Intravesical GEM/DOCE for HR BCG-Unresponsive NMIBC

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.