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A Study to Compare BMS-936558 to the Physician's Choice of Either Dacarbazine or Carboplatin and Paclitaxel in Advanced Melanoma Patients That Have Progressed Following Anti-CTLA-4 Therapy (CheckMate 037)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01721746
First received: November 2, 2012
Last updated: April 4, 2017
Last verified: April 2017
  Purpose
The purpose of the study is to estimate the response rate and compare overall survival of patients taking BMS-936558 to those taking study physician's choice of either Dacarbazine or Carboplatin and Paclitaxel

Condition Intervention Phase
Unresectable or Metastatic Melanoma Biological: BMS-936558 Drug: Dacarbazine Drug: Carboplatin Drug: Paclitaxel Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Randomized Open-Label Phase 3 Trial of BMS-936558 (Nivolumab) Versus Investigator's Choice in Advanced (Unresectable or Metastatic) Melanoma Patients Progressing Post Anti-CTLA-4 Therapy

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Objective Response Rate (ORR) [ Time Frame: From date of randomization to the date of objectively documented progression, date of death, or the date of subsequent therapy; approx. 16 months ]
    ORR=number of participants with a Best Overall Response (BOR) of complete response (CR) or partial response (PR) divided by the number of randomized participants and reported as a percentage. BOR was defined as the best response designation, as determined by the independent review committee (IRC), recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of subsequent therapy (including tumor-directed radiotherapy and tumor-directed surgery), whichever occurred first. For participants without documented progression or subsequent therapy, all available response designations contributed to the BOR assessment. 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. Analysis made at Primary Endpoint; Study On-going

  • Median Overall Survival (OS) at Primary Endpoint [ Time Frame: From the date of randomization to the date of death; up to 37 months ]
    Overall Survival (OS) was defined the time between the date of randomization to the date of death. For participants without documentation of death, OS was censored on the last date the participant was known to be alive. OS was followed continuously while participants were on the study drug and every 3 months via in-person or phone contact after participants discontinued the study drug. This interim OS analysis was performed on all randomized subjects when at least 169 events had been observed. Analysis made at Primary Endpoint; Study On-going.


Secondary Outcome Measures:
  • Median Months of Progression-free Survival (PFS) Per Independent Radiology Review Committee (IRC/IRRC) [ Time Frame: From the date of randomization to the date of the first documented progression or death; up to 37 months ]
    PFS=time from randomization to the date of the first documented progression or death due to any cause, whichever first. Participants who (1) died without a reported progression were considered to have progressed on the date of their death, (2) did not progress or die were censored on the date of their last evaluable tumor assessment, (3) did not have any on study tumor assessments and did not die were censored on the date they were randomized, and (4) started any subsequent anti-cancer therapy (including tumor-directed radiotherapy or surgery) without a prior reported progression were censored at the last evaluable tumor assessment prior to or upon initiation of the subsequent anti-cancer therapy. Per RECIST 1.1, progression is >= 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes baseline sum if smallest on study). The sum must demonstrate an absolute increase of >= 5 mm. Analysis made at Primary Endpoint; Study On-going

  • Objective Response Rate (ORR) by Baseline PD-L1 Expression [ Time Frame: From date of randomization to the date of objectively documented progression or the date of subsequent therapy; approx. 16 months ]
    PD-L1 expression evaluated as a predictive biomarker for ORR by analyzing the interaction between PD-L1 expression and treatment arms. Randomized participants with an Indeterminate PD-L1 result per the verified assay were categorized as "Subjects without Tumor Tissue Samples". ORR=number of participants with a Best Overall Response (BOR) of complete response (CR) or partial response (PR) divided by number of randomized participants and reported as a percentage. Analysis made at Primary Endpoint; Study On-going.

  • Median Overall Survival (OS) Time in Months by Baseline PD-L1 Expression [ Time Frame: From the date of randomization to the date of death; up to 37 months ]
    PD-L1 expression evaluated as a predictive biomarker for OS by analyzing the interaction between PD-L1 expression and treatment arms. Randomized participants with an Indeterminate PD-L1 result per the verified assay were categorized as "Subjects without Tumor Tissue Samples". Overall Survival (OS) was defined the time between the date of randomization to the date of death. For participants without documentation of death, OS was censored on the last date the participant was known to be alive. OS was followed continuously while participants were on the study drug and every 3 months via in-person or phone contact after participants discontinued the study drug. The interim OS analysis was performed on all randomized subjects when at least 169 events had been observed. Analysis made at Primary Endpoint; Study On-going.

  • Mean Change From Baseline in Health-related Quality of Life (HRQoL) Global Health Status Scores [ Time Frame: From Baseline (Day1) to second Follow-Up; up to 37 months ]
    Health-related Quality of Life (HRQoL) was assessed with the EORTC QLQ-C30 questionnaire, which is the most commonly used quality-of-life instrument in oncology trials. The instrument's 30 items were divided among 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties), and a global health/quality of life scale. Raw scores for the EORTC QLQ-C30 were transformed to a 0-100 metric. Higher scores for all functional scales and Global Health Status=better HRQoL; an increase from baseline indicates improvement in HRQoL. Lower scores for symptom scales=better HRQoL; a decline from baseline for symptom scales =improvement in symptoms compared to baseline. A 10 point difference on a 100 point scale between treatments was considered clinically significant.


Enrollment: 631
Study Start Date: December 2012
Estimated Study Completion Date: September 2018
Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BMS-936558 3 mg/kg (IV)
BMS-936558 3 mg/kg solution for injection by intravenous (IV), every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
Biological: BMS-936558
Active Comparator: Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)

Dacarbazine: 1000mg/m2, Powder for IV solution, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Carboplatin: Area under the concentration-time curve (AUC) 6, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Paclitaxel: 175 mg/ m2, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Drug: Dacarbazine
Other Names:
  • DTIC-Dome
  • DTIC
Drug: Carboplatin
Other Names:
  • Paraplatin
  • CBDCA
Drug: Paclitaxel
Other Name: Onxol

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

  • Men & women ≥ 18 years of age
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
  • Histologically confirmed Stage III (unresectable)/Stage IV melanoma
  • Measurable disease by computed tomography (CT)/magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
  • Objective evidence of disease progression (clinical or radiological) during or after at least 1 (V600 Wildtype) or at least 2 (V600 mutation positive) prior treatment regimens
  • Pre-treatment fresh core, excision or punch tumor biopsy
  • Archival Formalin-fixed paraffin-embedded (FFPE) tumor material if available

Exclusion Criteria:

  • Any treatment in a BMS-936558 (Nivolumab) trial
  • Subjects with condition requiring systemic treatment with either corticosteroids (> 10mg daily prednisone/equivalent) or other immunosuppressive medications within 14 days of study drug administration
  • Active, known or suspected autoimmune disease
  • Unknown BRAF status
  • Active brain metastasis or leptomeningeal metastasis
  • Ocular melanoma
  • Prior therapy with anti programmed death-1 (anti-PD-1), anti programmed death-ligand 1 (anti-PD-L1) or anti-programmed death-ligand 2 (anti-PD-L2)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01721746

  Hide Study Locations
Locations
United States, Arizona
Mayo Clinic
Scottsdale, Arizona, United States, 85259
United States, California
Ucsd Moores Cancer Center
La Jolla, California, United States, 92093
The Angeles Clinic & Research Institute
Los Angeles, California, United States, 90025
University Of California - Los Angeles
Los Angeles, California, United States, 90095
San Francisco Oncology Associates
San Francisco, California, United States, 94115
Ucsf Comprehensive Cancer Center
SanFrancisco, California, United States, 94143
United States, Colorado
University Of Colorado Cancer Center
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale University School Of Medicine
New Haven, Connecticut, United States, 06520
United States, Florida
Mount Sinai Medical Center
Miami Beach, Florida, United States, 33140
Orlando Health, Inc
Orlando, Florida, United States, 32806
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, United States, 33612
United States, Georgia
Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Michigan
University Of Michigan Health System
Ann Arbor, Michigan, United States, 48109
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Minnesota
Allina Health
Minneapolis, Minnesota, United States, 55407
United States, Missouri
Washington University School Of Medicine
Saint Louis, Missouri, United States, 63110
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Nyu Clinical Cancer Center
New York, New York, United States, 10016
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
Levine Cancer Institute
Charlotte, North Carolina, United States, 28204
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
University Hospitals Of Cleveland
Cleveland, Ohio, United States, 44106
United States, Oregon
Providence Oncology And Hematology
Portland, Oregon, United States, 97213
United States, Pennsylvania
Network Office Of Research And Innovation
Allentown, Pennsylvania, United States, 18103
St.Luke'S Cancer Center
Easton, Pennsylvania, United States, 18045
Hillman Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
Tennessee Oncology, Pllc
Nashville, Tennessee, United States, 37203
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Austria
Local Institution
Innsbruck, Austria, 6020
Local Institution
Wien, Austria, A-1090
Belgium
Local Institution
Brussels, Belgium, 1090
Local Institution
Bruxelles, Belgium, 1200
Local Institution
Edegem, Belgium, 2650
Local Institution
Leuven, Belgium, 3000
Brazil
Local Institution
Porto Alegre, Rio Grande do Sul, Brazil, 90035
Local Institution
Rio de Janeiro, Brazil, 20220
Local Institution
Sao Paulo, Brazil, 01321
Canada, Alberta
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Chum-Hopital Notre-Dame
Montreal, Quebec, Canada, H2L 4M1
Sir Mortimer B Davis - Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
Denmark
Aarhus Universitetshospital
Aarhus, Denmark, 8000
Herlev Hospital
Herlev, Denmark, 2730
Odense University Hospital
Odense, Denmark, 5000
France
Local Institution
Clermont Ferrand, France, 63003
Local Institution
Lille Cedex, France, 59037
Local Institution
Marseille, France, 13009
Local Institution
Nantes Cedex 1, France, 44093
Local Institution
Nice, France, 06200
Local Institution
Paris, France, 75010
Local Institution
Pierre Benite, France, 69310
Local Institution
Villejuif, France, 94805
Germany
Local Institution
Wuerzburg, Bayern, Germany, 97080
Local Institution
Buxtehude, Germany, 21614
Local Institution
Dresden, Germany, 01307
Local Institution
Essen, Germany, 45122
Local Institution
Frankfurt Am Main, Germany, 60590
Local Institution
Hannover, Germany, 30449
Local Institution
Heidelberg, Germany, 69120
Local Institution
Kiel, Germany, D-24105
Local Institution
Luebeck, Germany, 23538
Local Institution
Magdeburg, Germany, 39120
Local Institution
Munich, Germany, 81675
Local Institution
Tubingen, Germany, 72076
Israel
Local Institution
Jerusalem, Israel, 91120
Local Institution
Ramat Gan, Israel, 52621
Italy
Local Institution
Bari, Italy, 70124
Local Institution
Bergamo, Italy, 24127
Local Institution
Genova, Italy, 16132
Local Institution
Milano, Italy, 20133
Local Institution
Milano, Italy, 20141
Local Institution
Napoli, Italy, 80131
Local Institution
Padova, Italy, 35128
Local Institution
Roma, Italy, 00144
Local Institution
Siena, Italy, 53100
Netherlands
Local Institution
Amsterdam, Netherlands, 1066 CX
Local Institution
Groningen, Netherlands, 9713 GZ
Local Institution
Maastricht, Netherlands, 6229 HX
Spain
Local Institution
Barcelona, Spain, 08036
Local Institution
Barcelona, Spain, 08908
Local Institution
Madrid, Spain, 28020
Local Institution
Madrid, Spain, 28041
Local Institution
Pamplona, Spain, 31192
Local Institution
Valencia, Spain, 46014
Switzerland
Local Institution
Lausanne, Switzerland, 1011
Local Institution
Zurich, Switzerland, 8091
United Kingdom
Local Institution
Manchester, Greater Manchester, United Kingdom, M20 4BX
Local Institution
Southampton, Hampshire, United Kingdom, SO16 6YD
Local Institution
Oxford, Oxfordshire, United Kingdom, OX3 7LJ
Local Institution
London, Surrey, United Kingdom, SW3 6JJ
Local Institution
Newcastle Upon Tyne, Tyne And Wear, United Kingdom, NE7 7DN
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01721746     History of Changes
Other Study ID Numbers: CA209-037
2012-001828-35 ( EudraCT Number )
Study First Received: November 2, 2012
Results First Received: February 1, 2017
Last Updated: April 4, 2017

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Paclitaxel
Nivolumab
Albumin-Bound Paclitaxel
Carboplatin
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 23, 2017