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

  • STATUS
    Recruiting
  • End date
    Apr 30, 2022
  • participants needed
    164
  • sponsor
    National Cancer Institute (NCI)
Updated on 5 December 2021

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.

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.

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.

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.

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.

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

Details
Condition Fallopian Tube Mucinous Adenocarcinoma, Ovarian Seromucinous Carcinoma, Recurrent Ovarian Endometrioid Adenocarcinoma, Recurrent Ovarian Transitional Cell Carcinoma, Recurrent Low Grade Fallopian Tube Serous Adenocarcinoma, Recurrent Low Grade Ovarian Serous Adenocarcinoma, Recurrent Ovarian Clear Cell Adenocarcinoma, Recurrent Ovarian Mucinous Adenocarcinoma, Recurrent Primary Peritoneal Low Grade Serous Adenocarcinoma, Recurrent High Grade Ovarian Serous Adenocarcinoma, Recurrent Fallopian Tube Endometrioid Adenocarcinoma, Recurrent Primary Peritoneal Endometrioid Adenocarcinoma, Recurrent Fallopian Tube Clear Cell Adenocarcinoma, Recurrent Fallopian Tube Undifferentiated Carcinoma, Recurrent Ovarian Undifferentiated Carcinoma, Recurrent Primary Peritoneal Clear Cell Adenocarcinoma, Recurrent Primary Peritoneal Undifferentiated Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Fallopian Tube Mucinous Adenocarcinoma, Recurrent Fallopian Tube Transitional Cell Carcinoma, Recurrent High Grade Fallopian Tube Serous Adenocarcinoma, Recurrent Ovarian Seromucinous Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Recurrent Primary Peritoneal High Grade Serous Adenocarcinoma, Recurrent Primary Peritoneal Transitional Cell 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 High Grade Fallopian Tube Serous Adenocarcinoma, Refractory High Grade Ovarian Serous Adenocarcinoma, Refractory Low Grade Fallopian Tube Serous Adenocarcinoma, Refractory Low Grade Ovarian 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, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Platinum-Refractory Ovarian Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Fallopian Tube Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma, Recurrent Platinum-Resistant Primary Peritoneal Carcinoma
Treatment pegylated liposomal doxorubicin hydrochloride, Paclitaxel, durvalumab, topotecan hydrochloride, cediranib maleate, olaparib
Clinical Study IdentifierNCT04739800
SponsorNational Cancer Institute (NCI)
Last Modified on5 December 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Women with recurrent/persistent platinum-resistant ovarian, primary peritoneal, or fallopian tube cancers; platinum-resistant disease is defined as progression within < 6 months from completion of platinum based therapy. The date should be calculated from the last administered dose of platinum therapy
Patients must have histologically or cytologically confirmed ovarian cancer, peritoneal cancer or fallopian tube cancer and must have a histological diagnosis of high grade serous, grade 3 endometrioid or clear cell carcinoma based on local histopathological findings. Patients with low grade serous, grade 1 or 2 endometrioid, mixed epithelial, undifferentiated carcinoma, or mucinous carcinoma histologies are also eligible, provided that the patient has a known deleterious BRCA1 or BRCA2 mutation identified through testing at a clinical laboratory. Histologic confirmation of the original primary tumor is required via the pathology report (upload of report required). Confirmation of BRCA1 and BRCA2 germline and/or somatic mutation status and hormone receptor (HR) status is required for all entered patients (if available) via testing report (upload of report[s] required)
Evaluable disease - defined as RECIST 1.1 measurable disease OR non-measurable disease (defined as solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions OR ascites and/or pleural effusion that has been pathologically demonstrated to be disease-related in the setting of a CA125 >= 2 x upper limit of normal [ULN])
Prior therapy
At least two prior treatment regimens (including primary therapy) but up to 5 lines of systemic anticancer therapy. Hormonal therapy (such as tamoxifen, aromatase inhibitors) will not count as a previous treatment regimen
Prior use of bevacizumab in the upfront or recurrent setting is required
Prior use of PARP inhibitor is allowed
Prior use of immune checkpoint blockade (e.g., a PD-L1/PD-1inhibitor or a CTLA-4 inhibitor) is allowed
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Absolute neutrophil count (ANC) >= 1,500/mcL
Hemoglobin > 10 g/dL
Platelets >= 100,000/mcL
Creatinine clearance (CrCL) or estimated glomerular filtration rate (eGFR) of > 50 mL/min estimated using either the Cockcroft-Gault equation, the Modification of Diet in Renal Disease Study, or as reported in the comprehensive metabolic panel/basic metabolic panel (eGFR)
Urine protein: creatinine ratio (UPC) of =< 1
Total serum bilirubin level =< 1.5 x ULN (patients with known Gilbert's disease who have bilirubin level =< 3 x ULN may be enrolled)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN
Age >= 18 years
Body weight > 30 kg
Adequately controlled blood pressure (systolic blood pressure [SBP] =< 140; diastolic blood pressure [DBP] =< 90 mmHg) on a maximum of three antihypertensive medications. Patients must have a BP of =< 140/90 mmHg taken in the clinic setting by a medical professional within 2 weeks prior to study registration. It is strongly recommended that patients who are on three antihypertensive medications be followed by a cardiologist or a primary care physician for management of BP while on protocol. Patients must be willing and able to check and record daily blood pressure readings. BP cuffs will be provided to patients randomized to the cediranib-containing arms
Adequately controlled thyroid dysfunction with no symptoms of thyroid dysfunction and normal thyroid stimulating hormone (TSH). If TSH is not within normal range despite no symptoms of thyroid dysfunction, normal free T4 level is required
Able to swallow and retain oral medications and no gastrointestinal (GI) illnesses that would preclude absorption of olaparib and cediranib as judged by treating physician
Toxicities of prior therapy (excepting alopecia and vitiligo), should be resolved to less than or equal to grade 1 as per Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Women of childbearing potential (WOCBP) must agree to use two forms of birth control (hormonal or barrier method of birth control; abstinence). Note: Definition of women of no longer having childbearing potential: Postmenopausal or evidence of non-childbearing status for women of childbearing potential as confirmed by a negative urine or serum pregnancy test within 7 days prior to start of study treatment. Postmenopausal is defined as: Age >= 60 years, or age < 60 with any one or more of the conditions below
Amenorrhoeic for >= 1 year in the absence of chemotherapy and/or hormonal treatments
Luteinizing hormone and/or follicle stimulating hormone and/or estradiol levels in the post-menopausal range
Radiation-induced oophorectomy with last menses > 1 year ago
Chemotherapy-induced menopause with > 1 year interval since last menses
Surgical sterilization (bilateral oophorectomy or hysterectomy)
The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and authorization permitting release of personal health information

