NCT01668784 · CITED IN SOURCE DOCUMENTS

Study of Nivolumab (BMS-936558) vs. Everolimus in Pre-Treated Advanced or Metastatic Clear-cell Renal Cell Carcinoma (CheckMate 025)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2022-08-09

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

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Overall Survival (OS) at Primary Endpoint

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outcome · POSTED

Investigator-assessed Objective Response Rate (ORR)

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outcome · POSTED

Investigator-assessed Duration of Objective Response

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outcome · POSTED

Investigator-assessed Time to Objective Response

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outcome · POSTED

Investigator-assessed Time of Progression-free Survival (PFS)

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outcome · POSTED

Overall Survival (OS) by Programmed Death-Ligand 1 (PD-L1) Expression Level

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outcome · POSTED

Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events

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outcome · POSTED

Percentage of Participants With Disease-related Symptom Progression (DRSP)

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outcome · POSTED

Number of Participants Meeting Marked Laboratory Abnormality Criteria in Specific Liver and Thyroid Tests

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outcome · POSTED

Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units

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outcome · POSTED

Extended Collection to Post Hoc Overall Survival (OS)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Nivolumab 3 mg/kg solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
intervention Names
Biological: Nivolumab
label
Arm 1: Nivolumab
type
EXPERIMENTAL
description
Everolimus 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
intervention Names
Drug: Everolimus
label
Arm 2: Everolimus
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Arm 1: Nivolumab
name
Nivolumab
other Names
BMS-936558
type
BIOLOGICAL
arm Group Labels
Arm 2: Everolimus
name
Everolimus
other Names
Afinitor
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 821
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Overall Survival (OS) was defined as the time from randomization to the date of death. Participants that had not died were censored at last known date alive. Median OS time was calculated using Kaplan-Meier Estimates. Interim analysis for the Primary Endpoint occurred after 398 deaths (70% of the total OS events needed for final analysis). At that time the data monitoring committee noted that the pre-specified boundary for OS (nominal significance level p \< 0.0148) was crossed while no new safety signals that would affect continuation of the study were found. The study was stopped early by the Sponsor, Bristol-Myers Squibb (BMS) and the interim analysis became the final analysis. As a result, participants in the everolimus groups could be assessed for a crossover to nivolumab treatment if they met all inclusion criteria.
measure
Overall Survival (OS) at Primary Endpoint
time Frame
Randomization until 398 deaths, up to May 2015 (approximately 30 months)

