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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Ono Pharmaceutical Company, Ltd.
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01472081
First received: October 26, 2011
Last updated: April 8, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Renal Cell Carcinoma
Clear-cell Metastatic Renal Cell Carcinoma
Biological: Nivolumab
Biological: Pazopanib
Drug: Sunitinib
Biological: Ipilimumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of Nivolumab (BMS-936558) Plus Sunitinib, Pazopanib or Ipilimumab in Subjects With Metastatic Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of Nivolumab plus Sunitinib, Pazopanib, or Ipilimumab measured by incidence of lab abnormality [ Time Frame: Day 1 of Cycles 1-4 ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of Nivolumab plus Sunitinib, Pazopanib, or Ipilimumab measured by incidence of lab abnormality [ Time Frame: Day 8 of Cycles 1-4 ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of Nivolumab plus Sunitinib, Pazopanib, or Ipilimumab measured by incidence of lab abnormality [ Time Frame: Day 22 of Cycles 1-4 ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of Nivolumab plus Sunitinib, Pazopanib, or Ipilimumab measured by incidence of lab abnormality [ Time Frame: Day 29 of Cycles 1-4 ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of Nivolumab plus Sunitinib, Pazopanib, or Ipilimumab measured by incidence of lab abnormality [ Time Frame: Day 1 of Cycles 5+ ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of Nivolumab plus Sunitinib, Pazopanib, or Ipilimumab measured by incidence of lab abnormality [ Time Frame: Day 22 of Cycles 5+ ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 175
Study Start Date: February 2012
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Biological: Nivolumab
Other Name: BMS-936558 (MDX-1106)
Drug: Sunitinib
Other Names:
  • Sutent®
  • Sunitinib Malate
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

Biological: Nivolumab
Other Name: BMS-936558 (MDX-1106)
Biological: Pazopanib
Other Name: Votrient (Pazopanib hydrochloride)
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

Biological: Nivolumab
Other Name: BMS-936558 (MDX-1106)
Biological: Ipilimumab
Other Name: YERVOY™
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

Biological: Nivolumab
Other Name: BMS-936558 (MDX-1106)
Biological: Ipilimumab
Other Name: YERVOY™
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

Biological: Nivolumab
Other Name: BMS-936558 (MDX-1106)
Biological: Ipilimumab
Other Name: YERVOY™

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01472081

Locations
United States, California
City Of Hope
Duarte, California, United States, 91010-3000
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 11065
United States, North Carolina
Levine Cancer Institute
Charlotte, North Carolina, United States, 28204
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, Tennessee
Tennessee Oncology, Pllc
Nashville, Tennessee, United States, 37203
United States, Texas
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009
Canada, Alberta
Local Institution
Calgary, Alberta, Canada, T2N 4N2
Local Institution
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
Local Institution
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
Local Institution
Ottawa, Ontario, Canada, K1H 8L6
Local Institution
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Bristol-Myers Squibb
Ono Pharmaceutical Company, Ltd.
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01472081     History of Changes
Other Study ID Numbers: CA209-016
Study First Received: October 26, 2011
Last Updated: April 8, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Sunitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on April 16, 2014