Clinical trial NCT01668784: Study of Nivolumab (BMS-936558) vs. Everolimus in Pre-Treated Advanced or Metastatic Clear-cell Renal Cell Carcinoma (CheckMate 025)
Official title: A Randomized, Open-Label, Phase 3 Study of Nivolumab (BMS-936558) vs. Everolimus in Subjects With Advanced or Metastatic Clear-Cell Renal Cell Carcinoma Who Have Received Prior Anti-Angiogenic Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Advanced or Metastatic (Medically or Surgically Unresectable) Clear-cell Renal Cell Carcinoma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Ono Pharmaceutical Co. Ltd
First posted: 2012-08-20
Enrollment: 821
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to compare the clinical benefit, as measured by duration of overall survival, of Nivolumab vs. Everolimus in subjects with advanced or metastatic clear-cell renal cell carcinoma who have received prior anti-angiogenic therapy


Eligibility criteria: Inclusion Criteria:

* Men \& women ≥18 years of age
* Histologic confirmation of renal cell carcinoma (RCC) with clear-cell component
* Advanced/metastatic RCC
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
* Received 1 or 2 prior anti-angiogenic therapy regimens in advanced or metastatic setting
* No more than 3 total prior systemic treatment regimens in the advanced or metastatic setting, and evidence of progression on or after last treatment regimen received and within 6 months of enrollment
* Karnofsky Performance Score ≥70%

Exclusion Criteria:

* Any Central Nervous System (CNS) metastases or history of CNS metastases
* Prior therapy with an Mammalian target of rapamycin (mTOR) inhibitor
* Any active known or suspected autoimmune disease
* Uncontrolled adrenal insufficiency
* Active chronic liver disease
* Prior malignancy active within past 3 years, except for locally curable cancers

Other protocol-defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Overall Survival (OS) at Primary Endpoint
timeFrame: Randomization until 398 deaths, up to May 2015 (approximately 30 months)
Secondary outcomes:
measure: Investigator-assessed Objective Response Rate (ORR)
timeFrame: from randomization up to disease progression or death (approximately up to 105 Months)
measure: Investigator-assessed Duration of Objective Response
timeFrame: From randomization to date of disease progression or death or censoring if no progression or death occurred (approximately 105 months)
measure: Investigator-assessed Time to Objective Response
timeFrame: Randomization to date of first response (approximately 105 months)
measure: Investigator-assessed Time of Progression-free Survival (PFS)
timeFrame: from randomization up to disease progression or death (approximately up to 105 Months)
measure: Overall Survival (OS) by Programmed Death-Ligand 1 (PD-L1) Expression Level
timeFrame: Randomization to date of death or date of last contact for patients without documentation of death, up to May 2015 (approximately 30 months)
measure: Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events
timeFrame: Day of first dose to 30 days post study completion (approximately 106 months)
measure: Percentage of Participants With Disease-related Symptom Progression (DRSP)
timeFrame: from randomization up to disease progression or death (approximately up to 105 Months)
measure: Number of Participants Meeting Marked Laboratory Abnormality Criteria in Specific Liver and Thyroid Tests
timeFrame: Day 1 to 30 days post study completion (approximately 106 months)
measure: Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
timeFrame: Day 1 to 30 days post study completion (approximately 106 months)
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Local Institution - 0182
state: Arkansas
city: La Jolla
country: United States
facility: UCSD Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Local Institution - 0024
state: California
city: Los Angeles
country: United States
facility: University Of Southern California
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: San Francisco
country: United States
facility: Ucsf Helen Diller Family Comprehensive Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Institute
state: California
city: Aurora
country: United States
facility: University Of Colorado
state: Colorado
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Local Institution - 0027
state: District of Columbia
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute.
