The purpose of this study is to evaluate the efficacy and safety of single-agent MLN0128 and the combination of MLN0128 + MLN1117 compared with everolimus in the treatment of participants with metastatic clear-cell renal cell carcinoma (mccRCC) that have progressed on vascular endothelial growth factor (VEGF)-targeted therapy.
The drugs being tested in this study are called MLN0128 and MLN1117. MLN0128 and MLN1117 are being tested to treat people who have mccRCC. This study will assess the efficacy and safety of MLN0128 and MLN1117 as well as how it is processed by the body in participants with advanced or mccRCC. The study will enroll approximately 96 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the three treatment groups: * Everolimus 10 mg once daily * MLN0128 30 mg once weekly * MLN0128 4 mg once daily for 3 days per week + MLN1117 200 mg once daily for 3 days per week All participants will be asked to take the study drug at the same time on each scheduled day. This multi-center trial will be conducted worldwide. The overall time to participate in this study is 2 years after last participant is randomized, or when the last participant discontinues study treatment (approximately 3 years). Participants will make multiple visits to the clinic including a follow-up visit 30 to 40 days after receiving their last dose of study drug or prior to start of subsequent anticancer therapy for safety assessment. Participants will then be followed for Progression Free and Overall Survival.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
96
Progression-Free Survival (PFS)
PFS was defined as the time from the date of randomization to the date of first documentation of progressive disease (PD) or death due to any cause, whichever occurs first. Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time frame: From first dose of study drug up to disease progression or death, assessed up to 43 months
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An AE was defined as any untoward medical occurrence in participants administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. TEAE was defined as the event that occur after administration of the first dose of study drug and through 30 days after the last dose of study drug.
Time frame: From first dose of study drug through 30 days after the last dose of study drug (approximately up to 31 months)
Overall Survival (OS)
Overall survival in months was defined as the time from the date of randomization to the date of death.
Time frame: From first dose of study drug through 30 days after the last dose of study drug (up to 51 months)
Time-to-progression (TTP)
TTP in months is defined as the time from the date of randomization to the date of first documentation of progression. Per RECIST v1.1, PD was defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
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USC Norris Comprehensive Cancer Center
Los Angeles, California, United States
Florida Cancer Specialists-Broadway
Venice, Florida, United States
Florida Cancer Specialists
West Palm Beach, Florida, United States
Hackensack University Medical Center PARTNER
Hackensack, New Jersey, United States
The Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital
Columbus, Ohio, United States
Tennessee Oncology
Nashville, Tennessee, United States
The Center for Cancer and Blood Disorders
Weatherford, Texas, United States
CancerCare Manitoba
Winnipeg, Manitoba, Canada
McMaster University
Hamilton, Ontario, Canada
Fakultni nemocnice u sv. Anny v Brne
Brno, Czechia
...and 26 more locations
Time frame: From first dose of study drug up to disease progression or death (up to 51 months)
Objective Response Rate (ORR)
ORR was defined as the percentage of participants among response evaluable analysis set who achieve a best overall response of complete response (CR) or partial response (PR) based on investigators assessment of response following RECIST 1.1. CR was defined as disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions.
Time frame: From first dose of study drug to disease progression or death (up to 51 months)
Clinical Benefit Rate (CBR)
CBR is defined as the percentage of participants who achieve a best response of CR, PR or stable disease (SD) of any duration. CR was defined as disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time frame: From first dose of study drug up to disease progression or death (up to 51 months)
CBR With SD Duration of at Least 16 Weeks
CBR with SD duration of at least 4 months (CBR-16) was defined as the percentage of participants who achieve CR or PR of any duration or have SD with duration of at least 16 weeks. CR was defined as disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time frame: Up to Week 16