Ovarian NeoplasmsPhase 2NCT03326193
A Study of Niraparib Combined With Bevacizumab Maintenance Treatment in Participants With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy
A Phase 2 study testing Niraparib and Bevacizumab in people with Ovarian Neoplasms, run by Tesaro, Inc. at 29 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Neoplasms
- What is being tested?
- Niraparib and Bevacizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 105 participants
- Where
- 29 sitesUnited States
- Study dates
- 12 Dec 2017to 12 Jul 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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
Trial locations and contacts
29 sites in 1 country.
29 sites in 1 country
United States29 sites
GSK Investigational Site
Albany, New York, 12208
GSK Investigational Site
Anchorage, Alaska, 99508
GSK Investigational Site
Asheville, North Carolina, 28816
GSK Investigational Site
Burbank, California, 91505
GSK Investigational Site
Chattanooga, Tennessee, 37403
GSK Investigational Site
Columbia, Missouri, 65212
GSK Investigational Site
Columbus, Ohio, 43214
GSK Investigational Site
Detroit, Michigan, 48201
GSK Investigational Site
Detroit, Michigan, 48202
GSK Investigational Site
Englewood, New Jersey, 07631
GSK Investigational Site
Fort Myers, Florida, 33908
GSK Investigational Site
Fort Worth, Texas, 76104
GSK Investigational Site
Jackson, Mississippi, 39216
GSK Investigational Site
Kansas City, Kansas, 66205
GSK Investigational Site
Kansas City, Missouri, 64132
GSK Investigational Site
Kingsport, Tennessee, 37660
GSK Investigational Site
Lebanon, New Hampshire, 03756
GSK Investigational Site
Los Angeles, California, 90095
GSK Investigational Site
Mesa, Arizona, 85284
GSK Investigational Site
Mobile, Alabama, 36604
GSK Investigational Site
Morristown, New Jersey, 07962-1956
GSK Investigational Site
Nashville, Tennessee, 37203
GSK Investigational Site
Oklahoma City, Oklahoma, 73104
GSK Investigational Site
Pittsburgh, Pennsylvania, 15224
GSK Investigational Site
Providence, Rhode Island, 02905
GSK Investigational Site
Rochester, New York, 14642
GSK Investigational Site
Seattle, Washington, 98109
GSK Investigational Site
St. Petersburg, Florida, 33705
GSK Investigational Site
Summit, New Jersey, 07962-1956
About this study
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
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
- Being tested
- Niraparib, Bevacizumab
- Keywords
- Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor, Ovarian Cancer, Primary Peritoneal carcinoma, Fallopian Tube, Vascular endothelial growth factor (VEGF) inhibitor, Bevacizumab, Niraparib
- Medical subject headings
- Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NiraparibDrug
Also called ZEJULA
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.
BevacizumabBiological
Also called Avastin
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Niraparib; Biological: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At 18 months
Secondary outcomes (21)
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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to end of treatment (70 months)
Number of Participants With TEAEs Leading to Niraparib Dose Reductions
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.
Measured: 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.
Measured: 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).
Measured: Baseline (Day 1) and end of treatment (70 months)
Change From Baseline (CFB) in Pulse Rate
Pulse Rate was 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).
Measured: Baseline (Day 1) and end of treatment (70 months)
Change From Baseline (CFB) in Temperature
Temperature was 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).
Measured: Baseline (Day 1) and end of treatment (70 months)
Number of Participants Who Used Concomitant Medications
Any permitted concomitant medication(s), including non-prescription medication(s) and herbal product(s), taken during the study were recorded.
Measured: Up to end of treatment (70 months)
Change From Baseline (CFB) in Hematology Parameters: Basophils, Eosinophil, Leukocytes, Platelets, Lymphocytes, Monocytes and Neutrophils
Blood samples were collected for the assessment of change from Baseline in hematology parameters. Baseline (Day 1) is defined as the most recent measurement prior to the first administration of study drug (including Cycle 1 Day 1).
