Nivolumab (BMS-936558; MDX-1106) in Combination With Sunitinib, Pazopanib, or Ipilimumab in Subjects With Metastatic Renal Cell Carcinoma (RCC) (CheckMate 016)
Condition: Renal Cell Carcinoma; Clear-cell Metastatic Renal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: Nivolumab; Pazopanib; Sunitinib; Ipilimumab
Intervention MeSH terms: Nivolumab; Ipilimumab; Sunitinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 194.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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