The primary purpose of this study is to determine if sapanisertib in combination with weekly paclitaxel improves progression-free survival (PFS) compared to weekly paclitaxel alone.
The drugs being evaluated in this study are sapanisertib and MLN1117. Sapanisertib is being evaluated as a single agent and in combination with paclitaxel or MLN1117 to treat women with advanced, recurrent, or persistent endometrial cancer. This study will evaluate the efficacy and safety of each drug or drug combination. The study will enroll approximately 241 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of 4 treatment groups: * Paclitaxel 80 mg/m\^2 * Paclitaxel 80 mg/m\^2 + Sapanisertib 4 mg * Sapanisertib 30 mg * Sapanisertib 4 mg + MLN1117 200 mg Participants will receive either paclitaxel intravenous (IV) weekly, Paclitaxel IV along with sapanisertib orally, sapanisertib orally, or sapanisertib and MLN1117 orally. This is a multicenter, multinational trial. Participants will make multiple visits to the clinic, with an end of treatment visit (EOT) which will occur 30 to 40 days after receiving their last dose of study drug or before the start of any subsequent anticancer therapy. After EOT, participants will be followed for PFS and overall survival (OS).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
241
Paclitaxel intravenous solution.
Sapanisertib capsules.
MLN1117 capsules.
Progression Free Survival (PFS)
PFS is defined as the time in months 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 RECIST v1.1, 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: Up to approximately 30 months
Number of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE)
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: From the first dose of study drug through 30 days after the last dose of study drug (Up to approximately 54 months)
Overall Survival (OS)
OS is defined as the time in months from the date of randomization to the date of death.
Time frame: Up to approximately 54 months
Time to Tumor Progression (TTP)
TTP is defined as the time in months from the date of randomization to the date of first documentation of progression. Per RECIST 1.1, 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: Up to 30 months
Overall Response Rate (ORR)
ORR is defined as the percentage of participants who achieved a best response of a complete response (CR) or partial response (PR). Per RECIST v1.1, 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.
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University of Alabama Comprehensive Cancer Center
Birmingham, Alabama, United States
University of Arizona Cancer Center
Phoenix, Arizona, United States
Marin Cancer Care
Greenbrae, California, United States
University of California San Diego Medical Center
La Jolla, California, United States
University of California at San Francisco (PARENT)
San Francisco, California, United States
Stanford School of Medicine
Stanford, California, United States
H. Lee Moffitt Cancer Center and Research Institute, Inc
Tampa, Florida, United States
Florida Cancer Specialists
West Palm Beach, Florida, United States
Augusta University
Augusta, Georgia, United States
Franciscan St. Francis Health
Indianapolis, Indiana, United States
...and 68 more locations
Time frame: Up to 30 months
Clinical Benefit Rate (CBR)
CBR is defined as the percentage of participants with CR or PR or SD (SD of any duration). Per RECIST v1.1, CR was defined as disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR is 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. 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: Up to 30 months
Clinical Benefit Rate (CBR) at Week 16 (CBR-16)
CBR-16 is defined as the percentage of participants who achieved CR or PR of any duration or have SD with a duration of at least 16 weeks. Per RECIST v1.1, 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. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. 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: Week 16