Measured: Baseline (Day 1) and end of treatment (70 months)
Change From Baseline (CFB) in Hematology Parameter: Hemoglobin (Hb)
Blood samples were collected for the assessment of change from Baseline in hematology parameter. Baseline (Day 1) is defined as the most recent measurement prior to the first administration of study drug (including Cycle 1 Day 1).
Measured: Baseline (Day 1) and end of treatment (70 months)
Change From Baseline (CFB) in Hematology Parameter: Erythrocyte Mean Corpuscular Volume (MCV)
Blood samples were collected for the assessment of change from Baseline in hematology parameter. Baseline (Day 1) is defined as the most recent measurement prior to the first administration of study drug (including Cycle 1 Day 1).
Measured: Baseline (Day 1) and end of treatment (70 months)
Change From Baseline (CFB) in Clinical Chemistry Parameters: Urea Nitrogen, Glucose, Calcium, Chloride, Sodium, Magnesium and Potassium
Blood samples were collected for the assessment of change from Baseline in clinical chemistry parameters. Baseline (Day 1) is defined as the most recent measurement prior to the first administration of study drug (including Cycle 1 Day 1).
Measured: Baseline (Day 1) and end of treatment (70 months)
Change From Baseline (CFB) in Clinical Chemistry Parameters: Bilirubin and Creatinine
Blood samples were collected for the assessment of change from Baseline in clinical chemistry parameters. Baseline (Day 1) is defined as the most recent measurement prior to the first administration of study drug (including Cycle 1 Day 1).
Measured: Baseline (Day 1) and end of treatment (70 months)
Change From Baseline (CFB) in Clinical Chemistry Parameters: Albumin and Protein
Blood samples were collected for the assessment of change from baseline in clinical chemistry parameters. Baseline (Day 1) is defined as the most recent measurement prior to the first administration of study drug (including Cycle 1 Day 1).
Measured: Baseline (Day 1) and end of treatment (70 months)
Change From Baseline (CFB) in Clinical Chemistry Parameters: Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT)
Blood samples were collected for the assessment of change from baseline in clinical chemistry parameters. Baseline (Day 1) is defined as the most recent measurement prior to the first administration of study drug (including Cycle 1 Day 1).
Measured: Baseline (Day 1) and end of treatment (70 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2017
- Study start12 Dec 2017
- Primary completion24 Dec 2020
- Study completion12 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Ovarian NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tesaro, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03326193
- Sponsor's protocol ID
- 213358
- Other IDs
- 3000-02-004
- Status last verified
- Jul 2025
- First submitted
- 10 Oct 2017
- Last updated
- 31 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35690498Hardesty MM, Krivak TC, Wright GS, Hamilton E, Fleming EL, Belotte J, Gorman S, Compton N, Clements A, Gray HJ, Konecny GE, Moore RG, Richardson DL. A phase 2 trial of niraparib plus bevacizumab maintenance therapy following first-line platinum-based chemotherapy with bevacizumab in advanced ovarian cancer: final analysis and overall survival results from OVARIO. Gynecol Oncol. 2025 Aug;199:96-102. doi: 10.1016/j.ygyno.2025.06.014. Epub 2025 Jul 1.
PubMed 40602355Thaker PH, Areli Calderon Boyle T, Burns S, Lim J, Hartman J, Kalilani LV, Schilder JM, Hurteau JA, Golembesky AK. Characteristics and real-world outcomes of patients with epithelial ovarian cancer who received niraparib plus bevacizumab first-line maintenance therapy in the COMB1NE study. Int J Gynecol Cancer. 2024 Dec 2;34(12):1924-1931. doi: 10.1136/ijgc-2024-005611.
PubMed 39244209
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03326193
- Acronym / sponsor ID
- 213358
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 105 participants (actual)
- Lead sponsor
- Tesaro, Inc.Industry (pharma, biotech, devices)
- Study start
- 12 Dec 2017 (actual)
- Primary completion
- 24 Dec 2020 (actual)
- Study completion
- 12 Jul 2024 (actual)
- First posted
- 31 Oct 2017 (actual)
- Results
- Posted 19 Jan 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Participants receiving niraparib+ bevacizumab | Experimental | Drug: Niraparib, Biological: BevacizumabParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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.
