Testing Olaparib for One or Two Years, With or Without Bevacizumab, to Treat Ovarian Cancer
Testing Olaparib for One or Two Years, With or Without Bevacizumab, to Treat Ovarian Cancer
This phase III trial compares the effect of olaparib for one year versus two years, with or without bevacizumab, for the treatment of BRCA 1/2 mutated or homologous recombination deficient stage III or IV ovarian cancer. Olaparib is a polyadenosine 5'-diphosphoribose polymerase (PARP) enzyme inhibitor and may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving olaparib for one year with or without bevacizumab may be effective in treating patients with BRCA 1/2 mutated or homologous recombination deficient stage III or IV ovarian cancer, when compared to two years of olaparib.
Gynecologic,
Ovarian
Phase III
Adults
Mol. targeted/Immunotherapy/Biologics
Bevacizumab,
Olaparib
Crispens, Marta
International
Vanderbilt University
06-19-2025
Eligibility
18 Years and older
ALL
false
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 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 (deleterious alteration) * Submission of testing report is required. OR * BRCA 1/2 wildtype AND 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
Patients must have: * Documented variant (tumor or germline) in BRCA1 or BRCA2 that is predicted to be pathogenic or suspected pathogenic (deleterious alteration) * Submission of testing report is required. OR * BRCA 1/2 wildtype AND 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)
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 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 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 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 following completion of this chemotherapy course (partial or complete response to platinum-based chemotherapy)
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)
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
No previous treatment with a PARP inhibitor, including olaparib, niraparib, and rucaparib
Age 18
Age 18
Eastern Cooperative Oncology Group (ECOG) performance status of 2
Eastern Cooperative Oncology Group (ECOG) performance status of 2
Not pregnant and not nursing
Not pregnant and not nursing
Absolute neutrophil count (ANC) 1,500 cells/mm\^3
Absolute neutrophil count (ANC) 1,500 cells/mm\^3
Platelets 100,000 cells/mm\^3
Platelets 100,000 cells/mm\^3
Hemoglobin 9 g/dl
Hemoglobin 9 g/dl
Creatinine clearance (CrCL) of > 30 mL/min by the Cockcroft-Gault formula
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)
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
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
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 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 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 current inability to swallow orally administered medication
No history of myelodysplastic syndrome and/or acute myeloid leukemia
No history of myelodysplastic syndrome and/or acute myeloid leukemia
No history of allogeneic bone marrow transplant
No history of allogeneic bone marrow transplant
No concomitant use of strong or moderate CYP3A inducers
No concomitant use of strong or moderate CYP3A inducers
No known hypersensitivity to olaparib or any of the excipients of the product
No known hypersensitivity to olaparib or any of the excipients of the product
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 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 (deleterious alteration) * Submission of testing report is required. OR * BRCA 1/2 wildtype AND 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
Patients must have: * Documented variant (tumor or germline) in BRCA1 or BRCA2 that is predicted to be pathogenic or suspected pathogenic (deleterious alteration) * Submission of testing report is required. OR * BRCA 1/2 wildtype AND 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)
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 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 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 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 following completion of this chemotherapy course (partial or complete response to platinum-based chemotherapy)
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)
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
No previous treatment with a PARP inhibitor, including olaparib, niraparib, and rucaparib
Age 18
Age 18
Eastern Cooperative Oncology Group (ECOG) performance status of 2
Eastern Cooperative Oncology Group (ECOG) performance status of 2
Not pregnant and not nursing
Not pregnant and not nursing
Absolute neutrophil count (ANC) 1,500 cells/mm\^3
Absolute neutrophil count (ANC) 1,500 cells/mm\^3
Platelets 100,000 cells/mm\^3
Platelets 100,000 cells/mm\^3
Hemoglobin 9 g/dl
Hemoglobin 9 g/dl
Creatinine clearance (CrCL) of > 30 mL/min by the Cockcroft-Gault formula
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)
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
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
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 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 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 current inability to swallow orally administered medication
No history of myelodysplastic syndrome and/or acute myeloid leukemia
No history of myelodysplastic syndrome and/or acute myeloid leukemia
No history of allogeneic bone marrow transplant
No history of allogeneic bone marrow transplant
No concomitant use of strong or moderate CYP3A inducers
No concomitant use of strong or moderate CYP3A inducers
No known hypersensitivity to olaparib or any of the excipients of the product
No known hypersensitivity to olaparib or any of the excipients of the product
