Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Recurrence

Carcinoma

Adenocarcinoma

Carcinoma, Transitional Cell

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Cystadenocarcinoma, Serous

Adenocarcinoma, Clear Cell

Adenocarcinoma, Mucinous

Cystadenocarcinoma

Fallopian Tube Neoplasms

Carcinoma, Endometrioid

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Cystic, Mucinous, and Serous

Fallopian Tube Diseases

Endometrial Neoplasms

Uterine Neoplasms

Ovarian Cancer

Transitional Cell Carcinoma

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Adenocarcinoma of the Appendix

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Paclitaxel

Albumin-Bound Paclitaxel

Bevacizumab

Antibodies

Doxorubicin

Liposomal doxorubicin

Topotecan

Immunomodulating Agents

Durvalumab

Olaparib

Immunoglobulins

Immunoglobulin G

Immunoglobulins, Intravenous

Poly(ADP-ribose) Polymerase Inhibitors

Maleic acid

Cediranib

Antibodies, Monoclonal

Tubulin Modulators

Antimitotic Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Antineoplastic Agents, Immunological

Immunologic Factors

Topoisomerase I Inhibitors

Protein Kinase Inhibitors

Patients receive paclitaxel 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 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.

Patients receive durvalumab IV over 60 minutes on day 1, cediranib maleate PO QD Monday through Friday, 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.

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.

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.

Biospecimen Collection

Cediranib Maleate

Computed Tomography

Computed Tomography with Contrast

Echocardiography

Magnetic Resonance Imaging

Multigated Acquisition Scan

Pegylated Liposomal Doxorubicin Hydrochloride

Topotecan Hydrochloride

Jung-min Lee

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.

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.

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

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

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Will be presented by Kaplan Meier methods.

Quantified as the binomial proportion of patients with measurable disease at enrollment who have a best overall response of complete response (CR) or partial response (PR).

All adverse events, including severe adverse events and treatment-related adverse events, will be categorized and graded for severity according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

NRG Oncology

National Cancer Institute (NCI)

Spots Global Cancer Trial Database for refractory primary peritoneal high grade serous adenocarcinoma