Trial Title:
Testing Olaparib for One or Two Years, With or Without Bevacizumab, to Treat Ovarian Cancer
NCT ID:
NCT06580314
Condition:
Fallopian Tube Endometrioid Adenocarcinoma
Fallopian Tube High Grade Serous Adenocarcinoma
FIGO Stage III Ovarian Cancer 2014
FIGO Stage IV Ovarian Cancer 2014
Ovarian Carcinoma
Primary Peritoneal Endometrioid Adenocarcinoma
Primary Peritoneal High Grade Serous Adenocarcinoma
Ovarian High Grade Serous Adenocarcinoma
Conditions: Official terms:
Adenocarcinoma
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Cystadenocarcinoma, Serous
Carcinoma, Endometrioid
Bevacizumab
Olaparib
Poly(ADP-ribose) Polymerase Inhibitors
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Olaparib
Description:
Given PO
Arm group label:
Arm I (olaparib, bevacizumab)
Arm group label:
Arm II (olaparib, bevacizumab)
Other name:
763113-22-0
Other name:
AZD-2281
Other name:
KU-0059436
Other name:
Lynparza
Other name:
Olanib
Other name:
Olaparix
Other name:
PARP inhibitor AZD2281
Intervention type:
Biological
Intervention name:
Bevacizumab
Description:
Given IV
Arm group label:
Arm I (olaparib, bevacizumab)
Arm group label:
Arm II (olaparib, bevacizumab)
Other name:
216974-75-3
Other name:
ABP-215
Other name:
Alymsys
Other name:
Anti-VEGF Humanized Monoclonal Antibody
Other name:
Avastin
Other name:
Aybintio
Other name:
BAT-1706
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Arm I (olaparib, bevacizumab)
Arm group label:
Arm II (olaparib, bevacizumab)
Other name:
Biological Sample Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Arm I (olaparib, bevacizumab)
Arm group label:
Arm II (olaparib, bevacizumab)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
CT
Other name:
CT Scan
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Arm I (olaparib, bevacizumab)
Arm group label:
Arm II (olaparib, bevacizumab)
Other name:
Magnetic Resonance
Other name:
MR
Other name:
MRI
Other name:
MRI Scan
Other name:
NMR Imaging
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Summary:
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.
Detailed description:
PRIMARY OBJECTIVE:
I. To determine investigator assessed progression-free survival (PFS) using Response
Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 (non-inferiority) for one
versus (vs.) two years of maintenance olaparib in the modified intent to treat (ITT)
population.
SECONDARY OBJECTIVES:
I. To evaluate PFS2 and overall survival (OS) in the modified ITT population. II. To
evaluate PFS, PFS2, and OS in the as-treated population. III. To evaluate toxicity,
including rates of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and
other secondary malignancies, in the safety population.
EXPLORATORY OBJECTIVE:
I. To evaluate the moderating effect of physician-choice bevacizumab (as stratified) on
randomized treatment effect estimates.
TRANSLATIONAL OBJECTIVES:
I. To assess BRCA reversion mutations in circulating tumor deoxyribonucleic acid (ctDNA)
as a predictor of poor response in the BRCA mutated (BRCAm) population.
II. To correlate a combined assay assessing quantitative BRCA1 and RAD51C promoter
methylation and pathogenic variants in core homologous recombination repair (HRR) genes
with clinical homologous recombination deficiency (HRD) testing and outcomes in the BRCA
wildtype (BRCAwt) population.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I (REFERENCE): Patients receive olaparib orally (PO) twice daily (BID) on days 1-21
of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease
progression or unacceptable toxicity. Patients may also receive bevacizumab IV on day 1
of each cycle. Cycles of bevacizumab repeat every 21 days for up to 1 year in the absence
of disease progression or unacceptable toxicity. Patients also undergo blood sample
collection and computed tomography (CT) and/or magnetic resonance imaging (MRI)
throughout the study.
ARM II (EXPERIMENTAL): Patients receive olaparib PO BID on days 1-21 of each cycle.
Cycles repeat every 21 days for up to 1 year in the absence of disease progression or
unacceptable toxicity. Patients may also receive bevacizumab IV on day 1 of each cycle.
Cycles of bevacizumab repeat every 21 days for up to 1 year in the absence of disease
progression or unacceptable toxicity. Patients also undergo blood sample collection and
CT and/or MRI throughout the study.
After completion of study treatment, patients are followed up every 3 months for 2 years,
then every 6 months for 3 years.
Criteria for eligibility:
Criteria:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
January 16, 2025
Completion date:
December 31, 2035
Lead sponsor:
Agency:
NRG Oncology
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
NRG Oncology
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06580314
