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Nivolumab (BMS-936558; MDX-1106) in Combination With Sunitinib, Pazopanib, or Ipilimumab in Subjects With Metastatic Renal Cell Carcinoma (RCC) (CheckMate 016)

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: NCT01472081
Recruitment Status : Active, not recruiting
First Posted : November 16, 2011
Results First Posted : August 2, 2019
Last Update Posted : April 22, 2020
Sponsor:
Collaborator:
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE October 26, 2011
First Posted Date  ICMJE November 16, 2011
Results First Submitted Date  ICMJE May 23, 2018
Results First Posted Date  ICMJE August 2, 2019
Last Update Posted Date April 22, 2020
Actual Study Start Date  ICMJE January 25, 2012
Actual Primary Completion Date February 2, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 12, 2019)
Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation [ Time Frame: From date of first dose to date of last dose plus 100 days (assessed up to March 2016, approximately 49 months) ]
Safety assessments by treatment arm and dose level were based on incidence of AEs, and the incidence of serious adverse events (SAEs). AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling.
Original Primary Outcome Measures  ICMJE
 (submitted: November 11, 2011)
  • Safety and tolerability of BMS-936558 plus Sunitinib or Pazopanib measured by incidence of Adverse event (AE) [ Time Frame: up to 30 days after last dose or longer ]
  • Safety and tolerability of BMS-936558 plus Sunitinib or Pazopanib measured by incidence of Serious adverse event (SAE) [ Time Frame: up to 90 days after last dose or longer ]
  • Safety and tolerability of BMS-936558 plus Sunitinib or Pazopanib measured by incidence of lab abnormality [ Time Frame: Within 28 days prior to first dose ]
  • Safety and tolerability of BMS-936558 plus Sunitinib or Pazopanib measured by incidence of lab abnormality [ Time Frame: Day 1 of Cycles 1-4 ]
  • Safety and tolerability of BMS-936558 plus Sunitinib or Pazopanib measured by incidence of lab abnormality [ Time Frame: Day 8 of Cycles 1-4 ]
  • Safety and tolerability of BMS-936558 plus Sunitinib or Pazopanib measured by incidence of lab abnormality [ Time Frame: Day 22 of Cycles 1-4 ]
  • Safety and tolerability of BMS-936558 plus Sunitinib or Pazopanib measured by incidence of lab abnormality [ Time Frame: Day 29 of Cycles 1-4 ]
  • Safety and tolerability of BMS-936558 plus Sunitinib or Pazopanib measured by incidence of lab abnormality [ Time Frame: Day 1 of Cycles 5+ ]
  • Safety and tolerability of BMS-936558 plus Sunitinib or Pazopanib measured by incidence of lab abnormality [ Time Frame: Day 22 of Cycles 5+ ]
  • Safety and tolerability of BMS-936558 plus Sunitinib or Pazopanib measured by incidence of lab abnormality [ Time Frame: 21 days (average) after last dose ]
  • Safety and tolerability of BMS-936558 plus Sunitinib or Pazopanib measured by incidence of lab abnormality [ Time Frame: Follow-up visit 56 days after last dose ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 12, 2019)
  • Best Overall Response Rate (BOR) [ Time Frame: From date of first dose to date of disease progression or subsequent anti-cancer therapy, whichever occurred first (assessed up to March 2016, approximately 49 months) ]
    BOR was defined as the best response designation over the study as a whole, recorded between the date of first dose of study medication and the date of objectively documented progression per RECIST 1.1 criteria or the date of subsequent anti-cancer therapy, whichever occurred first. CR = Disappearance of all target lesions. Any pathological lymph nodes 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. PD = At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. SD = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
  • Objective Response Rate (ORR) [ Time Frame: From date of first dose to interim analysis (Assessed up to March 2016, approximately 49 months) ]
    ORR was defined as the proportion of participants who achieved a BOR of either complete response (CR) or partial response (PR) in the population of interest. 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.
  • Duration of Response (DOR) [ Time Frame: From date of first dose to date of disease progression or death, whichever occurred first (assessed up to March 2016, approximately 49 months) ]
    DOR was computed for participants with BOR of CR or PR only, and defined as the time between the date of first documented objective response and the date of the first subsequent disease progression or death. Participants who remained alive and had not progressed were censored on the last tumor assessment date (prior to subsequent cancer therapy).
  • Rate of Progression-free Survival (PFS) at Week 24 [ Time Frame: 24 weeks ]
    Rate of PFS at week 24 was defined as the proportion of participants remaining progression free or surviving at 24 weeks, calculated by the product-limit method (Kaplan-Meier estimate) which took into account censored data. Participants who did not have any on-study tumor assessment and did not die were censored on the date of first dose of study medication.
  • Progression-free Survival (PFS) [ Time Frame: From date of first dose to date of disease progression or death, whichever occurred first (assessed up to March 2016, approximately 49 months) ]
    PFS was defined as the time from the date of first dose of study medication to the date of first disease progression or death. Participants who did not have any on-study tumor assessment and did not die were censored on the date of first dose of study medication.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 11, 2011)
  • Antitumor activity of BMS-936558 plus Sunitinib or Pazopanib measured by Objective Response Rate (ORR) [ Time Frame: Every 6 weeks for first 4 assessments, then every 12 weeks until disease progression ]
  • Antitumor activity of BMS-936558 plus Sunitinib or Pazopanib measured by duration of response according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 [ Time Frame: Every 6 weeks for first 4 assessments, then every 12 weeks until disease progression ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nivolumab (BMS-936558; MDX-1106) in Combination With Sunitinib, Pazopanib, or Ipilimumab in Subjects With Metastatic Renal Cell Carcinoma (RCC) (CheckMate 016)
Official Title  ICMJE A Phase 1 Study of Nivolumab (BMS-936558) Plus Sunitinib, Pazopanib or Ipilimumab in Subjects With Metastatic Renal Cell Carcinoma
Brief Summary The purpose is to determine the safety, effectiveness and best dose to use when giving Nivolumab in combination with Sunitinib, Pazopanib, or Ipilimumab for the treatment of metastatic renal cell carcinoma.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Renal Cell Carcinoma
  • Clear-cell Metastatic Renal Cell Carcinoma
Intervention  ICMJE
  • Biological: Nivolumab
    Other Name: BMS-936558 (MDX-1106)
  • Biological: Pazopanib
    Other Name: Votrient (Pazopanib hydrochloride)
  • Drug: Sunitinib
    Other Names:
    • Sutent®
    • Sunitinib Malate
  • Biological: Ipilimumab
    Other Name: YERVOY™
Study Arms  ICMJE
  • Experimental: Arm S: Nivolumab + Sunitinib

