Protocol: SWOG – S1937

Please Note:  Below is a partial list of eligibility, please contact GHCI Research Department at (810) 762-8181, (810) 762-8079 or (810) 762-8038 to discuss full eligibility requirements.

Eligibility:

SCHEMA S1937

1. Participant must have predominant histologically and cytologically proven urothelial carcinoma in a metastatic site.
2. Participant must have evidence of metastatic urothelial carcinoma based on CT or MRI within 28 days prior to registration.
3. Participant must have had progression of disease following prior therapy at the discretion of the treating investigator.
4. Participants must not require immediate CNS-specific treatment, in the opinion of the treating investigator if they have active brain metastases (defined as new or progressive brain metastases) or leptomeningeal disease.
5. Participant must have received previous systemic treatment for metastatic urothelial carcinoma with either a platinum-based chemotherapy regimen, systemic PD1/PDL1 immunotherapy, an antibody drug conjugate such as,
   enfortumab vedotin or sacituzumab govitecan (through standard of care or a clinical trial) . There is no limit to the number of prior regimens patient may have received for urothelial carcinoma.
6. If participant is a candidate for a platinum-based chemotherapy, then participant must have previously received a platinum-based chemotherapy.
7. If participant is a candidate for immunotherapy, then participant must have previously received immunotherapy. If participant is not a candidate for immunotherapy, then participant either: (a) must have had prior anti
   PD1/PDL1 antibody therapy; OR (b) must have not been a candidate for anti PD1/PDL1 antibody therapy in the opinion of the treating physician.
8. Participant is eligible if platinum based chemotherapy and/or anti PDL/PDL1 antibody therapy was provided in perioperative setting before or after radical cystectomy and if there is evidence of progression to metastatic disease within 12 months of the last dose of therapy. For instance, a patient treated with ddMVAC in neoadjuvant setting, then radical cystectomy followed by adjuvant pembrolizumab on AMBASSADOR trial will meet the requirement for prior/concurrent therapy if progression of disease occurs within 12 months of discontinuation of pembrolizumab.
9. Participant must have received any planned surgery prior to registration.
10. Participant must not have progressed within 3 months following last dose of gemcitabine.
11. Must be at least 18 years of age.
12. Zubrod Performance Status 0-2.
13. Participants may have a prior or concurrent malignancy provided the natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen per the opinion of the treating
    investigator.
14. Participants must not be planning to take strong or moderate CYP3A or CYP2C8 inhibitors or inducers if randomized to Arm 1 and SOC regimen chosen is Paclitaxel or Docetaxel. Participants receiving strong or moderate CYP3A or
    CYP2C8 inducers must discontinue use at least 2 weeks prior to randomization.

Protocol: Alliance – A031901

Please Note: Below is a partial list of eligibility, please contact GHCI Research Department at (810) 762-8181, (810) 762-8079 or (810) 762-8038 to discuss full eligibility requirements.

Eligibility:

SCHEMA A031901

Pre-Registration: 

1. Histologically or cytologically confirmed urothelial carcinoma (UC) with predominantly transitional-cell features. Locally advanced or metastatic disease prior to starting immune checkpoint blockade.
2. Patients must have received at least one cycle of current active treatment with standard of care (SOC) FDA approved PD-1/L1 immune checkpoint inhibitor (ICI)-containing therapy for locally advance or metastatic UC.
3. No current immunosuppressive medication exceeding 10mg/day of prednisone or its equivalent.
4. No history of another primary malignancy except for malignancy treated with curative intent with no known active disease for ≥ 2 years, and adequately treated nonmelanomatous skin cancer or carcinoma in situ (e.g. cervical CIS) without evidence of disease.

Registration:

1. Patients without progressive disease per RECIST v 1.1 guidelines (i.e., with an ongoing CR, PR or SD) following completion of 12-15 months of ICI treatment.
2. At least 18 years of age.
3. ECOG Performance Status 0-2.

PROTOCOL: Alliance-A031803

Please Note: Below is a partial list  of eligibility, please contact GHCI Research Department at (810) 762-8181, (810) 762-8079 or (810) 762-8038 to discuss full eligibility requirements.

ELIGIBILITY:

SCHEMA A031803

1. High grade Ta, T1 or CIS urothelial carcinoma. Accrual of patients with Ta or T1 disease may be closed to ensure adequate patients enrollment to meet the primary endpoint.
2. Persistent disease after completing therapy with at least induction BCG (≥5 doses) and the first round of maintenance or second induction course (≥2 doses).  Persistent high risk NMIBC (T1, high grade Ta and/or CIS) must be within
   9 months of the last BCG instillation despite having received adequate BCG as defined above.
3. High grade T1 after completing therapy with at least induction BCG (≥5 doses) or after completing therapy with at least induction BCG (≥5 doses) and first round of maintenance or second induction course (≥2 doses).  Persistent high risk NMIBC (T1, high grade Ta and/or CIS) must be within 9 months of the last BCG instillation despite having received adequate BCG as defined above.
4. Mixed variant histology (adenocarcinoma, squamous cell carcinoma) is eligible, but pure variant histology is ineligible.
5. Patients who are disease free at 6 months after starting BCG but have high grade recurrence (T1, Ta, CIS) while on maintenance therapy would be eligible.  The recurrence must be within 6 months of the last BCG dose.
6. Patients must be deemed unfit for radical cystectomy by the treating physician or refuse radical cystectomy.
7. All visible tumor must be completely resected 60 days prior to registration (residual pure CIS is permitted). All patients must have histologically confirmed urothelial cancer of the bladder within 60 days prior to registration. All patients must have had a cystoscopy without papillary tumor and negative urinary cytology within 21 days of registration. (positive cytology is allowed in patients with pure CIS).
8. All patients with T1 tumors must undergo a re-staging transurethral resection of bladder tumor (TURBT) within 60 days of registration.There must be uninvolved muscularis propria present in the re-staging TURBT.
   The initial TURBT prior to re-staging TURBT may be greater than 60 days prior to registration.
9. Patients must have had imaging with CT or MRI abdomen/pelvis within 90 days of registration demonstrating no evidence of metastasis.
10. Patients cannot have had a history of urothelial carcinoma in the ureters or prostatic urethra 24 months prior to registration.
11. Patients must not have 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 (e.g., CTLA-4, OX 40, CD137).
12. Patients must not have received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to treatment.
13. At least 18 years of age.
14. ECOG Performance Status 0-2.
15. Patients must not have received live vaccines within 30 days of study drug administration.

PROTOCOL:  Alliance-A031701

Please Note: Below is a partial list of eligibility, please contact GHCI Research Department at (810) 762-8181, (810) 762-8079 or (810) 762-8038 to discuss full eligibility requirements.

ELIGIBILITY:

SCHEMA A031701

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. A single muscle-invasive bladder tumor measuring ≤5 cm in size as defined by the surgeons at cystoscopic evaluation. When documented, pathologic size at cystoscopy and TURBT will take precedence over radiographic measurements of tumor size.
6. No clinical or radiographic evidence for locally advanced or metastatic disease.
7. No prior anti-PD-1 or anti PD-L1 therapies, or systemic chemotherapy within the past 5 years (prior intravesical induction immunotherapy for non-muscle invasive disease is allowed, defined as BCG x6 doses and maintenance therapy); BCG refractory disease, defined as disease recurrence within 3 months of BCG therapy, is not allowed. Intravesical chemotherapy is allowed.
8. No prior radiation therapy to the bladder or prostate.
9. No major surgery or radiation therapy <4 weeks of registration (TURBT is allowed).
10. At least 18 years of age.
11. ECOG Performance Status 0-1.
12. No prior malignancy except for: adequately treated basal or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years. Patients with localized prostate cancer who are being followed by an active surveillance program are also eligible.