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RecruitingNCT05554328

Testing the Use of the Combination of Selumetinib and Olaparib or Selumetinib Alone Targeted Treatment for RAS Pathway Mutant Recurrent or Persistent Ovarian and Endometrial Cancers, A ComboMATCH Treatment Trial

A Randomized Trial of Selumetinib and Olaparib or Selumetinib Alone in Patients With Recurrent or Persistent RAS Pathway Mutant Ovarian and Endometrial Cancers: A ComboMATCH Treatment Trial

Status
Recruiting
Phase
Phase 2
Study type
Interventional
Enrollment
165 (estimated)
Sponsor
National Cancer Institute (NCI) · NIH
Sex
Female
Age
18 Years
Healthy volunteers
Not accepted

Summary

This phase II ComboMATCH treatment trial compares selumetinib plus olaparib to selumetinib alone in women with endometrial or ovarian (fallopian tube and primary peritoneal) cancer that has come back (recurrent) or that remains despite treatment (persistent) and harbors a mutation in the RAS pathway. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Olaparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep tumor cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. The addition of olaparib to selumetinib could increase the percentage of tumors that shrink as well as lengthen the time that the tumors remain stable (without progression) as compared to selumetinib alone.

Detailed description

PRIMARY OBJECTIVES: I. Compare progression free survival of combination of olaparib and selumetinib sulfate (selumetinib) to selumetinib alone in patients with RAS mutant ovarian cancer. (Cohort 1) II. Compare progression free survival of combination of olaparib and selumetinib to selumetinib alone in patients with RAS mutant endometrial cancer. (Cohort 2) SECONDARY OBJECTIVES: I. Determine safety of both arms per Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. II. Compare objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 between the two arms. III. Determine rate of objective response per RECIST 1.1 in those patients that crossover from the single agent arm to the combination arm. IV. Report duration of response of the two treatment arms. V. Collect tissue and provide it to the ComboMATCH Registration protocol to assess concordance between the diagnostic tumor mutation profile generated by the designated laboratories, the pre-treatment biopsy mutation profile, and the pre-treatment circulating tumor (ct)DNA mutation profile from plasma, as described in ComboMATCH Registration protocol. For this treatment substudy, the outcome objective will be to report the proportion of cases providing sufficient tissue for that integrated scientific activity in the ComboMATCH Registration protocol. TRANSLATIONAL OBJECTIVE: I. To assess association of baseline genomic and transcriptomic status with response and resistance to therapy. OUTLINE: Patients in both cohorts are randomized to 1 of 2 arms. ARM I: Patients receive selumetinib orally (PO) twice daily (BID) and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as echocardiogram (ECHO) or multigated acquisition (MUGA), and computed tomography (CT) scans throughout the trial. Patients may undergo bone marrow aspiration or biopsy as clinically indicated. ARM II: Patients receive selumetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience progression may elect to cross over to Arm I provided they have not had dose limiting toxicities to monotherapy selumetinib. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as ECHO or MUGA, and CT scans throughout the trial. Patients may undergo bone marrow aspiration or biopsy as clinically indicated. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Conditions

Interventions

TypeNameDescription
PROCEDUREBiopsy ProcedureUndergo tumor biopsy
PROCEDUREBiospecimen CollectionUndergo blood collection
PROCEDUREBone Marrow Aspiration and BiopsyUndergo bone marrow aspiration or biopsy
PROCEDUREComputed TomographyUndergo CT scan
PROCEDUREEchocardiography TestUndergo ECHO
PROCEDUREMultigated Acquisition ScanUndergo MUGA
DRUGOlaparibGiven PO
DRUGSelumetinib SulfateGiven PO

Timeline

Start date
2023-04-25
Primary completion
2028-10-01
Completion
2028-10-01
First posted
2022-09-26
Last updated
2026-04-13

Locations

296 sites across 2 countries: United States, Puerto Rico

Regulatory

Source: ClinicalTrials.gov record NCT05554328. Inclusion in this directory is not an endorsement.