A Phase 2 Study of Nivolumab or Nivolumab/BMS-986205 Alone or Combined with Intravesical BCG in Participants with Bladder Cancer
- Conditions
- Therapeutic area: Diseases [C] - Cancer [C04]BCG-Unresponsive, High-Risk, Non-Muscle Invasive Bladder CancerMedDRA version: 20.0Level: PTClassification code 10005005Term: Bladder cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2017-003581-27-FR
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 480
1) Signed Written Informed Consent
2) Type of Participant and Target Disease Characteristics
a) Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
b) Life expectancy = 6 months
3) Pathologically demonstrated BCG-unresponsive, high-risk NMIBC defined as carcinoma in situ (CIS) with or without papillary component, any T1, or Ta high-grade lesions; diagnosis required within 8 weeks (56 days) prior to starting treatment and must be confirmed by the Pathology Review Committee (PRC).
a) Predominant histologic component (> 50%) must be urothelial (transitional cell) carcinoma
b) Must have undergone each of the following procedures within 8 weeks (56 days) of randomization. If these procedures are performed as part of the participant’s routine care, they do not need to be repeated provided that they were performed within the required time period:
i) Complete excision of all papillary disease (T1/TaHG). For participants with T1 lesions, a re-staging TURBT must be performed within 4 weeks after the initial TURBT to ensure that the pathology specimen contains muscularis propria that is free of invasive tumor per PRC.
ii) Resection or fulguration of all detectable CIS, if feasible. Fluorescence-guided cystoscopy is encouraged but not mandated. It is understood that due to the nature of this disease, complete resection of CIS cannot be assured.
iii) Random sampling of bladder mucosa for detection of occult CIS. The bladder must be mapped by visual inspection and random biopsies taken from the trigone, right and left lateral walls, posterior wall, dome and prostatic urethra (in male participants).
iv) Urine cytology must be obtained by bladder wash. Recognizing the possibility of occult CIS, cytology at screening does not need to be negative for study participation.
v) Computed tomography (CT) scan of the chest and CT or magnetic resonance imaging (MRI) of the abdomen, pelvis, and all other areas of suspected disease to exclude locally advanced or metastatic bladder cancer or synchronous UC in the upper urinary tracts within 90 days prior to randomization.
vi) Participants should either be deemed medically unfit for radical cystectomy, or should have refused radical cystectomy after consultation with their urologist or oncologist.
c) Pelvic examination, preferably under anesthesia, should be performed to exclude locally advanced disease
d) Availability of a suitable formulation and mode of administration of BMS-986205 for the participant’s needs, as detailed in the IB and pharmacy manual at the time of enrollment.
4) Age and Reproductive Status
a) Males and Females, 18 years of age, or age of majority, and older
b) Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study treatment.
c) Women must not be breastfeeding
d) Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception (see Appendix 4) for the duration of treatment with study treatment plus 5 months after the last dose of study treatment (ie, 30 days [duration of ovulatory cycle] plus the time required for nivolumab to undergo approximately 5 halflives).
e) Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception (see Appendix 4) for the duration of treatment with study treatment plus 7 months after the last dose of the
1) Women who are pregnant or breastfeeding
2) Participants with a personal or family (ie, in a first-degree relative) history of cytochrome b5 reductase deficiency (previously called methemoglobin reductase deficiency) or other diseases that put them at risk of methemoglobinemia. All participants will be screened for methemoglobin levels prior to randomization.
3) Participants with a history of glucose-6-phosphate dehydrogenase (G6PD) deficiency or other congenital or autoimmune hemolytic disorders. All participants will be screened for G6PD deficiency prior to randomization.
4) Evidence of locally advanced or metastatic bladder cancer as seen in cross-sectional imaging of the chest, abdomen, and pelvis
5) UC in the upper genitourinary tract (kidneys, renal collecting systems, ureters) within 24 months of enrollment
6) UC and/or CIS in the prostatic urethra within 12 months of enrollment
7) Locally advanced disease demonstrated by pelvic examination preferably performed under anesthesia
8) Previous or concurrent muscle invasive or disseminated/metastatic bladder cancer
9) Prior treatment with an anti-PD-1, anti-programmed death ligand 1 (PD-L1), anti-PD-L2, or anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
10) Prior treatment with BMS-986205 or any other IDO1 inhibitors
11) Prior systemic chemotherapy or immunotherapy. Intravesical chemotherapy and/or interferon administered prior to the date of tumor sample submission is permitted.
12) Prior radiation therapy for bladder cancer
13) Prior surgery for bladder cancer other than TURBT and/or bladder biopsies
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method