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

NCT ID: NCT01472081

Last Updated: 2021-12-02

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

194 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-02-09

Study Completion Date

2021-06-03

Brief Summary

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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

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Conditions

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Renal Cell Carcinoma Clear-cell Metastatic Renal Cell Carcinoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Sunitinib

Intervention Type DRUG

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Pazopanib

Intervention Type BIOLOGICAL

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Ipilimumab

Intervention Type BIOLOGICAL

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Ipilimumab

Intervention Type BIOLOGICAL

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Ipilimumab

Intervention Type BIOLOGICAL

Interventions

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Nivolumab

Intervention Type BIOLOGICAL

Pazopanib

Intervention Type BIOLOGICAL

Sunitinib

Intervention Type DRUG

Ipilimumab

Intervention Type BIOLOGICAL

Other Intervention Names

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BMS-936558 (MDX-1106) Votrient (Pazopanib hydrochloride) Sutent® Sunitinib Malate YERVOY™

Eligibility Criteria

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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)


* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ono Pharmaceutical Co. Ltd

INDUSTRY

Sponsor Role collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

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City Of Hope

Duarte, California, United States

Site Status

Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins

Baltimore, Maryland, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Memorial Sloan Kettering Nassau

New York, New York, United States

Site Status

Blumenthal Cancer Center

Charlotte, North Carolina, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Site Status

University Of Texas M.D. Anderson Cancer Center

Houston, Texas, United States

Site Status

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Site Status

Cross Cancer Institute

Edmonton, Alberta, Canada

Site Status

BC Cancer Agency - Vancouver Centre

Vancouver, British Columbia, Canada

Site Status

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

References

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Amin A, Plimack ER, Ernstoff MS, Lewis LD, Bauer TM, McDermott DF, Carducci M, Kollmannsberger C, Rini BI, Heng DYC, Knox J, Voss MH, Spratlin J, Berghorn E, Yang L, Hammers HJ. Safety and efficacy of nivolumab in combination with sunitinib or pazopanib in advanced or metastatic renal cell carcinoma: the CheckMate 016 study. J Immunother Cancer. 2018 Oct 22;6(1):109. doi: 10.1186/s40425-018-0420-0.

Reference Type DERIVED
PMID: 30348216 (View on PubMed)

Dorff TB, Pal SK, Quinn DI. Novel tyrosine kinase inhibitors for renal cell carcinoma. Expert Rev Clin Pharmacol. 2014 Jan;7(1):67-73. doi: 10.1586/17512433.2014.862496. Epub 2013 Dec 2.

Reference Type DERIVED
PMID: 24308791 (View on PubMed)

Related Links

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Other Identifiers

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CA209-016

Identifier Type: -

Identifier Source: org_study_id