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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01668784




Registration number
NCT01668784
Ethics application status
Date submitted
16/08/2012
Date registered
20/08/2012
Date last updated
9/08/2022

Titles & IDs
Public title
Study of Nivolumab (BMS-936558) vs. Everolimus in Pre-Treated Advanced or Metastatic Clear-cell Renal Cell Carcinoma (CheckMate 025)
Scientific 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
Secondary ID [1] 0 0
2011-005132-26
Secondary ID [2] 0 0
CA209-025
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced or Metastatic (Medically or Surgically Unresectable) Clear-cell Renal Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Experimental: Arm 1: Nivolumab - Nivolumab 3 mg/kg solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Active comparator: Arm 2: Everolimus - Everolimus 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS) at Primary Endpoint
Timepoint [1] 0 0
Randomization until 398 deaths, up to May 2015 (approximately 30 months)
Secondary outcome [1] 0 0
Investigator-assessed Objective Response Rate (ORR)
Timepoint [1] 0 0
from randomization up to disease progression or death (approximately up to 105 Months)
Secondary outcome [2] 0 0
Investigator-assessed Duration of Objective Response
Timepoint [2] 0 0
From randomization to date of disease progression or death or censoring if no progression or death occurred (approximately 105 months)
Secondary outcome [3] 0 0
Investigator-assessed Time to Objective Response
Timepoint [3] 0 0
Randomization to date of first response (approximately 105 months)
Secondary outcome [4] 0 0
Investigator-assessed Time of Progression-free Survival (PFS)
Timepoint [4] 0 0
from randomization up to disease progression or death (approximately up to 105 Months)
Secondary outcome [5] 0 0
Overall Survival (OS) by Programmed Death-Ligand 1 (PD-L1) Expression Level
Timepoint [5] 0 0
Randomization to date of death or date of last contact for patients without documentation of death, up to May 2015 (approximately 30 months)
Secondary outcome [6] 0 0
Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events
Timepoint [6] 0 0
Day of first dose to 30 days post study completion (approximately 106 months)
Secondary outcome [7] 0 0
Percentage of Participants With Disease-related Symptom Progression (DRSP)
Timepoint [7] 0 0
from randomization up to disease progression or death (approximately up to 105 Months)
Secondary outcome [8] 0 0
Number of Participants Meeting Marked Laboratory Abnormality Criteria in Specific Liver and Thyroid Tests
Timepoint [8] 0 0
Day 1 to 30 days post study completion (approximately 106 months)
Secondary outcome [9] 0 0
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
Timepoint [9] 0 0
Day 1 to 30 days post study completion (approximately 106 months)

Eligibility
Key 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%
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/10/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/07/2021
Sample size
Target
Accrual to date
Final
821
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Local Institution - 0095 - Westmead
Recruitment hospital [2] 0 0
Local Institution - Woodville South
Recruitment hospital [3] 0 0
Local Institution - Box Hill
Recruitment hospital [4] 0 0
Local Institution - Clayton
Recruitment hospital [5] 0 0
Local Institution - Melbourne
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
5011 - Woodville South
Recruitment postcode(s) [3] 0 0
3128 - Box Hill
Recruitment postcode(s) [4] 0 0
3168 - Clayton
Recruitment postcode(s) [5] 0 0
3000 - Melbourne
Recruitment outside Australia
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United States of America
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Arkansas
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Arezzo
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Kobe-city, Hyogo
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Bergen
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Rybnik
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Wroclaw
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Bucharest
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Craiova
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Iasi
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Timisoara
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Moscow
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Navarra
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Barcelona
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Hospitalet De Llobregat
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Madrid
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Sweden
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Gothenberg
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Sweden
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Solna
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United Kingdom
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Cambridgeshire
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United Kingdom
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Carmarthenshire
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United Kingdom
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Greater London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bristol-Myers Squibb
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Ono Pharmaceutical Co. Ltd
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/study/NCT01668784
Trial related presentations / publications
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.
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.
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.
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.
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.
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. Erratum In: Eur Urol. 2018 Apr;73(4):e116-e118. doi: 10.1016/j.eururo.2017.12.016.
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. Erratum In: Lancet Oncol. 2016 Jul;17(7):e270. doi: 10.1016/S1470-2045(16)30232-7.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01668784