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

Renal Cell Carcinoma Clinical Trial

Official title:

A Phase 1 Study of Nivolumab (BMS-936558) Plus Sunitinib, Pazopanib or Ipilimumab in Subjects With Metastatic Renal Cell Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01472081
• Other study ID #: CA209-016
• Status: Completed
• Phase: Phase 1
• Start date: February 9, 2012
• Est. completion date: June 3, 2021

Study information

• Verified date: November 2021
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 194
• Est. completion date: June 3, 2021
• Est. primary completion date: February 2, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Clear-cell Metastatic Renal Cell Carcinoma
• Renal Cell Carcinoma

Intervention

Biological:
• Nivolumab

• Pazopanib

Drug:
• Sunitinib

Biological:
• Ipilimumab

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	BC Cancer Agency - Vancouver Centre	Vancouver	British Columbia
United States	Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Blumenthal Cancer Center	Charlotte	North Carolina
United States	Cleveland Clinic	Cleveland	Ohio
United States	City Of Hope	Duarte	California
United States	University Of Texas M.D. Anderson Cancer Center	Houston	Texas
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Memorial Sloan Kettering Nassau	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Ono Pharmaceutical Co. Ltd

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation	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.	From date of first dose to date of last dose plus 100 days (assessed up to March 2016, approximately 49 months)
Secondary	Best Overall Response Rate (BOR)	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.	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)
Secondary	Objective Response Rate (ORR)	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.	From date of first dose to interim analysis (Assessed up to March 2016, approximately 49 months)
Secondary	Duration of Response (DOR)	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).	From date of first dose to date of disease progression or death, whichever occurred first (assessed up to March 2016, approximately 49 months)
Secondary	Rate of Progression-free Survival (PFS) at Week 24	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.	24 weeks
Secondary	Progression-free Survival (PFS)	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.	From date of first dose to date of disease progression or death, whichever occurred first (assessed up to March 2016, approximately 49 months)

External Links

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