Nivolumab (BMS-936558; MDX-1106) in Combination With Sunitinib, Pazopanib, or Ipilimumab in Subjects With Metastatic Renal Cell Carcinoma (RCC) (CheckMate 016)
- Conditions
- Renal Cell CarcinomaClear-cell Metastatic Renal Cell Carcinoma
- Interventions
- Registration Number
- NCT01472081
- Lead Sponsor
- Bristol-Myers Squibb
- 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 available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 194
-
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:
- 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
- Only prior cytokine based treatment for metastatic RCC [eg, interferon-alpha (IFN-alpha) or interleukin 2 (IL-2)] as prior therapy is allowed
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm P: Nivolumab + Pazopanib 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 Arm P: Nivolumab + Pazopanib Nivolumab 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 Arm S: Nivolumab + Sunitinib Nivolumab 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 Arm I-3: Nivolumab + Ipilimumab Nivolumab 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 Arm I-1: Nivolumab + Ipilimumab 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 Arm IN-3: Nivolumab+Ipilimumab 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 Arm I-1: Nivolumab + Ipilimumab Nivolumab 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 Arm I-3: Nivolumab + Ipilimumab 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 Arm IN-3: Nivolumab+Ipilimumab Nivolumab 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 Arm S: Nivolumab + Sunitinib 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
- Primary Outcome Measures
Name Time Method Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation 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.
- Secondary Outcome Measures
Name Time Method Rate of Progression-free Survival (PFS) at Week 24 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.
Duration of Response (DOR) 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).
Best Overall Response Rate (BOR) 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) 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.Progression-free Survival (PFS) 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.
Trial Locations
- Locations (14)
City Of Hope
🇺🇸Duarte, California, United States
Memorial Sloan Kettering Nassau
🇺🇸New York, New York, United States
Blumenthal Cancer Center
🇺🇸Charlotte, North Carolina, United States
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
BC Cancer Agency - Vancouver Centre
🇨🇦Vancouver, British Columbia, Canada
Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Tennessee Oncology, PLLC
🇺🇸Nashville, Tennessee, United States
University Of Texas M.D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada