The purpose of this study is to make a preliminary assessment of the efficacy of a combined APR-246 and carboplatin/PLD chemotherapy regimen, compared with carboplatin/PLD chemotherapy regimen alone, in patients with platinum sensitive recurrent high grade serous ovarian cancer (HGSOC) with mutated p53. In addition, the study aims to assess the safety profile of the combined APR-246 and carboplatin/PLD chemotherapy regimen compared with carboplatin/PLD chemotherapy regimen alone, to evaluate potential biomarkers, and to assess the biological activity in tumor and surrogate tissues. The trial will enroll up to a maximum of 400 patients.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
247
Intravenous infusion.
Intravenous infusion.
UCLA
Los Angeles, California, United States
University of Chicago
Chicago, Illinois, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States
Phase Ib: Dose-limiting Toxicities (DLT) (See Description) of Combined APR-246 and Carboplatin/PLD Regimen
DLT: Hematological and non-hematological toxicities according to grade/days stated in the protocol.
Time frame: Until the end of the first treatment cycle, i.e., Day 28
Phase Ib and II: Progression Free Survival (PFS)
Phase Ib: Progression-free Survival is calculated from date of enrollment to the date of disease progression or death due to any cause, whichever occurs first. Symptomatic deterioration is not considered PD. For a patient without evidence of disease progression or death, Progression-free survival will be censored at the date of last evaluable tumor assessment. Patients with no evaluable tumor assessments will be censored at the date of first study drug administration. Phase II: Progression-free survival (PFS) based on Blinded Independent Central Review (BICR) is the primary endpoint and is defined as the number of days from the date of randomization to the date of objective disease progression or relapse (according to RECIST v1.1 only) or death due to any cause, whichever occurs first. If neither event occurs, PFS is censored at the date of the last evaluable tumor assessment. Symptomatic deterioration is not considered objective disease progression.
Time frame: Up to 24 months
Phase Ib and Phase II: Overall Response Rate (RR)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: Up to 24 months
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Oregon Health & Science University
Portland, Oregon, United States
The University of Pennsylvania
Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
UPMC Hillman Cancer Center, Magee-Womens Hospital
Pittsburgh, Pennsylvania, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
...and 45 more locations