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

Running, not enrolling · Phase 2

Conditions studied: Fallopian Tube Mucinous Adenocarcinoma, Ovarian Seromucinous Carcinoma, Platinum-Refractory Fallopian Tube Carcinoma, Platinum-Refractory Ovarian Carcinoma, Platinum-Refractory Primary Peritoneal Carcinoma, Recurrent Fallopian Tube Clear Cell Adenocarcinoma, Recurrent Fallopian Tube Endometrioid Adenocarcinoma, Recurrent Fallopian Tube High Grade Serous 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 High Grade Serous Adenocarcinoma, Recurrent Ovarian Low Grade Serous 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 High Grade Serous 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 High Grade Serous Adenocarcinoma, Refractory Ovarian Low Grade Serous 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

In brief

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.

Key facts

Study ID

NCT04739800

Run by

National Cancer Institute (NCI)

People needed

120

Starts

2021-06-10

Expected to finish

2027-06-25

Last updated by the study team

2026-08-04

Who can join

Age: 18 and older. Sex: female. Healthy volunteers: not accepted.

You may qualify if…

• 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,

You may not qualify if…

• 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 experienced immune-mediated adverse events requiring dose modification or discontinuation.
• For patients who have received prior PARP inhibitor:
• Patients who have required dose modification or dose reduction of olaparib will not be eligible, as they will not be able to start this study at full dose.
• Patients who have required dose reduction of non-olaparib PARP inhibitors for hematologic adverse events will not be eligible (Note: niraparib that is initiated at 200mg daily per weight and platelet guidelines is not considered a dose reduction).
• Patients who required dose-reduction of non-olaparib PARP inhibitors for non-hematologic adverse events may be eligible after discussion with the Study Chair if the treating investigator feels that they could appropriately receive olaparib 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

Where it is running

• Anchorage Radiation Therapy Center — Anchorage, Alaska, United States
• Alaska Breast Care and Surgery LLC — Anchorage, Alaska, United States
• Alaska Oncology and Hematology LLC — Anchorage, Alaska, United States
• Alaska Women's Cancer Care — Anchorage, Alaska, United States
• Anchorage Oncology Centre — Anchorage, Alaska, United States
• Katmai Oncology Group — Anchorage, Alaska, United States
• Providence Alaska Medical Center — Anchorage, Alaska, United States
• Fairbanks Memorial Hospital — Fairbanks, Alaska, United States
• CTCA at Western Regional Medical Center — Goodyear, Arizona, United States
• Cancer Center at Saint Joseph's — Phoenix, Arizona, United States
• Mercy Hospital Fort Smith — Fort Smith, Arkansas, United States
• CHI Saint Vincent Cancer Center Hot Springs — Hot Springs, Arkansas, United States
• University of Arkansas for Medical Sciences — Little Rock, Arkansas, United States
• Mission Hope Medical Oncology - Arroyo Grande — Arroyo Grande, California, United States
• Sutter Auburn Faith Hospital — Auburn, California, United States
• Sutter Cancer Centers Radiation Oncology Services-Auburn — Auburn, California, United States
• Alta Bates Summit Medical Center-Herrick Campus — Berkeley, California, United States
• Providence Saint Joseph Medical Center/Disney Family Cancer Center — Burbank, California, United States
• Sutter Cancer Centers Radiation Oncology Services-Cameron Park — Cameron Park, California, United States
• Eden Hospital Medical Center — Castro Valley, California, United States
• John Muir Medical Center-Concord — Concord, California, United States
• Sutter Davis Hospital — Davis, California, United States
• City of Hope Comprehensive Cancer Center — Duarte, California, United States
• Palo Alto Medical Foundation-Fremont — Fremont, California, United States
• Anchorage Associates in Radiation Medicine — Anchorage, Alaska, United States

Full record on ClinicalTrials.gov

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