A Study of Nivolumab in Participants With Metastatic or Unresectable Bladder Cancer

Various Advanced Cancer Clinical Trial

Official title:

A Phase II Single Arm Clinical Trial of Nivolumab (BMS-936558) in Subjects With Metastatic or Unresectable Urothelial Cancer Who Have Progressed or Recurred Following Treatment With a Platinum Agent

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02387996
• Other study ID #: CA209-275
• Status: Completed
• Phase: Phase 2
• Start date: March 9, 2015
• Est. completion date: November 12, 2021

Study information

• Verified date: October 2022
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose the study is to measure the effect of nivolumab (BMS-936558) in reducing tumor size in subjects with metastatic or unresectable bladder cancer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 270
• Est. completion date: November 12, 2021
• Est. primary completion date: April 15, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Evidence of metastatic or surgically unresectable transitional cell carcinoma of the urothelium involving the bladder,urethra,ureter or renal pelvis
• Measurable disease by CT or MRI
• Progression or recurrence after treatment
• i) With at least 1 platinum-containing chemotherapy regimen for metastatic or surgically unresectable locally advanced urothelial cancer, or
• ii) Within 12 months of peri-operative (neo-adjuvant or adjuvant) treatment with a platinum agent in the setting of cystectomy for localized muscle-invasive urothelial cancer
• Subject that have received more than 2 prior lines of chemotherapy must not have liver metastases
• Tumor tissues (archived or new biopsy) must be provided for biomarker analysis
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

Exclusion Criteria:

• Subjects with active cancer that has spread to the central nervous system
• Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured
• Subject with active, known or suspected autoimmune disease
• Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 day of study drug administration
• Prior treatment with an anti-PD-1,anti-PD-L1,anti-PD-L2,anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody, anti-CD137 or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways

Exclusion laboratory criteria:

• Positive test for hepatitis B virus surface antigen (HBV s Ag) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
• Known history of testing positive for human Immunodeficiency virus (HIV) or known acquired Immunodeficiency syndrome (AIDS) Other protocol-defined inclusion/exclusion criteria apply

Related Conditions & MeSH terms

• Various Advanced Cancer

Intervention

Drug:
• Nivolumab

Locations

Country	Name	City	State
Australia	Local Institution - 0070	Elizabeth Vale	South Australia
Australia	Local Institution - 0060	Waratah	New South Wales
Belgium	Local Institution - 0022	Brussels
Belgium	Local Institution - 0023	Edegem
Belgium	Local Institution - 0024	Hasselt
Czechia	Local Institution - 0027	Brno
Czechia	Local Institution - 0026	Olomouc
Czechia	Local Institution	Praha 5
Finland	Local Institution - 0010	Helsinki
Finland	Local Institution - 0009	Tampere
Germany	Local Institution - 0049	Erfurt
Germany	Local Institution - 0047	Erlangen
Germany	Local Institution - 0042	Hamburg
Germany	Local Institution - 0043	Heidelberg
Germany	Local Institution - 0015	Jena
Germany	Local Institution - 0041	Muenchen
Germany	Local Institution	Rostock
Germany	Local Institution - 0048	Tuebingen
Italy	Local Institution - 0017	Arezzo
Italy	Local Institution - 0020	Milano
Italy	Local Institution - 0018	Napoli
Italy	Local Institution - 0050	Pavia
Italy	Local Institution - 0021	Roma
Japan	Local Institution - 0074	Akita-shi	Akita
Japan	Local Institution - 0073	Bunkyo-ku	Tokyo
Japan	Local Institution - 0077	Bunkyo-ku	Tokyo
Japan	Local Institution - 0085	Bunkyo-ku	Tokyo
Japan	Local Institution - 0083	Hirosaki-shi	Aomori
Japan	Local Institution - 0080	Kumamoto-shi	Kumamoto
Japan	Local Institution - 0082	Kyoto-shi	Kyoto
Japan	Local Institution - 0078	Morioka-shi	Iwate
Japan	Local Institution - 0076	Niigata-shi	Niigata
Japan	Local Institution - 0084	Osaka-Sayama-Shi	Osaka
Japan	Local Institution - 0075	Shinjuku-ku	Tokyo
Japan	Local Institution - 0086	Shinjuku-ku	Tokyo
Japan	Local Institution - 0081	Tsukuba-shi	Ibaraki
Japan	Local Institution	Yokohama	Kanagawa
Poland	Local Institution	Gdansk
Poland	Local Institution - 0046	Krakow
Poland	Local Institution - 0040	Lodz
Poland	Local Institution - 0056	Szczecin
Poland	Local Institution - 0038	Wroclaw
Spain	Local Institution - 0035	Badalona-barcelona
Spain	Local Institution - 0033	Barcelona
Spain	Local Institution - 0034	Hospitalet de Llobregat - Barcelona
Spain	Local Institution - 0031	Madrid
Spain	Local Institution - 0032	Sevilla
Sweden	Local Institution - 0014	Lund
United States	University Cancer Blood Ctr	Athens	Georgia
United States	Local Institution - 0016	Aurora	Colorado
United States	Local Institution - 0004	Charlotte	North Carolina
United States	Erlanger Oncology & Hematology - Univ. of TN	Chattanooga	Tennessee
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Local Institution - 0012	Duarte	California
United States	Ft. Wayne Med Onco-Hema Inc	Fort Wayne	Indiana
United States	Local Institution - 0001	Houston	Texas
United States	Local Institution - 0030	Indianapolis	Indiana
United States	Local Institution - 0052	Iowa City	Iowa
United States	Crescent City Research Consortium, LLC	Marrero	Louisiana
United States	Local Institution - 0028	New York	New York
United States	GU Research Network, LLC	Omaha	Nebraska
United States	Local Institution - 0029	Philadelphia	Pennsylvania
United States	Local Institution - 0013	Phoenix	Arizona
United States	Local Institution - 0059	Pittsburgh	Pennsylvania
United States	Local Institution - 0051	Portland	Oregon
United States	Pacific Hematology Oncology Associates	San Francisco	California
United States	Local Institution - 0036	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Ono Pharmaceutical Co. Ltd

