Testing the Addition of an Immunotherapy Drug, Tremelimumab, to the PARP Inhibition Drug, Olaparib, for Recurrent Ovarian, Fallopian Tube or Peritoneal Cancer

Recurrent Fallopian Tube Carcinoma Clinical Trial

Official title: A Phase II Randomized Trial of Olaparib Versus Olaparib Plus Tremelimumab in Platinum-Sensitive Recurrent Ovarian Cancer

Status Active, not recruiting

Clinical Trial Summary

This phase II trial studies how well olaparib with or without tremelimumab works in treating patients with ovarian, fallopian tube, or peritoneal cancer that has come back (recurrent). PARPs are proteins that help repair deoxyribonucleic acid (DNA) mutations. PARP inhibitors, such as olaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Immunotherapy with monoclonal antibodies, such as tremelimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving olaparib and tremelimumab together may work better than olaparib alone in treating patients with ovarian, fallopian tube, or peritoneal cancer.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine whether olaparib plus tremelimumab has adequate safety in the study population. (Safety Lead-in Trial Components) II. To compare the progression-free survival (PFS) duration of olaparib monotherapy versus olaparib plus tremelimumab in women with recurrent, platinum sensitive ovarian, primary peritoneal, or fallopian tube cancer. (Phase II Trial Component)

SECONDARY OBJECTIVES:

I. To compare the overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in women with recurrent, platinum sensitive ovarian, primary peritoneal or fallopian tube cancer treated with either olaparib monotherapy or olaparib plus tremelimumab.

II. To compare the overall survival (OS) of women with recurrent, platinum sensitive ovarian, primary peritoneal or fallopian tube cancer treated with either olaparib monotherapy or olaparib plus tremelimumab.

EXPLORATORY OBJECTIVES:

I. To explore whether conditions in the tumor microenvironment (as measured by gene expression signature in archived tumor samples) identify patients that benefit from combined olaparib and tremelimumab immunotherapy.

II. To explore whether mutations in BRCA1/2 genes or other evidence of homologous repair deficiency (HRD+) is prognostic and/or predictive of response to combined olaparib and tremelimumab immunotherapy.

III. To explore associations between PD1 expression in the tumor microenvironment and outcome and changes in circulating leukocyte populations.

IV. To explore the correlation between tumor mutational burden and response to olaparib and tremelimumab immunotherapy.

V. To explore the impact of olaparib and tremelimumab versus olaparib monotherapy on circulating leukocyte subsets via exploration of the immunomodulatory effects of PARP inhibition and the added impact of CTLA4 blockade in this patient population.

VI. To explore cytokine/chemokine levels using a multiplex immunoassay (Olink) and correlate these levels with clinical endpoints.

VII. To use cell-free deoxyribonucleic acid (DNA) to assess BRCA mutation status as a mechanism of acquired resistance to prior PARP inhibition and to compare with treatment efficacy.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive olaparib orally (PO) twice daily (BID) in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) as well as blood sample collection throughout the trial.

ARM II: Patients receive olaparib as in Arm I. Patients also receive tremelimumab intravenously (IV) over 60 minutes on day 1. Cycles of tremelimumab repeat every 4 weeks for 4 doses and then every 12 weeks for up to 2 years total in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI as well as blood sample collection throughout the trial.

After completion of study treatment, patients are followed up monthly for 3 months, then every 3 months for 2 years, followed by every 6 months for 3 years. ;

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma
• Carcinoma, Endometrioid
• Fallopian Tube Endometrioid Tumor
• Fallopian Tube Neoplasms
• Hypersensitivity
• Malignant Ovarian Endometrioid Tumor
• Platinum-Sensitive Fallopian Tube Carcinoma
• Platinum-Sensitive Ovarian Carcinoma
• Platinum-Sensitive Primary Peritoneal Carcinoma
• Primary Peritoneal High Grade Serous Adenocarcinoma
• Recurrence
• Recurrent Fallopian Tube Carcinoma
• Recurrent Fallopian Tube Endometrioid Adenocarcinoma
• Recurrent Ovarian Endometrioid Adenocarcinoma
• Recurrent Ovarian Serous Adenocarcinoma
• Recurrent Primary Peritoneal Carcinoma
• Recurrent Primary Peritoneal Endometrioid Adenocarcinoma

• NCT number: NCT04034927
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 4, 2019
• Completion date: September 21, 2024