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

NCT03326193 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2133583000-02-004
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 29

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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  At 18 months

Secondary Outcomes (21)

• Progression Free Survival (PFS) by RECIST v 1.1

  Up to end of study (approximately 79 months)

• Overall Survival (OS)

  Up to end of study (approximately 79 months)

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

  Up to end of study (approximately 79 months)

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

  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)

  Up to end of study (approximately 79 months)

Study Arms (1)

Participants receiving niraparib+ bevacizumab

EXPERIMENTAL

Participants will be administered bevacizumab 15 milligram per kilogram (mg/kg) via a 30 minute (min) intravenous (IV) infusion on Day 1 of each 21-day cycle. Niraparib will be administered orally once a day continuously throughout each 21-day cycle (84-day cycle after amendment 2). On Day 1 of each cycle, niraparib will be administered upon completion of bevacizumab infusion. The starting dose of niraparib will be based on the participant's Baseline actual body weight or platelet count.

Drug: Niraparib; Biological: Bevacizumab

Interventions

Niraparib DRUG

Niraparib will be administered orally once a day continuously throughout each 21 day cycle (84-day cycle after amendment 2). The starting dose of niraparib will be based on the participant's Baseline actual body weight or platelet count. Participants with a Baseline actual body weight of greater than equal to (\>=) 77 kg and Baseline platelet count of \>=150,000/ microliter (μL) will take 300 mg/day (3X100mg) at each dose administration. Participants with a Baseline actual body weight of less than (\<) 77 kg and/or Baseline platelet count of \<150,000/μL will take 200 mg (2X100 mg) at each dose administration.

Also known as: ZEJULA

Participants receiving niraparib+ bevacizumab

Bevacizumab BIOLOGICAL

Maintenance bevacizumab 15 mg/kg will be administered via a 30-minute IV infusion on Day 1 of every 21-day cycle in the absence of progressive disease (PD), unacceptable toxicity, participant withdrawal, Investigator's decision, or death. Bevacizumab will be administered for up to 10 months during the maintenance phase or up to a total of 15 months inclusive of approximately 5 months of bevacizumab received with chemotherapy.

Also known as: Avastin

Participants receiving niraparib+ bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Tesaro, Inc.: lead

Study Sites (29)

GSK Investigational Site

Mobile, Alabama, 36604, United States

Location

GSK Investigational Site

Anchorage, Alaska, 99508, United States

Location

GSK Investigational Site

Mesa, Arizona, 85284, United States

Location

GSK Investigational Site

Burbank, California, 91505, United States

Location

GSK Investigational Site

Los Angeles, California, 90095, United States

Location

GSK Investigational Site

Fort Myers, Florida, 33908, United States

Location

GSK Investigational Site

St. Petersburg, Florida, 33705, United States

Location

GSK Investigational Site

Kansas City, Kansas, 66205, United States

Location

GSK Investigational Site

Detroit, Michigan, 48201, United States

Location

GSK Investigational Site

Detroit, Michigan, 48202, United States

Location

GSK Investigational Site

Jackson, Mississippi, 39216, United States

Location

GSK Investigational Site

Columbia, Missouri, 65212, United States

Location

GSK Investigational Site

Kansas City, Missouri, 64132, United States

Location

GSK Investigational Site

Lebanon, New Hampshire, 03756, United States

Location

GSK Investigational Site

Englewood, New Jersey, 07631, United States

Location

GSK Investigational Site

Morristown, New Jersey, 07962-1956, United States

Location

GSK Investigational Site

Summit, New Jersey, 07962-1956, United States

Location

GSK Investigational Site

Albany, New York, 12208, United States

Location

GSK Investigational Site

Rochester, New York, 14642, United States

Location

GSK Investigational Site

Asheville, North Carolina, 28816, United States

Location

GSK Investigational Site

Columbus, Ohio, 43214, United States

Location

GSK Investigational Site

Oklahoma City, Oklahoma, 73104, United States

Location

GSK Investigational Site

Pittsburgh, Pennsylvania, 15224, United States

Location

GSK Investigational Site

Providence, Rhode Island, 02905, United States

Location

GSK Investigational Site

Chattanooga, Tennessee, 37403, United States

Location

GSK Investigational Site

Kingsport, Tennessee, 37660, United States

Location

GSK Investigational Site

Nashville, Tennessee, 37203, United States

Location

GSK Investigational Site

Fort Worth, Texas, 76104, United States

Location

GSK Investigational Site

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• 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.

  PMID: 35690498 BACKGROUND

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

niraparib; Bevacizumab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: This is an open label study
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2017
• First Posted: October 31, 2017
• Study Start: December 12, 2017
• Primary Completion: December 24, 2020
• Study Completion: July 12, 2024
• Last Updated: July 31, 2025
• Results First Posted: January 19, 2022

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (29)