Clinical Trial: Testing Olaparib and Temozolomide Versus the Usual Treatment for Uterine Leiomyosarcoma After Chemotherapy Has Stopped Working
Study Status: RECRUITING
Recruit Status: RECRUITING
Study Type: INTERVENTIONAL
Official Title: A Randomized Phase 2/3 Study of Olaparib Plus Temozolomide Versus Investigator's Choice for the Treatment of Patients With Advanced Uterine Leiomyosarcoma After Progression on Prior Chemothe
Brief Summary: This phase II/III trial compares the effect of the combination treatment with olaparib and temozolomide to trabectedin or pazopanib (two of the most common chemotherapy drugs used as usual approach) in patients with uterine leiomyosarcoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) after initial chemotherapy has stopped working.
The usual approach is defined as care most people get for advanced uterine leiomyosarcoma.
Olaparib is a PARP inhibitor.
PARP is a protein that helps repair damaged deoxyribonucleic acid (DNA).
Blocking PARP may prevent tumor cells from repairing their damaged DNA, causing them to die.
PARP inhibitors are a type of targeted therapy.
Temozolomide is in a class of medications called alkylating agents.
It works by slowing or stopping the growth of tumor cells in the body.
The combination of olaparib and temozolomide may work better than the usual treatment in shrinking or stabilizing advanced uterine leiomyosarcoma after initial chemotherapy has stopped working.
Detailed Summary:
PRIMARY OBJECTIVES:
I. To compare the progression free survival (PFS) of olaparib plus temozolomide (Arm 1) as compared to investigator's choice (trabectedin or pazopanib hydrochloride [pazopanib]) (Arm 2) for the treatment of patients with advanced uterine leiomyosarcoma (uLMS) who have received two or more prior lines of therapy as determined by investigator (local site) assessment.
(Phase 2) II.
To compare the overall survival (OS) of olaparib plus temozolomide (Arm 1) as compared to investigator's choice (trabectedin or pazopanib) (Arm 2) for the treatment of patients with advanced uLMS who have received two or more prior lines of therapy.
(Phase 3)
SECONDARY OBJECTIVES:
I. To evaluate the safety and tolerability of each treatment by determining adverse events using Common Terminology Criteria for Adverse Events (CTCAE) version 5 and patient-reported toxicity using Patient-Reported Outcome (PRO)-CTCAE version 1 in and across each treatment arm.
(Phase 2/3) II.
To evaluate the objective response rate (ORR), duration of response (DOR) and disease control rate (DCR) in and across each treatment arm as determined by investigator assessment.
(Phase 2/3)
EXPLORATORY OBJECTIVE:
I. To collect results of tumor genomic testing previously conducted as part of clinical care (when available) and (a) to determine the proportion of patients with a genomic alteration in a homologous recombination (HR) pathway gene and (b) to evaluate for any relationship between the presence of such an alteration and clinical benefit from olaparib and temozolomide.
(Phase 2/3)
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM 1: Patients receive temozolomide orally (PO) once daily (QD) on days 1-7 of each cycle and olaparib PO twice daily (BID) on days 1-7 of each cycle.
Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients undergo computed tomography (CT) scan and may undergo magnetic resonance imaging (MRI), bone scans, and collection of blood samples throughout the study.
ARM 2: Patients receive trabectedin intravenously (IV) continuously over 24 hours on day 1 of each cycle or pazopanib PO QD on days 1-21 of each cycle.
Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients undergo CT scan and may undergo MRI, bone scans, and collection of blood samples throughout the study.
After completion of study treatment, patients without disease progression are followed every 6 weeks until disease progression.
After disease progression, patients are followed every 3 months for the first 2 years, then every 6 months thereafter until 5 years post-randomization or death, whichever comes first.
Sponsor: National Cancer Institute (NCI)
Current Primary Outcome: Will be estimated using the Kaplan-Meier method, where the stratified log-rank test will be used to compare the distributions across the treatment arms.
PFS rates at 1 year, 2 years, and 5 years will also be reported, along with 95% confidence intervals.
Univariable and multivariable Cox models stratified by the stratification factors used in the randomization will be assessed as well.
Original Primary Outcome: Will be estimated using the Kaplan-Meier method, where the stratified log-rank test will be used to compare the distributions across the treatment arms.
PFS rates at 1 year, 2 years, and 5 years will also be reported, along with 95% confidence intervals.
Univariable and multivariable Cox models stratified by the stratification factors used in the randomization will be assessed as well.
Current Secondary Outcome:
Original Secondary Outcome:
Information By: National Cancer Institute (NCI)
Dates:
Date Received: June 22, 2022
Date Started: March 30, 2023
Date Completion: March 30, 2023
Last Updated: December 22, 2023
Last Verified: December 01, 2023