Key exclusion criteria (15 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NiraparibAlso: ZEJULANiraparib 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. | Drug | Participants receiving niraparib+ bevacizumab |
| BevacizumabAlso: AvastinMaintenance 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. | Biological | Participants receiving niraparib+ bevacizumab |
Primary outcome
Progression Free Survival (PFS) Rate
Time frame: At 18 months
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.
21 secondary outcomes
Progression Free Survival (PFS) by RECIST v 1.1
Time frame: Up to end of study (approximately 79 months)
Overall Survival (OS)
Time frame: Up to end of study (approximately 79 months)
RECIST or Cancer Antigen (CA)-125 Progression Free Survival
Time frame: Up to end of study (approximately 79 months)
Change From Baseline (CFB) in Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI)
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)
Time frame: Up to end of study (approximately 79 months)
Time to Second Subsequent Therapy (TSST)
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)
Time frame: Up to end of treatment (70 months)
Number of Participants With TEAEs Leading to Niraparib Treatment Discontinuation
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)
Time frame: Up to end of treatment (70 months)
Change From Baseline (CFB) in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Time frame: Baseline (Day 1) and end of treatment (70 months)
Change From Baseline (CFB) in Pulse Rate
Time frame: Baseline (Day 1) and end of treatment (70 months)
Change From Baseline (CFB) in Temperature
Time frame: Baseline (Day 1) and end of treatment (70 months)
Number of Participants Who Used Concomitant Medications
Time frame: Up to end of treatment (70 months)
Change From Baseline (CFB) in Hematology Parameters: Basophils, Eosinophil, Leukocytes, Platelets, Lymphocytes, Monocytes and Neutrophils
Time frame: Baseline (Day 1) and end of treatment (70 months)
Change From Baseline (CFB) in Hematology Parameter: Hemoglobin (Hb)
Time frame: Baseline (Day 1) and end of treatment (70 months)
Change From Baseline (CFB) in Hematology Parameter: Erythrocyte Mean Corpuscular Volume (MCV)
Time frame: Baseline (Day 1) and end of treatment (70 months)
Change From Baseline (CFB) in Clinical Chemistry Parameters: Urea Nitrogen, Glucose, Calcium, Chloride, Sodium, Magnesium and Potassium
Time frame: Baseline (Day 1) and end of treatment (70 months)
Change From Baseline (CFB) in Clinical Chemistry Parameters: Bilirubin and Creatinine
Time frame: Baseline (Day 1) and end of treatment (70 months)
Change From Baseline (CFB) in Clinical Chemistry Parameters: Albumin and Protein
Time frame: Baseline (Day 1) and end of treatment (70 months)
Change From Baseline (CFB) in Clinical Chemistry Parameters: Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT)
Time frame: Baseline (Day 1) and end of treatment (70 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 35690498Hardesty 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.
- Derived from this study: PubMed 40602355Hardesty MM, Krivak TC, Wright GS, Hamilton E, Fleming EL, Belotte J, Gorman S, Compton N, Clements A, Gray HJ, Konecny GE, Moore RG, Richardson DL. A phase 2 trial of niraparib plus bevacizumab maintenance therapy following first-line platinum-based chemotherapy with bevacizumab in advanced ovarian cancer: final analysis and overall survival results from OVARIO. Gynecol Oncol. 2025 Aug;199:96-102. doi: 10.1016/j.ygyno.2025.06.014. Epub 2025 Jul 1.
- Derived from this study: PubMed 39244209Thaker PH, Areli Calderon Boyle T, Burns S, Lim J, Hartman J, Kalilani LV, Schilder JM, Hurteau JA, Golembesky AK. Characteristics and real-world outcomes of patients with epithelial ovarian cancer who received niraparib plus bevacizumab first-line maintenance therapy in the COMB1NE study. Int J Gynecol Cancer. 2024 Dec 2;34(12):1924-1931. doi: 10.1136/ijgc-2024-005611.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
29 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Niraparib and Bevacizumab in people with Ovarian Neoplasms, run by Tesaro, Inc. at 29 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) Rate (time frame: At 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03326193, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2025; AzTrials last refreshed its copy on 7 Nov 2026.