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Maywood
country: United States
facility: Loyola University Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
city: Iowa City
country: United States
facility: University Of Iowa Hospitals And Clinics
state: Iowa
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: Ann Arbor
country: United States
facility: University Of Michigan Comprehensive Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University Of South Carolina
state: South Carolina
city: Greenville
country: United States
facility: St Francis Hospital
state: South Carolina
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Ut Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Local Institution - 0139
state: Texas
city: San Antonio
country: United States
facility: CTRC at UTHSC San Antonio
state: Texas
city: Richmond
country: United States
facility: Local Institution - 0076
state: Virginia
city: Seattle
country: United States
facility: Local Institution - 0009
state: Washington
city: Seattle
country: United States
facility: University Of Washington
state: Washington
city: Berazategui
country: Argentina
facility: COIBA
state: Buenos Aires
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: San Miguel De Tucuman
country: Argentina
facility: Centro Para La Atencion Integral Del Paciente Oncologico
state: Tucuman
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Cordoba
country: Argentina
facility: Instituto Oncologico De Cordoba
city: Westmead
country: Australia
facility: Local Institution - 0095
state: New South Wales
city: Woodville South
country: Australia
facility: Local Institution
state: South Australia
city: Box Hill
country: Australia
facility: Local Institution
state: Victoria
city: Clayton
country: Australia
facility: Local Institution
state: Victoria
city: Melbourne
country: Australia
facility: Local Institution
state: Victoria
city: Linz
country: Austria
facility: Local Institution
city: Wien
country: Austria
facility: Local Institution
city: Wien
country: Austria
facility: Local Institution
city: Brussels
country: Belgium
facility: Local Institution
city: Bruxelles
country: Belgium
facility: Local Institution
city: Gent
country: Belgium
facility: Local Institution
city: Leuven
country: Belgium
facility: Local Institution
city: Ijui
country: Brazil
facility: Local Institution - 0125
state: RIO Grande DO SUL
city: Sao Paulo
country: Brazil
facility: Local Institution - 0124
city: Sao Paulo
country: Brazil
facility: Local Institution
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: Moncton
country: Canada
facility: Centre D'Oncologie Dr-Leon-Richard
state: New Brunswick
city: Halfax
country: Canada
facility: QEII Health Sciences Centre
state: Nova Scotia
city: Oshawa
country: Canada
facility: Local Institution - 0143
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Chum, Hopital Notre-Dame
state: Quebec
city: Montreal
country: Canada
facility: Local Institution - 0145
city: Hradec Kralove
country: Czechia
facility: Local Institution
city: Olomouc
country: Czechia
facility: Local Institution
city: Prague 5
country: Czechia
facility: Local Institution
city: Aarhus N
country: Denmark
facility: Local Institution
city: Herlev
country: Denmark
facility: Local Institution
city: Odense
country: Denmark
facility: Local Institution - 0137
city: Helsinki
country: Finland
facility: Local Institution
city: Vandoeuvre-lès-Nancy
country: France
facility: Local Institution - 0006
state: Lorraine
city: Bordeaux
country: France
facility: Local Institution - 0008
city: Bordeaux
country: France
facility: Local Institution
city: Lyon Cedex
country: France
facility: Local Institution - 0007
city: Lyon Cedex
country: France
facility: Local Institution
city: Marseille Cedex 9
country: France
facility: Local Institution - 0004
city: Marseille Cedex 9
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution - 0118
city: Poitiers
country: France
facility: Local Institution - 0003
city: Poitiers
country: France
facility: Local Institution
city: Saint Herblain Cedex
country: France
facility: Local Institution - 0005
city: Saint Herblain Cedex
country: France
facility: Local Institution
city: Toulouse Cedex 9
country: France
facility: Local Institution - 0012
city: Toulouse Cedex 9
country: France
facility: Local Institution
city: Vandoeuvre Les Nancy
country: France
facility: Local Institution
city: Villejuif Cedex
country: France
facility: Local Institution - 0002
city: Villejuif Cedex
country: France
facility: Local Institution
city: Aachen
country: Germany
facility: Local Institution
city: Dresden
country: Germany
facility: Local Institution
city: Erlangen
country: Germany
facility: Local Institution
city: Essen
country: Germany
facility: Local Institution
city: Hannover
country: Germany
facility: Local Institution
