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

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ClinicalTrials.gov Identifier: NCT01472081
Recruitment Status : Active, not recruiting
First Posted : November 16, 2011
Results First Posted : August 2, 2019
Last Update Posted : October 29, 2019
Sponsor:
Collaborator:
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
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.

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 194 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Actual Study Start Date : January 25, 2012
Actual Primary Completion Date : February 2, 2016
Estimated Study Completion Date : June 30, 2021


Arm Intervention/treatment
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™




Primary Outcome Measures :
  1. Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation [ Time Frame: 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 :
  1. Best Overall Response Rate (BOR) [ Time Frame: 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.


  2. Objective Response Rate (ORR) [ Time Frame: 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.


  3. Duration of Response (DOR) [ Time Frame: 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).

  4. Rate of Progression-free Survival (PFS) at Week 24 [ Time Frame: 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.

  5. Progression-free Survival (PFS) [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01472081


Locations
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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, 21287
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, 10065
United States, North Carolina
Blumenthal Cancer Center
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
University Of Texas M.D. Anderson Cancer Center
Houston, Texas, United States, 77030-4009
Canada, Alberta
Tom Baker Cancer Centre
Calgary, Alberta, Canada, T2N 4N2
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
BC Cancer Agency - Vancouver Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 1Z5
Sponsors and Collaborators
Bristol-Myers Squibb
Ono Pharmaceutical Co. Ltd
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01472081     History of Changes
Other Study ID Numbers: CA209-016
First Posted: November 16, 2011    Key Record Dates
Results First Posted: August 2, 2019
Last Update Posted: October 29, 2019
Last Verified: October 2019
Additional relevant MeSH terms:
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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
Nivolumab
Ipilimumab
Sunitinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action