A Phase 2 Study of Nivolumab or Nivolumab/BMS-986205 Alone or Combined with Intravesical BCG in Participants with Bladder Cancer

Phase 1

Conditions: BCG-Unresponsive, High-Risk, Non-Muscle Invasive Bladder Cancer
MedDRA version: 20.0Level: PTClassification code 10005005Term: Bladder cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2017-003581-27-ES

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

Inclusion Criteria

-) 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).
-)Predominant histologic component (> 50%) must be urothelial (transitional cell) carcinoma
-) Must have undergone each of the following procedures within 8 weeks (56 days) of randomization:
a) 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.
b) 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.
c) 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 addition, the presence of
any suspicious lesions must be recorded and these lesions will be biopsied.
d) 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.
e) Computed tomography (CT) scan of the chest and CT or magnetic resonance imaging (MRI) of the abdomen and 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
f) Participants should either be deemed medically unfit for radical cystectomy, or should have refused radical cystectomy after consultation with their urologist or oncologist. Participants may be deemed medically unfit for radical cystectomy due to comorbid conditions with a risk of mortality from radical cystectomy = 5% as estimated by the American College of Surgeons risk calculator using the current procedure terminology code 51595 or 51596 for cystectomy
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 144
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 336

Exclusion Criteria

-) Women who are pregnant or breastfeeding
-) 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.
-) Participants with a history of glucose-6-phosphate dehydrogenase deficiency or other congenital or autoimmune hemolytic disorders.
-) Evidence of locally advanced or metastatic bladder cancer as seen in cross-sectional imaging of the chest, abdomen, and pelvis
-) UC in the upper genitourinary tract (kidneys, renal collecting systems, ureters) within 24 months of enrollment
-) UC and/or CIS in the prostatic urethra within 12 months of enrollment
-) Locally advanced disease demonstrated by pelvic examination preferably performed under anesthesia
-) Previous or concurrent muscle invasive or disseminated/metastatic bladder cancer
-) 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
-) Prior treatment with BMS-986205 or any other IDO1 inhibitors
-) Prior systemic chemotherapy or immunotherapy. Intravesical chemotherapy and/or interferon administered prior to the date of tumor sample submission is permitted.
-) Prior radiation therapy for bladder cancer
-) 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

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