Exclusion Criteria

Primary platinum-refractory disease defined as progression during first-line platinum-based chemotherapy
Rising CA-125 only without RECIST 1.1 evaluable disease
Prior therapy
Patients who have had chemotherapy, investigational drugs or radiotherapy within 3 weeks prior to study registration or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier
Patients may not have had hormonal therapy within 2 weeks of study registration. Patients receiving raloxifene for bone health as per Food and Drug Administration (FDA) indication may remain on raloxifene absent other drug interactions
Prior use of concurrent olaparib and cediranib combination
Patients who have had prior PARP inhibitor or immune checkpoint blockade requiring dose modifications as they cannot start this study at full dose
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 3 months prior to study registration
Current signs and/or symptoms of bowel obstruction or signs and/or symptoms of bowel obstruction within 3 months of study registration except temporary (< 24 hr) improved with medical management, within last 3 months
Any prior grade >= 3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE > grade 1
Dependency on IV hydration or total parenteral nutrition (TPN)
Pregnant women. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with these drugs, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
Patients with untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on computed tomography (CT) or magnetic resonance imaging (MRI) scans should not be included on this study, since neurologic dysfunction may confound the evaluation of neurologic and other adverse events. Patients with treated brain metastases and resolution of any associated symptoms must demonstrate stable post-therapeutic imaging for at least 6 months following therapy prior to starting study registration
Patients who have the following clinical conditions are considered to be at increased risk for cardiac toxicities. Patients with any cardiac history of the following
conditions
History of myocardial infarction or myocarditis within six months of study registration
Unstable angina
Resting electrocardiogram (ECG) with clinically significant abnormal findings
New York Heart Association functional classification of III or IV
If cardiac function assessment is clinically indicated or performed: left ventricular ejection fraction (LVEF) less than normal per institutional guidelines, or < 55%, if threshold for normal not otherwise specified by institutional guidelines. Patients with the following risk factors should have a baseline cardiac function assessment
Prior treatment with anthracyclines
Prior treatment with trastuzumab or T-DM1
Prior central thoracic radiation therapy (RT), including RT to the heart
History of myocardial infarction within 6 to 12 months (Patients with history of myocardial infarction within 6 months are excluded from the study)
Prior history of impaired cardiac function
History of stroke or transient ischemic attack within six months of study registration
Clinically significant peripheral vascular disease or vascular disease (aortic aneurysm or aortic dissection)
Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study treatment. Patients must have recovered from any effects of any major surgery and surgical wound should have healed prior to starting treatment. Note: Local surgery of isolated lesions for palliative intent is acceptable
Evidence of coagulopathy or bleeding diathesis. Therapeutic anticoagulation for prior thromboembolic events, including warfarin, is permitted. Patients receiving warfarin are recommended to have careful monitoring of international normalized ratio (INR)
Evidence suggestive of myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) on peripheral blood smear or bone marrow biopsy, if clinically indicated. No prior allogeneic bone marrow transplant or double umbilical cord blood transplantation (dUBCT)
Human immunodeficiency virus (HIV) positive patients due to potential drug and drug interactions
Patients may not use any complementary or alternative medicines including natural herbal products or folk remedies as they may interfere with the effectiveness of the study treatments
Receipt of live attenuated vaccine within 30 days prior to the first dose of study treatment. Note: Patients, if enrolled, should not receive live vaccine whilst receiving study treatment and up to 30 days after the last dose of study treatment
Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (other than atrial fibrillation with controlled ventricular rate), or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring adverse events or compromise the ability of the patient to given written informed consent
Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4. Dihydropyridine calcium-channel blockers are permitted for management of hypertension
Current or prior use of immunosuppressive medication within 14 days of study registration. The following are exceptions to this criterion
Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
History of allergic reactions attributed to compounds of similar chemical or biologic composition to durvalumab, olaparib, or cediranib
Patients with active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis [TB] testing in line with local practice), hepatitis B (known positive hepatitis B virus [HBV] surface antigen (HBsAg) result), or hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for hepatitis C virus (HCV) ribonucleic acid (RNA)
Patients who have a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis
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Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

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If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

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Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

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