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

Running, not enrolling · Phase 2

Conditions studied: Fallopian Tube Endometrioid Tumor, Fallopian Tube High Grade Serous Adenocarcinoma, Malignant Ovarian Endometrioid Tumor, Ovarian High Grade Serous Adenocarcinoma, Platinum-Sensitive Fallopian Tube Carcinoma, Platinum-Sensitive Ovarian Carcinoma, Platinum-Sensitive Primary Peritoneal Carcinoma, Primary Peritoneal High Grade Serous Adenocarcinoma, 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

In brief

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.

Key facts

Study ID

NCT04034927

Run by

National Cancer Institute (NCI)

People needed

61

Starts

2019-12-04

Expected to finish

2027-02-21

Last updated by the study team

2026-07-31

Who can join

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

You may qualify if…

• Patients must have platinum-sensitive, recurrent high-grade serous or high-grade endometrioid (grade 3) ovarian, primary peritoneal, or fallopian tube cancer. Patients with other histologies are also eligible, provided that the patient has a known deleterious germline or somatic BRCA1 or BRCA2 mutation identified through testing at a clinical laboratory. Submission of BRCA testing results (germline and/or somatic) is required for all patients.
• Platinum-sensitive disease defined as no clinical or radiographic evidence of disease recurrence for > 6 months (or 182 days) after last receipt of platinum-based therapy. The date should be calculated from the last administered dose of platinum therapy.
• Patients must have had response (complete or partial) to their prior line of platinum therapy and cannot have had progression through prior platinum-based therapy.
• Patients must have RECIST 1.1 measurable disease. Patients with biochemical recurrence based on CA125 levels alone are not eligible.
• Prior therapy:
• Prior chemotherapy must have included a first-line platinum-based regimen with or without consolidation chemotherapy.
• Prior bevacizumab therapy as a component of frontline or recurrent treatment is permitted.
• Patients may have received an unlimited number of platinum-based therapies in the recurrent setting.
• Patients may have received up to one non-platinum-based line of therapy in the recurrent setting. Prior hormonal therapy will not be counted as this non-platinum-based line.
• Prior treatment with a PARP inhibitor:
• Patients may not have had a prior PARP inhibitor in the recurrent setting.
• Prior use of a PARP inhibitor in the upfront maintenance setting is allowed for women with a confirmed BRCA1 or BRCA2 germline or somatic mutation.
• Women who received a PARP inhibitor for maintenance therapy in the frontline setting must have received at least one other chemotherapy regimen for recurrence prior to enrolling on this trial.
• Patients who demonstrated disease progression while on a PARP inhibitor are excluded.
• Prior hormonal-based therapy for ovarian, primary peritoneal, or fallopian tube cancer is acceptable.
• Age >= 18.
• Body weight > 30 kg.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Absolute neutrophil count (ANC) >= 1,500/mcl (within 14 days prior to enrollment)
• Platelets >= 100,000/mcl (within 14 days prior to enrollment)
• Hemoglobin >= 10 g/dL (within 14 days prior to enrollment)
• Note: blood transfusions are not permitted within 28 days prior to enrollment
• Creatinine =< 1.5 x institutional/laboratory upper limit of normal (ULN) (within 14 days prior to enrollment)
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 14 days prior to enrollment)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 times institutional ULN (within 14 days prior to enrollment)

You may not qualify if…

• Active infection requiring antibiotic therapy (except for uncomplicated urinary tract infections), including tuberculosis.
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; and cirrhosis. For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• Hormonal therapy directed at treatment for the cancer must be discontinued at least 28 days prior to enrollment. Hormone replacement therapy for symptom management is permitted.
• Any other therapy directed at treating the cancer including chemotherapy, biologic/targeted agents, and immunologic agents, unless discontinued at least 28 days prior to enrollment.
• Any radiation therapy unless discontinued at least 28 days prior to enrollment.
• Major surgical procedure within 28 days prior to enrollment.
• Current or prior use of immunosuppressive medication within 14 days before enrollment. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (i.e. intra-articular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10mg/day of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (i.e. computed tomography [CT] scan contrast allergy premedication).
• 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.
• Patients with autoimmune disease (e.g., psoriasis, extensive atopic dermatitis, severe asthma, inflammatory bowel disease [IBD], multiple sclerosis [M.S.], uveitis, vasculitis) requiring concurrent use of any systemic immunosuppressants or steroids are excluded from the study. Patients with vitiligo, mild, intermittent asthma requiring only occasional beta-agonist inhaler use, or mild localized eczema are eligible.
• Any patient with an allogeneic (allo)-transplant of any kind is excluded, including xenograft heart valve.
• Chronic use of immune-suppressive drugs (i.e. systemic corticosteroids) for the management of cancer or non-cancer related illnesses (i.e. chronic obstructive pulmonary disease [COPD]).
• Note: ongoing steroid use for the management of brain metastases is not permitted.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib or tremelimumab.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring adverse events (AEs) or compromise the ability of the patient to give written informed consent.
• Subjects must not have evidence of bowel obstruction on imaging or symptoms consistent with a bowel obstruction. Additional workup to rule this out is not required.
• Known potent CYP3A4 inhibitors or inducers must be discontinued prior to starting treatment.
• Symptoms associated with toxicities (> Common Terminology Criteria for Adverse Event [CTCAE version (v) 5.] grade 2) caused by prior cancer therapy, excluding alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
• Patients with grade >= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Chair.
• Patients who are receiving any other investigational agent.
• Resting electrocardiogram (ECG) with corrected QT interval (QTc) > 470 msec on two or more time points within a 24-hour period, or a family history of long QT syndrome. If an initial ECG is within normal limits, a repeat ECG is not required.
• Patients who have previously received anti-CTLA-4 antibody therapy.
• Blood transfusions are not permitted within 28 days prior to study enrollment.

Where it is running

• UC Irvine Health/Chao Family Comprehensive Cancer Center — Orange, California, United States
• UCHealth University of Colorado Hospital — Aurora, Colorado, United States
• Hartford Hospital — Hartford, Connecticut, United States
• Augusta University Medical Center — Augusta, Georgia, United States
• University of Chicago Comprehensive Cancer Center — Chicago, Illinois, United States
• Washington University School of Medicine — St Louis, Missouri, United States
• University of New Mexico Cancer Center — Albuquerque, New Mexico, United States
• Memorial Sloan Kettering Cancer Center — New York, New York, United States
• UHHS-Chagrin Highlands Medical Center — Beachwood, Ohio, United States
• Case Western Reserve University — Cleveland, Ohio, United States
• Cleveland Clinic Foundation — Cleveland, Ohio, United States
• Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States
• University of Oklahoma Health Sciences Center — Oklahoma City, Oklahoma, United States
• Thomas Jefferson University Hospital — Philadelphia, Pennsylvania, United States
• UPMC Hillman Cancer Center — Pittsburgh, Pennsylvania, United States
• Women and Infants Hospital — Providence, Rhode Island, United States
• UT MD Anderson Cancer Center — Houston, Texas, United States
• University of Virginia Cancer Center — Charlottesville, Virginia, United States
• VCU Massey Comprehensive Cancer Center — Richmond, Virginia, United States
• Medical College of Wisconsin — Milwaukee, Wisconsin, United States

Full record on ClinicalTrials.gov

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