Comparison of Standard of Care Treatment With a Triplet Combination of Targeted Immunotherapeutic Agents

Ovarian Seromucinous Carcinoma Clinical Trial

Official title: A Randomized Phase II Trial of Triplet Therapy (A PD-L1 Inhibitor Durvalumab (MEDI4736) in Combination With Olaparib and Cediranib) Compared to Olaparib and Cediranib or Durvalumab (MEDI4736) and Cediranib or Standard of Care Chemotherapy in Women With Platinum-Resistant Recurrent Epithelial Ovarian Cancer, Primary Peritoneal or Fallopian Cancer Who Have Received Prior Bevacizumab

Status Active, not recruiting

Clinical Trial Summary

This phase II trial studies the possible benefits of treatment with different combinations of the drugs durvalumab, olaparib and cediranib vs. the usual treatment in patients with ovarian, primary peritoneal, or fallopian tube cancer that has come back after a period of improvement with platinum therapy (recurrent platinum resistant). Usual treatment is the type of treatment most patients with this condition receive if they are not part of a clinical study. Combination therapies studied in this trial include MEDI4736 (durvalumab) plus olaparib and cediranib, durvalumab and cediranib, or olaparib and cediranib. Monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumors cells to grow and spread. Olaparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Cediranib may stop the growth of tumor cells by blocking VEGF (an enzyme). needed for cell growth. Giving different combinations of durvalumab, olaparib and cediranib may work better in increasing the duration of time that the cancer does not progress compared to the usual treatment.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To assess the efficacy of the combinations durvalumab (MEDI4736) plus olaparib and cediranib, durvalumab (MEDI4736) plus cediranib, or olaparib and cediranib, as measured by progression-free survival (PFS), as compared to physician's choice standard of care chemotherapy, in patients with recurrent platinum-resistant ovarian, primary peritoneal or fallopian tube cancer who had prior bevacizumab.

SECONDARY OBJECTIVES:

I. To assess the efficacy of the combinations durvalumab (MEDI4736) plus olaparib and cediranib, durvalumab (MEDI4736) plus cediranib, or olaparib and cediranib, as measured by overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as compared to physician's choice standard of care chemotherapy, in patients with recurrent platinum-resistant ovarian, primary peritoneal or fallopian tube cancer who had prior bevacizumab.

II. To assess the efficacy of the combinations durvalumab (MEDI4736) plus olaparib and cediranib, durvalumab (MEDI4736) plus cediranib, or olaparib and cediranib, as measured by overall survival (OS), as compared to physician's choice standard of care chemotherapy, in patients with recurrent platinum-resistant ovarian, primary peritoneal or fallopian tube cancer who had prior bevacizumab.

OUTLINE: Patients are randomized to 1 of 4 arms.

ARM I: Patients receive paclitaxel intravenously (IV) over 60 minutes on days 1, 8, and 15, or pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1, or topotecan hydrochloride IV over 30 minutes on days 1, 8 and 15 or days 1-5 per the discretion of the treating physician. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening and as clinically indicated on study. Patients also undergo collection of blood and computed tomography (CT) with contrast during screening, and CT or magnetic resonance imaging (MRI) scans throughout the trial.

ARM II: Patients receive durvalumab IV over 60 minutes on day 1, cediranib maleate orally (PO) once daily (QD) Monday through Friday, and olaparib PO twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.

ARM III: Patients receive durvalumab IV over 60 minutes on day 1 and cediranib maleate PO QD Monday through Friday. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.

ARM IV: Patients receive cediranib maleate PO QD on days 1-28 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.

After completion of study treatment, patients are followed up periodically for up to 5 years. ;

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma, Mucinous
• Carcinoma
• Carcinoma, Endometrioid
• Carcinoma, Ovarian Epithelial
• Carcinoma, Transitional Cell
• Cystadenocarcinoma
• Fallopian Tube Mucinous Adenocarcinoma
• Fallopian Tube Neoplasms
• Ovarian Neoplasms
• Ovarian Seromucinous Carcinoma
• Platinum-Refractory Fallopian Tube Carcinoma
• Platinum-Refractory Ovarian Carcinoma
• Platinum-Refractory Primary Peritoneal Carcinoma
• Recurrence
• Recurrent Fallopian Tube Clear Cell Adenocarcinoma
• Recurrent Fallopian Tube Endometrioid Adenocarcinoma
• Recurrent Fallopian Tube Mucinous Adenocarcinoma
• Recurrent Fallopian Tube Transitional Cell Carcinoma
• Recurrent Fallopian Tube Undifferentiated Carcinoma
• Recurrent Low Grade Fallopian Tube Serous Adenocarcinoma
• Recurrent Ovarian Clear Cell Adenocarcinoma
• Recurrent Ovarian Endometrioid Adenocarcinoma
• Recurrent Ovarian Mucinous Adenocarcinoma
• Recurrent Ovarian Seromucinous Carcinoma
• Recurrent Ovarian Transitional Cell Carcinoma
• Recurrent Ovarian Undifferentiated Carcinoma
• Recurrent Platinum-Resistant Fallopian Tube Carcinoma
• Recurrent Platinum-Resistant Ovarian Carcinoma
• Recurrent Platinum-Resistant Primary Peritoneal Carcinoma
• Recurrent Primary Peritoneal Clear Cell Adenocarcinoma
• Recurrent Primary Peritoneal Endometrioid Adenocarcinoma
• Recurrent Primary Peritoneal High Grade Serous Adenocarcinoma
• Recurrent Primary Peritoneal Low Grade Serous Adenocarcinoma
• Recurrent Primary Peritoneal Transitional Cell Carcinoma
• Recurrent Primary Peritoneal Undifferentiated Carcinoma
• Refractory Fallopian Tube Clear Cell Adenocarcinoma
• Refractory Fallopian Tube Endometrioid Adenocarcinoma
• Refractory Fallopian Tube Mucinous Adenocarcinoma
• Refractory Fallopian Tube Transitional Cell Carcinoma
• Refractory Fallopian Tube Undifferentiated Carcinoma
• Refractory Low Grade Fallopian Tube Serous Adenocarcinoma
• Refractory Ovarian Clear Cell Adenocarcinoma
• Refractory Ovarian Endometrioid Adenocarcinoma
• Refractory Ovarian Mucinous Adenocarcinoma
• Refractory Ovarian Seromucinous Carcinoma
• Refractory Ovarian Transitional Cell Carcinoma
• Refractory Ovarian Undifferentiated Carcinoma
• Refractory Primary Peritoneal Clear Cell Adenocarcinoma
• Refractory Primary Peritoneal Endometrioid Adenocarcinoma
• Refractory Primary Peritoneal High Grade Serous Adenocarcinoma
• Refractory Primary Peritoneal Low Grade Serous Adenocarcinoma
• Refractory Primary Peritoneal Transitional Cell Carcinoma
• Refractory Primary Peritoneal Undifferentiated Carcinoma

• NCT number: NCT04739800
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 10, 2021
• Completion date: January 8, 2025