that has had progression or has required active treatment in the last three years.
15. History of prostate cancer that was treated with definitive intent is allowed.
16. No active autoimmune disease requiring systemic treatment within 24 months prior to registration.

Clinical Trial Information

PROTOCOL: Alliance-A031701

SCHEMA A031701

Please Note: Below is a brief description of eligibility, please contact GHCI Research Department to discuss full eligibility requirements.

ELIGIBILITY:

1. Histologically confirmed muscle-invasive urothelial carcinoma of the bladder. Urothelial carcinoma invading into the prostatic stroma with no histologic muscle invasion is allowed, provided the extent of disease is confirmed via imaging and/or EUA. The diagnostic TURBT sample must have been obtained within 60 days prior to registration.
2. Clinical stage T2-T4aN0/xM0 disease.
3. Medically appropriate candidate for radical cystectomy as assessed by surgeon.
4. No concomitant multifocal carcinoma in situ; a single focus is allowed.
5. One focus of muscle-invasive bladder cancer and/or a tumor <5 cm in size.
6. No clinical or radiographic evidence for locally advanced or metastatic disease.
7. No prior anti-PD-1, anti PD-L1 therapies, or systemic chemotherapy (prior intravesical induction immunotherapy for non-muscle invasive disease is allowed, defined as BCG x6 treatments; BCG refractory disease, defined as disease recurrence within 3 months of BCG therapy, is not allowed).
8. No prior radiation therapy to the bladder.
9. No major surgery or radiation therapy <4 weeks of registration.
10. Age ≥ 18 years.
11. ECOG Performance Status 0-1.

Clinical Trial Information

PROTOCOL: Alliance-A031501

SCHEMA A031501

Please note: Below is a brief description of eligibility, please contact GHCI Research Department to discuss full eligibility requirements.

Eligibility:

Pre-registration:

1. Histologically confirmed muscle-invasive urothelial carcinoma of the bladder or upper tract.
2. Paraffin tissue available for PD-L1 analysis.
3. Patient must fit into one of the following three categories:
   • Patients who received neoadjuvant chemotherapy and pathologic stage at
   surgical resection is ≥ pT2 and/or N+
   OR
   • Patients who are not cisplatin-eligible (according to ≥ 1 of the following
   criteria: ECOG performance status of 2, creatinine clearance < 60 mL/min,
   grade ≥ 2 hearing loss, grade ≥ 2 neuropathy, or New York Heart Association
   Class III heart failure [38]) and pathologic stage at surgical resection is ≥ pT3
   or pN+)
   OR
   • Patients that decline adjuvant cisplatin-based or other systemic chemotherapy
   based on an informed discussion with the physician and pathologic stage at
   surgical resection is ≥ pT3 or pN+ .
4. Radical resection of bladder cancer ≤16 weeks prior to preregistration.
5. No evidence of residual cancer or mets after surgery.
6. No measurable disease on cross-sectional imaging.
7. No active autoimmune disease or history of autoimmune disease that may recur.
8. No postoperative/adjuvant systemic therapy.
9. No prior treatment with any therapy on the PD-1 Or PD-L1 axis.
10. No, treatment with an investigational agent, major surgery,
    radiation therapy or neoadjuvant chemotherapy ≤4 weeks prior to pre-registration.
11. Age ≥18 years.

Registration Eligibility Criteria:

1. Central PD-L1 results available.