    Nivolumab 0.3, 2.0 (starting dose), 5.0 mg/kg solution intravenously every 21 days until Progressive disease (PD), toxicity or discontinue for other reasons

    Sunitinib 50 mg capsule by mouth on Days 1-28 of 42 day cycle until Progressive disease (PD), toxicity or discontinue for other reasons

    Interventions:
    • Biological: Nivolumab
    • Drug: Sunitinib
  • Experimental: Arm P: Nivolumab + Pazopanib

    Nivolumab 0.3, 2.0 (starting dose), 5.0 mg/kg solution intravenously every 21 days until Progressive disease (PD), toxicity or discontinue for other reasons

    Pazopanib 800 mg tablet by mouth daily until Progressive disease (PD), toxicity or discontinue for other reasons

    Interventions:
    • Biological: Nivolumab
    • Biological: Pazopanib
  • Experimental: Arm I-1: Nivolumab + Ipilimumab

    Nivolumab 3 mg/kg solution intravenously (IV) every 21 days during Induction phase and every 14 days during Maintenance phase until Progressive disease (PD), toxicity or discontinue for other reasons

    Ipilimumab 1mg/kg solution intravenously (IV) every 21 days during Induction phase (Ipilimumab will not be administered during Maintenance phase) until Progressive disease (PD), toxicity or discontinue for other reasons

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
  • Experimental: Arm I-3: Nivolumab + Ipilimumab

    Nivolumab 1mg/kg solution intravenously (IV) every 21 days during Induction phase and 3mg/kg solution intravenously (IV) every 14 days during Maintenance phase

    Ipilimumab 3mg/kg solution intravenously (IV) every 21 days during Induction phase. Ipilimumab will not be administered during Maintenance phase

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
  • Experimental: Arm IN-3: Nivolumab+Ipilimumab

    Nivolumab 3mg/kg solution intravenously (IV) every 21 days during Induction phase and 3mg/kg solution intravenously (IV) every 14 days during Maintenance phase

    Ipilimumab 3mg/kg solution intravenously (IV) every 21 days during Induction phase. Ipilimumab will not be administered during Maintenance phase

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
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: June 12, 2019)
194
Original Estimated Enrollment  ICMJE
 (submitted: November 11, 2011)
72
Estimated Study Completion Date  ICMJE June 30, 2021
Actual Primary Completion Date February 2, 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:

  • Subjects with histological confirmation of RCC
  • Advanced or metastatic disease
  • Measurable disease as defined by RECIST 1.1 criteria
  • Karnofsky Performance Status (KPS) ≥80%
  • Available tumor tissue (archival or recent acquisition)
  • Subjects enrolled in the I-1, I-3 expansion arms and IN-3 addition arms must not have received any prior systemic therapy for RCC with the following exceptions:

    1. One prior adjuvant or neoadjuvant therapy for localized or locally advanced RCC is allowed provided recurrence occurred ≥ 6 months after the last dose of the adjuvant or neoadjuvant therapy
    2. Only prior cytokine based treatment for metastatic RCC [eg, interferon-alpha (IFN-alpha) or interleukin 2 (IL-2)] as prior therapy is allowed

Exclusion Criteria:

  • Active central nervous system (CNS) metastases
  • Active or history of autoimmune disease
  • Ongoing symptomatic cardiac dysrhythmias or uncontrolled atrial fibrillation
  • History of cerebrovascular accident including transient ischemic attack within the past 12 months
  • History of pulmonary embolism or deep vein thrombosis (DVT) within the past 6 months
  • Chronic systemic steroids (>10 mg/day Prednisone equivalents) or any other immunosuppressive agents
  • White blood cell (WBC) <2,000/mm3
  • Neutrophiles <1,500/mm3
  • Platelets <100,000/mm3
  • Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) >3x upper limit of normal (ULN)
  • Total Bilirubin >1.5x ULN (except subjects with Gilbert syndrome, total bilirubin <3.0 mg/dL)
  • Cardiac ejection fraction <LLN (lower limit of normal)
  • Serum creatinine >1.5x ULN or creatinine clearance <40 mL/min (Cockroft-Gault formula)

Exclusion Criteria for Arm S and Arm P only:

  • For dose escalation cohorts - subjects who received prior Sunitinib or Pazopanib and required permanent discontinuation due to toxicity or required dose reduction or delay during the first 12 weeks of therapy due to toxicity, or received both prior Sunitinib and Pazopanib
  • Poorly controlled hypertension
  • Active bleeding or bleeding susceptibility
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 Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01472081
Other Study ID Numbers  ICMJE CA209-016
Has Data Monitoring Committee No
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 Ono Pharmaceutical Co. Ltd
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date April 2020

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