Phase II Trial of Intravesical Gemcitabine and Pembrolizumab in Treatment of Patients with BCG Unresponsive Non-Muscle Invasive Bladder Cancer

PROTOCOL: Alliance-A031803

SCHEMA A031803

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

ELIGIBILITY:

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.