secondary Outcomes

description
ORR is defined as Percentage of participants with a best response of complete response (CR) or partial response (PR) divided by number of randomized participants. 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, the baseline sum diameters used as reference. Tumor assessments began at 8 weeks following randomization and continued every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or death. CIs used Clopper and Pearson.
measure
Investigator-assessed Objective Response Rate (ORR)
time Frame
from randomization up to disease progression or death (approximately up to 105 Months)
description
Duration of objective response is defined as the time from study start date to response, CR or partial response, PR) to the date of the first documented tumor progression as determined by the investigator (per RECIST 1.1 criteria or clinical) or death due to any cause, whichever occurred first. For participants who neither progress nor die, the duration of objective response were censored at the same time they were censored for the primary definition. 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, the baseline sum diameters used as reference. Based on Kaplan-Meier Estimates.
measure
Investigator-assessed Duration of Objective Response
time Frame
From randomization to date of disease progression or death or censoring if no progression or death occurred (approximately 105 months)
description
Time to objective response is defined as the time from randomization to first response (complete response, CR or partial response, PR). 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, the baseline sum diameters used as reference.
measure
Investigator-assessed Time to Objective Response
time Frame
Randomization to date of first response (approximately 105 months)
description
PFS=time from randomization to date of first documented tumor progression as determined by investigator (per RECIST 1.1 criteria or clinical) or death due to any cause, whichever occurred first. Participants who die without a reported prior progression and without subsequent anti-cancer therapy were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the date they were randomized. Participants who received any subsequent anti-cancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to or on initiation date of the subsequent anti-cancer therapy. Progressive disease: \>=20% increase in sum of target lesion diameters and sum must show absolute increase of \>=5mm; smallest sum on study as reference. Based on Kaplan-Meier Estimates.
measure
Investigator-assessed Time of Progression-free Survival (PFS)
time Frame
from randomization up to disease progression or death (approximately up to 105 Months)
description
Quantifiable PD-L1 expression=percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per Dako PD-L1 IHC assay. If the PD-L1 staining could not be quantified it was classified as: indeterminate=tumor cell membrane staining hampered for reasons attributed to biology of tumor biopsy specimen and not due to improper sample preparation or handling; not evaluable=tumor biopsy specimen was not optimally collected or prepared. Not evaluable determined from H\&E process before the tumor biopsy specimen was sent for evaluation or from H\&E process during PD-L1 evaluation; baseline PD-L1 expression=if more than one tumor biopsy specimen was available, the most recently collected specimen with a quantifiable result. If all specimens for a given participant are either indeterminate or not evaluable, then the PD-L1 expression was considered indeterminate as long as at least one specimen is indeterminate. Otherwise, PD-L1 expression was considered not evaluable.
measure
Overall Survival (OS) by Programmed Death-Ligand 1 (PD-L1) Expression Level
time Frame
Randomization to date of death or date of last contact for patients without documentation of death, up to May 2015 (approximately 30 months)
description
Adverse event (AE) defined: any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Serious adverse event (SAE) defined: 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.
measure
Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events
time Frame
Day of first dose to 30 days post study completion (approximately 106 months)
description
Disease-related symptom progression rate (DRSPR)=a decrease of two points in the Functional Assessment of Cancer Therapy-Kidney Symptom Index - Disease Related Symptoms (FKSI-DRS) questionnaire relative to the participant's baseline FKSI-DRS score with no later increase above this threshold observed during the course of the study. The 9 items of the FKSI-DRS were summarized into a symptom scale ranging in score from 0 to 36, with 0 being the worst possible score and 36 being the best possible score. A single measure reporting a decrease of at least 2 units was considered disease-related symptom progression only if it was the last one available for the participant. In order to consider a questionnaire received as valid, over 50% of the items were to be completed. Calculated by the Clopper-Pearson method for each treatment group.
measure
Percentage of Participants With Disease-related Symptom Progression (DRSP)
time Frame
from randomization up to disease progression or death (approximately up to 105 Months)
description
Aspartate aminotransferase, AST. Alanine aminotransaminase, ALT. Total bilirubin, tBIL. Thyroid stimulating hormone, TSH. Upper limit of normal (ULN). Units per Liter (U/L). Results reported in International System of Units (SI).
measure
Number of Participants Meeting Marked Laboratory Abnormality Criteria in Specific Liver and Thyroid Tests
time Frame
Day 1 to 30 days post study completion (approximately 106 months)
description
Common Terminology Criteria (CTC) version 4.0 in International System of Units (SI); Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. Hematology parameters=Hemoglobin (Gr 3: \< 8.0 g/dL), Platelet Count (Gr 3: 25.0 -\< 50.0\*10\^9 c/L; Gr 4: \< 25.0\*10\^9 c/L), Leukocyte Count (Gr 3: 1.0 -\< 2.0\*10\^3 c/µL; Gr4: \< 1.0\*10\^3 c/µL), Absolute Lymphocyte Count (Gr 3: 0.2 -\< 0.5\*10\^3 c/µL; Gr 4: \< 0.2\*10\^3 c/µL), Absolute Neutrophil Count (Gr 3: 0.5 - \< 1.0\*10\^3 c/µL; Gr 4: \< 0.5\*10\^3 c/µL). Liver Function parameters=Alkaline Phosphatase (Gr 3: \> 5.0 - 20.0 U/L \* ULN; Gr 4: \> 20.0 U/L \* ULN), AST (Gr 3: \> 5.0 - 20.0 U/L \* ULN; Gr 4: \> 20.0 U/L \* ULN), ALT (Gr 3: \> 5.0 - 20.0 U/L \* ULN; Gr 4: \> 20.0 U/L \* ULN), tBIL (Gr 3: \> 3.0 - 10.0 mg/dL \* ULN; Gr 4: \> 10.0 mg/dL \* ULN). Renal parameter=Creatinine (Grade: Gr3: \> 3.0 - 6.0 mg/dL \*ULN; Gr4: \> 6.0 mg/dL \*ULN). Cells per microliter (c/µL). Cells per Liter (c/L). Grams per deciliter (g/dL). Milligrams per deciliter (mg/dL).
measure
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units
time Frame
Day 1 to 30 days post study completion (approximately 106 months)

Full study description

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

Source references

references

citation
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pmid
33428174
type
DERIVED
citation
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pmid
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citation
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pmid
31272883
type
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citation
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pmid
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type
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citation
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pmid
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type
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citation
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pmid
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type
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citation
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pmid
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type
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citation
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pmid
26406148
type
DERIVED