city: Heidelberg
country: Germany
facility: Local Institution - 0126
city: Munich
country: Germany
facility: Local Institution
city: Tuebingen
country: Germany
facility: Local Institution
city: Athens
country: Greece
facility: Alexandra General Hospital Of Athens
city: Thessaloniki
country: Greece
facility: Euromedica General Clinic of Thessaloniki
city: Tallaght
country: Ireland
facility: Local Institution
state: Dublin
city: Dublin
country: Ireland
facility: Local Institution - 0087
city: Dublin
country: Ireland
facility: Local Institution
city: Haifa
country: Israel
facility: Local Institution
city: Petah Tikva
country: Israel
facility: Local Institution - 0148
city: Ramat-gan
country: Israel
facility: Local Institution
city: Tel Aviv
country: Israel
facility: Local Institution
city: Arezzo
country: Italy
facility: Local Institution
city: Meldola (fc)
country: Italy
facility: Local Institution
city: Milano
country: Italy
facility: Local Institution - 0082
city: Rimini
country: Italy
facility: Local Institution
city: Roma
country: Italy
facility: Local Institution
city: Roma
country: Italy
facility: Local Institution
city: Rozzano
country: Italy
facility: Local Institution - 0102
city: Siena
country: Italy
facility: Local Institution
city: Terni
country: Italy
facility: Local Institution
city: Akita-shi
country: Japan
facility: Local Institution
state: Akita
city: Chiba-shi
country: Japan
facility: Local Institution
state: Chiba
city: Higashi-ku
country: Japan
facility: Local Institution
state: Fukuoka
city: Sapporo-city
country: Japan
facility: Local Institution
state: Hokkaido
city: Sapporo-shi
country: Japan
facility: Local Institution
state: Hokkaido
city: Morioka-shi
country: Japan
facility: Local Institution
state: Iwate
city: Yokohama
country: Japan
facility: Local Institution
state: Kanagawa
city: Kyoto-shi
country: Japan
facility: Local Institution
state: Kyoto
city: Osaka-sayama-shi
country: Japan
facility: Local Institution
state: Osaka
city: Suita
country: Japan
facility: Local Institution - 0169
state: Osaka
city: Hamamatsu-shi
country: Japan
facility: Local Institution - 0167
state: Shizuoka
city: Tokushima-shi
country: Japan
facility: Local Institution
state: Tokushima
city: Yamagata-shi
country: Japan
facility: Local Institution
state: Yamagata
city: Kobe-city, Hyogo
country: Japan
facility: Local Institution
city: Kumamoto
country: Japan
facility: Local Institution
city: Tokyo
country: Japan
facility: Local Institution
city: Tokyo
country: Japan
facility: Local Institution
city: Tokyo
country: Japan
facility: Local Institution
city: Tokyo
country: Japan
facility: Local Institution
city: Tokyo
country: Japan
facility: Local Institution
city: Tokyo
country: Japan
facility: Local Institution
city: Bergen
country: Norway
facility: Local Institution
city: Lorenskog
country: Norway
facility: Local Institution
city: Gdansk
country: Poland
facility: Local Institution
city: Lodz
country: Poland
facility: Local Institution
city: Poznan
country: Poland
facility: Local Institution
city: Rybnik
country: Poland
facility: Local Institution
city: Warszawa
country: Poland
facility: Local Institution
city: Wroclaw
country: Poland
facility: Local Institution
city: Bucharest
country: Romania
facility: Local Institution
city: Craiova
country: Romania
facility: Local Institution
city: Iasi
country: Romania
facility: Local Institution
city: Timisoara
country: Romania
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: St Petersburg
country: Russian Federation
facility: Local Institution
city: Pamplona
country: Spain
facility: Local Institution
state: Navarra
city: Barcelona
country: Spain
facility: Local Institution
city: Hospitalet De Llobregat
country: Spain
facility: Local Institution - 0064
city: Madrid
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Gothenberg
country: Sweden
facility: Local Institution
city: Solna
country: Sweden
facility: Local Institution
city: Cambridge
country: United Kingdom
facility: Local Institution
state: Cambridgeshire
city: Swansea
country: United Kingdom
facility: Local Institution - 0048
state: Carmarthenshire
city: Swansea
country: United Kingdom
facility: Local Institution
state: Carmarthenshire
city: London
country: United Kingdom
facility: Local Institution
state: Greater London
city: London
country: United Kingdom
facility: Local Institution
state: Greater London
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Klijn SL, Fenwick E, Kroep S, Johannesen K, Malcolm B, Kurt M, Kiff C, Borrill J. What Did Time Tell Us? A Comparison and Retrospective Validation of Different Survival Extrapolation Methods for Immuno-Oncologic Therapy in Advanced or Metastatic Renal Cell Carcinoma. Pharmacoeconomics. 2021 Mar;39(3):345-356. doi: 10.1007/s40273-020-00989-1. Epub 2021 Jan 11.
