MedPath

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

Phase 2
Completed
Conditions
Various Advanced Cancer
Interventions
Registration Number
NCT02387996
Lead Sponsor
Bristol-Myers Squibb
Brief 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
270
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
NivolumabNivolumabNivolumab intravenous infusion as specified
Primary Outcome Measures
NameTimeMethod
ORR Per BIRC Assessment by PD-L1 Expression LevelFrom 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)

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

Time to Response (TTR)From first dosing date to the date of the first confirmed response (up to approximately 14 months)

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.

Duration of Response (DOR)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)

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.

Objective Response Rate Per BIRC AssessmentFrom 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)

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

Secondary Outcome Measures
NameTimeMethod
Overall Survival (OS)From first dosing date to the date of death (up to approximately 23 months)

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.

Progression Free Survival (PFS)From first dosing date to the date of the first documented tumor progression (up to approximately 6 months)

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.

Objective Response Rate (ORR) Per InvestigatorFrom 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)

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.

Trial Locations

Locations (64)

Local Institution - 0012

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Duarte, California, United States

Local Institution - 0052

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Iowa City, Iowa, United States

Crescent City Research Consortium, LLC

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Marrero, Louisiana, United States

GU Research Network, LLC

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Omaha, Nebraska, United States

Local Institution - 0028

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New York, New York, United States

Local Institution - 0051

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Portland, Oregon, United States

Local Institution - 0060

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Waratah, New South Wales, Australia

Local Institution - 0022

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Brussels, Belgium

Local Institution - 0027

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Brno, Czechia

Local Institution - 0026

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Olomouc, Czechia

Local Institution

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Gdansk, Poland

Local Institution - 0009

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Tampere, Finland

Local Institution - 0049

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Erfurt, Germany

Local Institution - 0047

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Erlangen, Germany

Local Institution - 0042

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Hamburg, Germany

Local Institution - 0041

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Muenchen, Germany

Local Institution - 0043

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Heidelberg, Germany

Local Institution - 0048

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Tuebingen, Germany

Local Institution - 0017

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Arezzo, Italy

Local Institution - 0018

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Napoli, Italy

Local Institution - 0050

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Pavia, Italy

Local Institution - 0021

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Roma, Italy

Local Institution - 0074

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Akita-shi, Akita, Japan

Local Institution - 0083

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Hirosaki-shi, Aomori, Japan

Local Institution - 0081

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Tsukuba-shi, Ibaraki, Japan

Local Institution - 0078

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Morioka-shi, Iwate, Japan

Local Institution - 0080

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Kumamoto-shi, Kumamoto, Japan

Local Institution - 0082

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Kyoto-shi, Kyoto, Japan

Local Institution - 0076

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Niigata-shi, Niigata, Japan

Local Institution - 0084

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Osaka-Sayama-Shi, Osaka, Japan

Local Institution - 0085

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Bunkyo-ku, Tokyo, Japan

Local Institution - 0073

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Bunkyo-ku, Tokyo, Japan

Local Institution - 0077

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Bunkyo-ku, Tokyo, Japan

Local Institution - 0086

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Shinjuku-ku, Tokyo, Japan

Local Institution - 0075

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Shinjuku-ku, Tokyo, Japan

Local Institution - 0046

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Krakow, Poland

Local Institution - 0056

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Szczecin, Poland

Local Institution - 0040

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Lodz, Poland

Local Institution - 0035

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Badalona-barcelona, Spain

Local Institution - 0038

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Wroclaw, Poland

Local Institution - 0034

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Hospitalet de Llobregat - Barcelona, Spain

Local Institution - 0033

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Barcelona, Spain

Local Institution - 0031

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Madrid, Spain

Local Institution - 0014

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Lund, Sweden

Local Institution - 0032

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Sevilla, Spain

Local Institution - 0059

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Pittsburgh, Pennsylvania, United States

Local Institution - 0001

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Houston, Texas, United States

University Cancer Blood Ctr

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Athens, Georgia, United States

Ft. Wayne Med Onco-Hema Inc

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Fort Wayne, Indiana, United States

Local Institution - 0004

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Charlotte, North Carolina, United States

Local Institution - 0029

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Philadelphia, Pennsylvania, United States

Local Institution - 0036

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Seattle, Washington, United States

Local Institution - 0010

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Helsinki, Finland

Local Institution - 0016

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Aurora, Colorado, United States

Local Institution - 0013

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Phoenix, Arizona, United States

Pacific Hematology Oncology Associates

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San Francisco, California, United States

Local Institution - 0030

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Indianapolis, Indiana, United States

Karmanos Cancer Institute

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Detroit, Michigan, United States

Local Institution - 0020

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Milano, Italy

Local Institution - 0070

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Elizabeth Vale, South Australia, Australia

Local Institution - 0024

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Hasselt, Belgium

Erlanger Oncology & Hematology - Univ. of TN

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Chattanooga, Tennessee, United States

Local Institution - 0023

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Edegem, Belgium

Local Institution - 0015

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Jena, Germany

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