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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01721746
Recruitment Status : Active, not recruiting
First Posted : November 6, 2012
Results First Posted : March 22, 2017
Last Update Posted : July 8, 2020
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE November 2, 2012
First Posted Date  ICMJE November 6, 2012
Results First Submitted Date  ICMJE February 1, 2017
Results First Posted Date  ICMJE March 22, 2017
Last Update Posted Date July 8, 2020
Actual Study Start Date  ICMJE December 13, 2012
Actual Primary Completion Date February 16, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 4, 2017)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 2, 2012)
  • Objective response rate (ORR) of BMS-936558 in subjects with advanced melanoma [ Time Frame: 23 months ]
    ORR is defined as the number of subjects with a Best Overall Response (BOR) of complete response (CR) or partial response (PR) divided by the number of randomized subjects
  • Overall survival(OS) of BMS-936558 in subjects with advanced melanoma [ Time Frame: 23 months ]
    Overall Survival (OS) is defined the time between the date of randomization to the date of death
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 4, 2017)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 2, 2012)
  • Progression-free survival (PFS) [ Time Frame: 23 months ]
    PFS is defined as the time from randomization to the date of the first documented progression or death due to any cause, whichever occurs first
  • Programmed death-ligand 1 (PD-L1) expression [ Time Frame: 23 months ]
    To evaluate whether PD-L1 expression is a predictive biomarker for ORR and OS by testing the interaction between PD-L1 expression and treatment arms
  • Health Related Quality of Life (HRQoL) [ Time Frame: Baseline (Day1) and 23 months ]
    HRQoL will be measured by mean changes from screening/baseline in the EORTC QLQ-C30 global health status/QoL composite scale and by mean changes from screening/baseline in the remaining EORTC QLQ-C30 scales in all randomized subjects
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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)
Official Title  ICMJE 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
Brief Summary 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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Unresectable or Metastatic Melanoma
Intervention  ICMJE
  • Biological: BMS-936558
  • Drug: Dacarbazine
    Other Names:
    • DTIC-Dome
    • DTIC
  • Drug: Carboplatin
    Other Names:
    • Paraplatin
    • CBDCA
  • Drug: Paclitaxel
    Other Name: Onxol
Study Arms  ICMJE
  • 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
    Intervention: 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

    Interventions:
    • Drug: Dacarbazine
    • Drug: Carboplatin
    • Drug: Paclitaxel
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 1, 2017)
631
Original Estimated Enrollment  ICMJE
 (submitted: November 2, 2012)
390
Estimated Study Completion Date  ICMJE November 13, 2020
Actual Primary Completion Date February 16, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Belgium,   Brazil,   Canada,   Denmark,   France,   Germany,   Israel,   Italy,   Netherlands,   Spain,   Switzerland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01721746
Other Study ID Numbers  ICMJE CA209-037
2012-001828-35 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bristol-Myers Squibb
Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP