NCT03326193 - A Study of Niraparib Combined With Bevacizumab Maintenance Treatment in Participants With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy | Crick

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Participants must be female, be greater than equal to (\>=) 18 years of age, be able to understand the study procedures, and agree to participate in the study by providing written informed consent. * Participants must have newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) Stage IIIB to IV epithelial ovarian, fallopian tube, or peritoneal cancer and have recovered from debulking surgery. * Participants must have high-grade serous or endometrioid or high-grade predominantly serous or endometrioid histology, regardless of homologous recombination deficiency (HRD) or germline breast cancer susceptibility gene (gBRCA) mutation status. Participants with non mucinous epithelial ovarian cancer and gBRCA mutation are eligible. * Participants must have completed front-line, platinum-based chemotherapy with CR, PR, or NED and have first study treatment dose within 12 weeks of the first day of the last cycle of chemotherapy: * a. A platinum-based regimen must have consisted of a minimum of 6 and a maximum of 9 treatment cycles. Participants who discontinued platinum-based therapy early as a result of non hematologic toxicity specifically related to the platinum regimen (ie, neurotoxicity or hypersensitivity) are eligible if they have received a minimum of 4 cycles of the platinum regimen. * b. IV, intraperitoneal, or neoadjuvant platinum-based chemotherapy is allowed; for weekly therapy, 3 weeks is considered 1 cycle. Interval debulking is allowed. * Participants must have received, prior to enrollment, a minimum of 3 cycles of bevacizumab in combination with the last 3 cycles of platinum-based chemotherapy. Participants who undergo interval debulking surgery are eligible if they have received only 2 cycles of bevacizumab in combination with the last 3 cycles of platinum-based chemotherapy. * Participant must have had 1 attempt at optimal debulking surgery. * Participant must have either CA-125 in the normal range or CA-125 decrease by more than 90% during front-line therapy that is stable for at least 7 days (ie, no increase \> 15% from nadir). * Participant must have adequate organ function. * Participant must have an Eastern Cooperative Oncology Group (ECOG) score of 0 or 1. * Participant must have normal blood pressure or well-controlled hypertension. * Participant must agree to complete patient-reported outcome (PROs) (Functional Assessment of Cancer Therapy-Ovarian Symptom Index \[FOSI\] questionnaire) throughout the study, including after study treatment discontinuation. * Participant must be able to take oral medication. * Participant must agree to undergo tumor HRD testing at screening. The tumor sample must be confirmed to be available during the screening period and submitted after the participant has been enrolled. Participants do not have to wait for the HRD test result to be enrolled. If archival tumor tissue is not available for testing, the participant must agree to undergo a fresh biopsy. * Participant of childbearing potential must have a negative serum or urine pregnancy test (beta human chorionic gonadotropin) within 72 hours prior to receiving the first dose of study treatment. * Participants must be postmenopausal, free from menses for \> 1 year, surgically sterilized, or willing to use adequate contraception to prevent pregnancy or must agree to abstain from activities that could result in pregnancy throughout the study, starting with enrollment through 180 days after the last dose of study treatment. Exclusion Criteria: * Participants with ovarian tumors of non-epithelial origin (eg, germ cell tumor) or any low grade tumors. * Participants with clinically significant cardiovascular disease (eg, significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or unstable angina \< 6 months to enrollment, New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade II or greater peripheral vascular disease, and history of cerebrovascular accident (CVA) within 6 months). * Participants with gastrointestinal disorders or abnormalities that would interfere with absorption of study treatment. * History of bowel obstruction, including sub-occlusive disease, related to the underlying disease or history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscesses. Evidence of rectosigmoid involvement by pelvic examination or bowel involvement on computed tomography (CT) scan or clinical symptoms of bowel obstruction. * Participant has proteinuria as demonstrated by urine protein:creatinine ratio \>= 1.0 at screening or urine dipstick for proteinuria ≥ 2 (participants discovered to have \>=2 proteinuria on dipstick at baseline should undergo a 24-hour urine collection and must demonstrate \< 2 gram (g) of protein in 24 hours to be eligible). * Participant has any known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML). * Participant has received treatment previously with a PARP inhibitor. * Other than ovarian cancer, the participant has been diagnosed or treated for invasive cancer less than 5 years prior to study enrollment. Participants with cervical carcinoma in situ, non melanomatous skin cancer, and ductal carcinoma in situ definitively treated are allowed. * Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, non malignant systemic disease, or active, uncontrolled infection. * Participant has known contraindication to PARP inhibitors or (VEGF inhibitors. * Participant is at increased bleeding risk due to concurrent conditions (eg, major injuries or surgery within the past 28 days prior to start of study treatment, history of CVA, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months). * Participant is immunocompromised (participants with splenectomy are allowed). * Participant has known, active hepatic disease (ie, hepatitis B or C). * Participant has a QT interval prolongation \> 480 milliseconds (ms) at screening. If a participant has a prolonged QT interval and the prolongation is deemed to be due to a pacemaker upon Investigator evaluation (ie, the participant otherwise has no cardiac abnormalities), then the participant may be eligible to participate in the study following discussion with the Medical Monitor. * Participant is pregnant, or expecting to conceive children while receiving study drug or for 180 days after the last dose of study drug ; additionally, female participant should not breastfeed during treatment with niraparib and for 30 days after receipt of the last dose due to the potential for serious adverse reactions from niraparib in breastfed infants

Outcomes

Primary Outcomes

Progression Free Survival (PFS) Rate

PFS rate at 18 months is defined as the percentage of participants who have not progressed or died within 18 months after niraparib combined with bevacizumab treatment initiation. Progression was assessed by response evaluation criteria in solid tumors (RECIST) version (v) 1.1 criteria per Investigator assessment and defined as a 20 percent (%) increase in the sum of the diameter of target lesions or unequivocal progression of existing non-target lesions. Survival rate is the percentage of participants without progression assessed by RECIST v1.1 or death by the landmark timepoint. Confidence intervals was constructed using exact method.

Time frame: At 18 months

Secondary Outcomes

Progression Free Survival (PFS) by RECIST v 1.1

PFS was defined as the time from treatment initiation with niraparib combined with bevacizumab to the earlier date of assessment of progression, as assessed by RECIST v1.1 criteria, based on Investigator assessment, or death by any cause in the absence of progression.

Time frame: Up to end of study (approximately 79 months)

Overall Survival (OS)

OS was defined as the date of initiation of niraparib treatment in combination with bevacizumab to the date of death by any cause.

Time frame: Up to end of study (approximately 79 months)

RECIST or Cancer Antigen (CA)-125 Progression Free Survival

RECIST or CA-125 progression-free survival is defined as the time from initiation of niraparib treatment in combination with bevacizumab to the earliest date of progression assessed by RECIST v1.1 or CA-125 progression or death by any cause. CA-125 progression is defined as participants with elevated CA-125 pretreatment and normalization of CA-125 that must show evidence of CA-125 ≥ 2 × upper limit of normal (ULN) on 2 occasions at least 1 week apart OR elevated CA-125 pretreatment that never normalizes and must show evidence of CA-125 ≥ 2 × the nadir value on 2 occasions at least 1 week apart OR elevated CA-125 in the normal range pretreatment that must show evidence of CA-125 ≥ 2 × ULN on 2 occasions at least 1 week apart.

Time frame: Up to end of study (approximately 79 months)

Change From Baseline (CFB) in Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI)

FOSI is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants responded to their symptom experience over the past 7 days using a 5-point Likert scale scored from "not at all" (0) to "very much" (4). FOSI score was calculated as sum of item scores multiplied by 8 divided by number of items answered. The FOSI score ranged from 0 (severely symptomatic) to 32 (asymptomatic). A higher score indicated a better quality of life (QoL). Baseline (Day 1) is defined as the most recent measurement prior to the first administration of study drug (including Cycle 1 Day 1).

Time frame: Baseline (Day 1), Cycles 3, 5, 7, 9, 13, 17, 21, 25, 29 (Each Cycle was of 21 days) and end of treatment (70 months)

Time to First Subsequent Therapy (TFST)

TFST was defined as the date of initiation of niraparib treatment in combination with bevacizumab treatment in the current study to the start date of the first subsequent anticancer therapy.

Time frame: Up to end of study (approximately 79 months)

Time to Second Subsequent Therapy (TSST)

TSST was defined as the date of initiation of treatment of niraparib in combination with bevacizumab treatment in the current study to the start date of the second subsequent anticancer therapy.

Time frame: Up to end of study (approximately 79 months)

Percentage of Participants With Treatment-emergent Adverse Events (TEAEs), Non-serious TEAEs and Treatment-emergent Serious Adverse Events (TESAEs)

Adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. TEAEs is any AE that occurred for the first time after at least 1 dose of study treatment administration and until treatment duration. TEAEs which were not serious were considered as non-serious TEAEs. TESAE is defined as any untoward medical occurrence that, at any dose may result in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity or is congenital anomaly/birth defect or any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) coding system. Percentages are rounded off to the nearest decimal point.

Time frame: Up to end of treatment (70 months)

Number of Participants With TEAEs Leading to Niraparib Treatment Discontinuation

AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. TEAE is any AE that occurred for the first time after at least 1 dose of study treatment administration. AEs were coded using the MedDRA coding system.

Time frame: Up to end of treatment (70 months)

Number of Participants With TEAEs Leading to Niraparib Dose Reductions

Time frame: Up to end of treatment (70 months)

Number of Participants With AEs of Special Interest (AESI)

AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESIs of scientific and medical concern related to the treatment were monitored, and rapidly communicated by investigator to sponsor. AEs were coded using the MedDRA coding system.

Time frame: Up to end of treatment (70 months)

Change From Baseline (CFB) in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Blood pressures (DBP and SBP) were measured after resting for at least 5 minutes in a supine or semi-recumbent position. Baseline (Day 1) is defined as the most recent measurement prior to the first administration of study drug (including Cycle 1 Day 1).