Clinical trial NCT01472081: Nivolumab (BMS-936558; MDX-1106) in Combination With Sunitinib, Pazopanib, or Ipilimumab in Subjects With Metastatic Renal Cell Carcinoma (RCC) (CheckMate 016)
Official title: A Phase 1 Study of Nivolumab (BMS-936558) Plus Sunitinib, Pazopanib or Ipilimumab in Subjects With Metastatic Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Cell Carcinoma
Clear-cell Metastatic Renal Cell Carcinoma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Ono Pharmaceutical Co. Ltd
First posted: 2011-11-16
Enrollment: 194
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation
timeFrame: From date of first dose to date of last dose plus 100 days (assessed up to March 2016, approximately 49 months)
Secondary outcomes:
measure: Best Overall Response Rate (BOR)
timeFrame: 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)
measure: Objective Response Rate (ORR)
timeFrame: From date of first dose to interim analysis (Assessed up to March 2016, approximately 49 months)
measure: Duration of Response (DOR)
timeFrame: From date of first dose to date of disease progression or death, whichever occurred first (assessed up to March 2016, approximately 49 months)
measure: Rate of Progression-free Survival (PFS) at Week 24
timeFrame: 24 weeks
measure: Progression-free Survival (PFS)
timeFrame: From date of first dose to date of disease progression or death, whichever occurred first (assessed up to March 2016, approximately 49 months)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City Of Hope
state: California
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
city: Charlotte
country: United States
facility: Blumenthal Cancer Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Houston
country: United States
facility: University Of Texas M.D. Anderson Cancer Center
state: Texas
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: BC Cancer Agency - Vancouver Centre
state: British Columbia
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.