Overview

This trial is active, not recruiting.

Conditions renal cell carcinoma, clear-cell metastatic renal cell carcinoma
Treatments nivolumab, pazopanib, sunitinib, ipilimumab
Phase phase 1
Targets VEGF, CTLA-4, PD-1, FLT-3, KIT, PDGF
Sponsor Bristol-Myers Squibb
Collaborator Ono Pharmaceutical Co. Ltd
Start date January 2012
End date February 2016
Trial size 175 participants
Trial identifier NCT01472081, CA209-016

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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
nivolumab BMS-936558 (MDX-1106)
sunitinib Sutent®
(Experimental)
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
nivolumab BMS-936558 (MDX-1106)
pazopanib Votrient (Pazopanib hydrochloride)
(Experimental)
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
nivolumab BMS-936558 (MDX-1106)
ipilimumab YERVOY™
(Experimental)
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
nivolumab BMS-936558 (MDX-1106)
ipilimumab YERVOY™
(Experimental)
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
nivolumab BMS-936558 (MDX-1106)
ipilimumab YERVOY™

Primary Outcomes

Measure
Safety and tolerability of Nivolumab plus Sunitinib, Pazopanib, or Ipilimumab measured by incidence of Adverse event (AE)
time frame: up to 100 days after last dose or longer
Safety and tolerability of Nivolumab plus Sunitinib, Pazopanib, or Ipilimumab measured by incidence of Serious adverse event (SAE)
time frame: up to 100 days after last dose or longer
Safety and tolerability of Nivolumab plus Sunitinib, Pazopanib, or Ipilimumab measured by incidence of lab abnormality
time frame: Within 28 days prior to first dose
Safety and tolerability of Nivolumab plus Sunitinib, Pazopanib, or Ipilimumab measured by incidence of lab abnormality
time frame: Day 1 of Cycles 1-4
Safety and tolerability of Nivolumab plus Sunitinib, Pazopanib, or Ipilimumab measured by incidence of lab abnormality
time frame: Day 8 of Cycles 1-4
Safety and tolerability of Nivolumab plus Sunitinib, Pazopanib, or Ipilimumab measured by incidence of lab abnormality
time frame: Day 22 of Cycles 1-4
Safety and tolerability of Nivolumab plus Sunitinib, Pazopanib, or Ipilimumab measured by incidence of lab abnormality
time frame: Day 29 of Cycles 1-4
Safety and tolerability of Nivolumab plus Sunitinib, Pazopanib, or Ipilimumab measured by incidence of lab abnormality
time frame: Day 1 of Cycles 5+
Safety and tolerability of Nivolumab plus Sunitinib, Pazopanib, or Ipilimumab measured by incidence of lab abnormality
time frame: Day 22 of Cycles 5+
Safety and tolerability of Nivolumab plus Sunitinib, Pazopanib, or Ipilimumab measured by incidence of lab abnormality
time frame: up to 100 days after last dose or longer

Secondary Outcomes

Measure
Antitumor activity of Nivolumab plus Sunitinib, Pazopanib, or Ipilimumab 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 Nivolumab plus Sunitinib, Pazopanib, or Ipilimumab 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

Eligibility Criteria

Male or female participants at least 18 years old.

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 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

Additional Information

Official title A Phase 1 Study of Nivolumab (BMS-936558) Plus Sunitinib, Pazopanib or Ipilimumab in Subjects With Metastatic Renal Cell Carcinoma
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Bristol-Myers Squibb.