citation: Ambavane A, Yang S, Atkins MB, Rao S, Shah A, Regan MM, McDermott DF, Michaelson MD. Clinical and economic outcomes of treatment sequences for intermediate- to poor-risk advanced renal cell carcinoma. Immunotherapy. 2020 Jan;12(1):37-51. doi: 10.2217/imt-2019-0199. Epub 2020 Jan 29.
citation: Shah R, Botteman M, Solem CT, Luo L, Doan J, Cella D, Motzer RJ. A Quality-adjusted Time Without Symptoms or Toxicity (Q-TWiST) Analysis of Nivolumab Versus Everolimus in Advanced Renal Cell Carcinoma (aRCC). Clin Genitourin Cancer. 2019 Oct;17(5):356-365.e1. doi: 10.1016/j.clgc.2019.05.010. Epub 2019 May 31.
citation: Long GV, Tykodi SS, Schneider JG, Garbe C, Gravis G, Rashford M, Agrawal S, Grigoryeva E, Bello A, Roy A, Rollin L, Zhao X. Assessment of nivolumab exposure and clinical safety of 480 mg every 4 weeks flat-dosing schedule in patients with cancer. Ann Oncol. 2018 Nov 1;29(11):2208-2213. doi: 10.1093/annonc/mdy408.
citation: Escudier B, Motzer RJ, Sharma P, Wagstaff J, Plimack ER, Hammers HJ, Donskov F, Gurney H, Sosman JA, Zalewski PG, Harmenberg U, McDermott DF, Choueiri TK, Richardet M, Tomita Y, Ravaud A, Doan J, Zhao H, Hardy H, George S. Treatment Beyond Progression in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab in CheckMate 025. Eur Urol. 2017 Sep;72(3):368-376. doi: 10.1016/j.eururo.2017.03.037. Epub 2017 Apr 12.
citation: Escudier B, Sharma P, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, Castellano D, Gurney H, Donskov F, Peltola K, Wagstaff J, Gauler TC, Ueda T, Zhao H, Waxman IM, Motzer RJ; CheckMate 025 investigators. CheckMate 025 Randomized Phase 3 Study: Outcomes by Key Baseline Factors and Prior Therapy for Nivolumab Versus Everolimus in Advanced Renal Cell Carcinoma. Eur Urol. 2017 Dec;72(6):962-971. doi: 10.1016/j.eururo.2017.02.010. Epub 2017 Mar 3.
citation: Cella D, Grunwald V, Nathan P, Doan J, Dastani H, Taylor F, Bennett B, DeRosa M, Berry S, Broglio K, Berghorn E, Motzer RJ. Quality of life in patients with advanced renal cell carcinoma given nivolumab versus everolimus in CheckMate 025: a randomised, open-label, phase 3 trial. Lancet Oncol. 2016 Jul;17(7):994-1003. doi: 10.1016/S1470-2045(16)30125-5. Epub 2016 Jun 6.
citation: Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, Castellano D, Choueiri TK, Gurney H, Donskov F, Bono P, Wagstaff J, Gauler TC, Ueda T, Tomita Y, Schutz FA, Kollmannsberger C, Larkin J, Ravaud A, Simon JS, Xu LA, Waxman IM, Sharma P; CheckMate 025 Investigators. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015 Nov 5;373(19):1803-13. doi: 10.1056/NEJMoa1510665. Epub 2015 Sep 25.