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Czechia,  Finland,  Germany,  Italy,  Japan,  Poland,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate Per BIRC Assessment	Objective Response Rate (ORR) was defined as the number of participants with a best overall response of confirmed Complete Response (CR) or Partial Response (PR) (per RECIST 1.1 criteria) divided by the number of all treated participants. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors. CR= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. BIRC= blinded independent review committee	From the date of first dose to the date of objectively documented progression or the date of subsequent therapy, whichever occurs first (assessed up to 14 months)
Primary	ORR Per BIRC Assessment by PD-L1 Expression Level	Objective Response Rate (ORR) was defined as the number of participants with a best overall response of confirmed Complete Response (CR) or Partial Response (PR) (per RECIST 1.1 criteria) divided by the number of all treated participants. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors. CR= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. BIRC= blinded independent review committee PD-L1 expression level= membranous staining in greater than or equal to 5% and greater than or equal to 1% tumor cells. n = Number of participants in each category	From the date of first dose to the date of objectively documented progression or the date of subsequent therapy, whichever occurs first (assessed up to 14 months)
Primary	Time to Response (TTR)	TTR is defined as the time from first dosing date to the date of the first confirmed complete response (CR) or partial response (PR), as assessed by the Blinded Independent Review Committee (BIRC). Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	From first dosing date to the date of the first confirmed response (up to approximately 14 months)
Primary	Duration of Response (DOR)	DOR is defined as the time from first confirmed response, complete response (CR) or partial response (PR) to the date of the first documented tumor progression as determined using RECIST 1.1 criteria or death due to any cause, whichever occurs first. Participants who start subsequent therapy without a prior reported progression will be censored at the last evaluable tumor assessments prior to initiation of the subsequent anticancer therapy. Participants who die without a reported prior progression will be considered to have progressed on the date of their death. Participants who neither progress nor die will be censored on the date of their last evaluable tumor assessment.	From the first confirmed response to the date of the first documented tumor progression or death due to any cause, whichever occurs first (up to approximately 14 months)
Secondary	Progression Free Survival (PFS)	PFS was defined as the time from first dosing date to the date of the first documented tumor progression, based on Blinded Independent Review Committee (BIRC) assessments or death due to any cause. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. PD-L1 expression level is defined as membranous staining in greater than or equal to 5% and greater than or equal to 1% tumor cells.	From first dosing date to the date of the first documented tumor progression (up to approximately 6 months)
Secondary	Overall Survival (OS)	Overall Survival was defined as the time from first dosing date to the date of death. A participant who had not died was censored at last known date alive. PD-L1 expression level = membranous staining in greater than or equal to 5% and greater than or equal to 1% tumor cells.	From first dosing date to the date of death (up to approximately 23 months)
Secondary	Objective Response Rate (ORR) Per Investigator	Investigator-assessed ORR was defined as the percent of participants with a best overall response of confirmed complete response (CR) or partial response (PR). Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD-L1 expression level = Membranous staining in greater than or equal to 5% and greater than or equal to 1% tumor cells.	From the date of first dose to the date of objectively documented progression or the date of subsequent therapy, whichever occurs first (up to approximately 45 months)

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting