Clinical trial NCT03326193: A Study of Niraparib Combined With Bevacizumab Maintenance Treatment in Participants With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy
Official title: A Phase 2, Single-arm, Open-label Study to Evaluate the Safety and Efficacy of Niraparib Combined With Bevacizumab as Maintenance Treatment in Patients With Advanced Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer Following Front-line Platinum-based Chemotherapy With Bevacizumab
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Neoplasms
Keywords: Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor
Ovarian Cancer
Primary Peritoneal carcinoma
Fallopian Tube
Vascular endothelial growth factor (VEGF) inhibitor
Bevacizumab
Niraparib
Lead sponsor: Tesaro, Inc.
Sponsor class: INDUSTRY
First posted: 2017-10-31
Enrollment: 105
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Niraparib is an oral inhibitor of poly adenosine diphosphate-ribose polymerase (PARP)-1 and PARP-2. This study will evaluate safety and efficacy of niraparib combined with bevacizumab as maintenance treatment in participants with advanced (stage IIIB-IV) ovarian cancer, fallopian tube cancer, or primary peritoneal cancer following front-line platinum-based chemotherapy with bevacizumab. Eligible participants who achieve complete response (CR), partial response (PR), or no evidence of disease (NED) following treatment with platinum-based chemotherapy in addition to bevacizumab will be enrolled in the study and will receive maintenance treatment with niraparib (for up to 3 years) combined with bevacizumab (for up to 10 months during the maintenance phase or up to a total of 15 months inclusive of the approximately 5 months of bevacizumab received with chemotherapy) or until disease progression, unacceptable toxicity, participant withdrawal, Investigator's decision, or death, whichever comes first. Participants who have not progressed after 3 years of niraparib maintenance treatment may continue with niraparib beyond 3 years if they are benefiting from treatment, upon consultation with Sponsor.


Eligibility criteria: 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

Primary outcomes:
measure: Progression Free Survival (PFS) Rate
timeFrame: At 18 months
Secondary outcomes:
measure: Progression Free Survival by RECIST v 1.1
timeFrame: Up to 3 years
measure: Overall Survival (OS)
timeFrame: Up to 3 years
measure: RECIST or Cancer Antigen (CA)-125 Progression Free Survival
timeFrame: Up to 3 years
measure: Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI)
timeFrame: Baseline and up to 3 years
measure: Time to First Subsequent Therapy (TFST)
timeFrame: Up to 3 years
measure: Time to Second Subsequent Therapy (TSST)
timeFrame: Up to 3 years
measure: Number of Participants With Non-serious Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to a maximum of 33.68 months
measure: Number of Participants With TEAEs Leading to Niraparib Treatment Discontinuation
timeFrame: Up to a maximum of 33.68 months
measure: Number of Participants With TEAEs Leading to Niraparib Dose Reductions
timeFrame: Up to a maximum of 33.68 months
Other outcomes:
Locations:
city: Mobile
country: United States
facility: GSK Investigational Site
state: Alabama
city: Anchorage
country: United States
facility: GSK Investigational Site
state: Alaska
city: Mesa
country: United States
facility: GSK Investigational Site
state: Arizona
city: Burbank
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Fort Myers
country: United States
facility: GSK Investigational Site
state: Florida
city: Saint Petersburg
country: United States
facility: GSK Investigational Site
state: Florida
city: Detroit
country: United States
facility: GSK Investigational Site
state: Michigan
city: Detroit
country: United States
facility: GSK Investigational Site
state: Michigan
city: Jackson
country: United States
facility: GSK Investigational Site
state: Mississippi
city: Columbia
country: United States
facility: GSK Investigational Site
state: Missouri
city: Kansas City
country: United States
facility: GSK Investigational Site
state: Missouri
city: Kansas City
country: United States
facility: GSK Investigational Site
state: Missouri
city: Lebanon
country: United States
facility: GSK Investigational Site
state: New Hampshire
city: Englewood
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Morristown
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Summit
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Albany
country: United States
facility: GSK Investigational Site
state: New York
city: Rochester
country: United States
facility: GSK Investigational Site
state: New York
city: Asheville
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Columbus
country: United States
facility: GSK Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Providence
country: United States
facility: GSK Investigational Site
state: Rhode Island
city: Chattanooga
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Kingsport
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Fort Worth
country: United States
facility: GSK Investigational Site
state: Texas
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Hardesty MM, Krivak TC, Wright GS, Hamilton E, Fleming EL, Belotte J, Keeton EK, Wang P, Gupta D, Clements A, Gray HJ, Konecny GE, Moore RG, Richardson DL. OVARIO phase II trial of combination niraparib plus bevacizumab maintenance therapy in advanced ovarian cancer following first-line platinum-based chemotherapy with bevacizumab. Gynecol Oncol. 2022 Aug;166(2):219-229. doi: 10.1016/j.ygyno.2022.05.020. Epub 2022 Jun 9.