Olaparib With or Without Bevacizumab in BRCA 1/2 Mutated or Homologous Recombination Deficient Ovarian Cancer

What is the Purpose of this Study?

This study focuses on people with ovarian cancer who have tested positive for BRCA1/2 mutation (change or defect in the BRCA gene) or homologous recombination deficiency (when the body cannot repair breaks in DNA). The goal of the study is to determine whether the use of a drug called olaparib for 1 year can keep the patient’s ovarian cancer from growing or returning as effectively as the usual approach of 2 years. The usual approach for patients who are not in a study is treatment with surgery, radiation, or U.S. Food and Drug Administration (FDA)-approved drugs. Researchers will assess whether olaparib prolongs the time cancer is in remission or duration of life after treatment when compared to the usual approach. Participants will be randomly assigned to 1 of 2 groups. Group 1 will receive olaparib for 2 years; Group 2 will receive olaparib for 1 year.

Eligibility

* Patients with newly diagnosed, pathologically confirmed, Federation of Gynecology and Obstetrics (FIGO) stage III or IV ovarian cancer of the following types:
* High grade serous
* High grade endometrioid, and/or

Inclusion Criteria:

* Patients with newly diagnosed, pathologically confirmed, Federation of Gynecology and Obstetrics (FIGO) stage III or IV ovarian cancer of the following types:
* High grade serous
* High grade endometrioid, and/or
* Other epithelial ovarian cancer with BRCA1/2 deleterious alteration (germline or somatic)
* Submission of pathology report is required
* Ovarian cancer = ovarian, fallopian, or primary peritoneal cancer
* Patients must have:
* Documented variant (tumor or germline) in BRCA1 or BRCA2 that is predicted to be pathogenic or suspected pathogenic
\*\* Submission of testing report is required. AND/OR
* Known HRD deficient tumor determined by any commercial or academic, Clinical Laboratory Improvement Act (CLIA)-certified laboratory (e.g., Myriad MyChoice©) \*\* Submission of testing report is required
* Patient must have undergone cytoreductive surgery (primary or interval)
* Patients must have completed first line platinum-based therapy prior to registration:
* Platinum based chemotherapy course must have consisted of a minimum of 4 treatment cycles and a maximum of 9, although it is strongly recommended that patients receive at least 6 cycles unless medically contraindicated
\*\* For those receiving less than 6 cycles of platinum-based therapy, the reason for this must be documented and could include hematologic toxicity or non-hematologic toxicities directly related to therapy
* Intravenous, intraperitoneal, or neoadjuvant platinum-based chemotherapy is allowed; for weekly therapy, three weeks are considered one cycle
* Patients must not have received an investigational agent during their first line course of chemotherapy
* Patients must have, in the opinion of the investigator, no clinical evidence of disease progression following completion of this chemotherapy course (partial or complete response to platinum-based chemotherapy)
* Patients with treated brain metastases are eligible if follow up brain imaging after central nervous system (CNS) directed therapy shows no evidence of progression and patients are neurologically stable off steroid therapy
* Patients must be randomized at least 3 weeks and no more than 12 weeks after their last dose of chemotherapy (last dose is the day of the last infusion of platinum agent)
* No previous treatment with a PARP inhibitor, including olaparib, niraparib, and rucaparib
* Age ≥ 18
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
* Not pregnant and not nursing
* Absolute neutrophil count (ANC) ≥ 1,500 cells/mm\^3
* Platelets ≥ 100,000 cells/mm\^3
* Hemoglobin ≥ 9 g/dl
* Creatinine clearance (CrCL) of \> 30 mL/min by the Cockcroft-Gault formula
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x institutional ULN may be enrolled)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x institutional ULN
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* No active infection requiring parental antibiotic(s)
* No current evidence of intra-abdominal abscess, abdominal/pelvic fistula (not diverted), gastrointestinal perforation, gastrointestinal (GI) obstruction, and/or need for drainage nasogastric or gastrostomy tube
* No current inability to swallow orally administered medication
* No history of myelodysplastic syndrome and/or acute myeloid leukemia
* No history of allogeneic bone marrow transplant
* Avoid concomitant use of strong or moderate CYP3A inducers at the time of registration and during study treatment with olaparib
* No known hypersensitivity to olaparib or any of the excipients of the product

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Where can I participate?

CS Cancer at Cedars-Sinai Medical Center : Garrett Crook

More about this Clinical Trial

What is the full name of this clinical trial?

NRG-GY036: A Phase III Trial of One vs Two years of Maintenance Olaparib, With or Without Bevacizumab, in Patients with BRCA 1/2 Mutated or Homologous Recombination Deficient Ovarian Cancer Following Response to First Line Platinum-Based Chemotherapy

Study Details

Disease Type/Condition

Ovary

Principal Investigator

Rimel, Bobbie Jo

Co-Investigators

Kristin Taylor, Margaret Liang

Age Group

Adult

Phase

III

IRB Number

STUDY00004063

ClinicalTrials.gov ID

NCT06580314

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

Name

Garrett Crook

Garrett.Crook@cshs.org