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

• Sponsor: Tesaro, Inc. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03326193
• Collaborator: (none)
• Enrollment: 105
• Locations: 28
• Arm: 1
• Anticipated Duration (Months): 59.2
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Neoplasms	Drug: Niraparib; Biological: Bevacizumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 105 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Masking Description: This is an open label study
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Dec 12, 2017
• Actual Primary Completion Date: Dec 24, 2020
• Anticipated Study Completion Date: Nov 18, 2022

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Participants receiving niraparib+ bevacizumab 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. 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; Niraparib will be administered orally once a day continuously throughout each 21 day cycle. 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.; Other Names: ZEJULA ; Biological: Bevacizumab; 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.; Other Names: Avastin

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) Rate [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.

Secondary Outcome Measures

1. Progression Free Survival by RECIST v 1.1 [Up to 3 years]

   Data is not reported as participants response is still ongoing at the time of primary analysis.

2. Overall Survival (OS) [Up to 3 years]

   Data is not reported as participants response is still ongoing at the time of primary analysis.

3. RECIST or Cancer Antigen (CA)-125 Progression Free Survival [Up to 3 years]

   Data is not reported as participants response is still ongoing at the time of primary analysis.

4. Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) [Baseline and up to 3 years]

   Data is not reported as participants response is still ongoing at the time of primary analysis.

5. Time to First Subsequent Therapy (TFST) [Up to 3 years]

   Data is not reported as participants response is still ongoing at the time of primary analysis.

6. Time to Second Subsequent Therapy (TSST) [Up to 3 years]

   Data is not reported as participants response is still ongoing at the time of primary analysis.

7. Number of Participants With Non-serious Treatment-emergent Adverse Events (TEAEs) [Up to a maximum of 33.68 months]

   TEAE is defined as any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with non-serious TEAEs with 5% threshold are reported.

8. Number of Participants With TEAEs Leading to Niraparib Treatment Discontinuation [Up to a maximum of 33.68 months]

   TEAE is defined as any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs leading to Niraparib treatment discontinuation are reported.

9. Number of Participants With TEAEs Leading to Niraparib Dose Reductions [Up to a maximum of 33.68 months]

   TEAE is defined as any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAES leading to Niraparib dose reductions are reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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 HRD or 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:

• 1. 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.
• 1. 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 ECOG score of 0 or 1.

• Participant must have normal blood pressure or well-controlled hypertension.

• Participant must agree to complete PROs (quality of life [QoL] 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 submitted for HRD testing during the Screening Period. 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 through180 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 (patients 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, breastfeeding, 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Mobile	Alabama	United States	36604
2	GSK Investigational Site	Anchorage	Alaska	United States	99508
3	GSK Investigational Site	Mesa	Arizona	United States	85284
4	GSK Investigational Site	Burbank	California	United States	91505
5	GSK Investigational Site	Los Angeles	California	United States	90095
6	GSK Investigational Site	Fort Myers	Florida	United States	33908
7	GSK Investigational Site	Saint Petersburg	Florida	United States	33705
8	GSK Investigational Site	Westwood	Kansas	United States	66205
9	GSK Investigational Site	Detroit	Michigan	United States	48201
10	GSK Investigational Site	Detroit	Michigan	United States	48202
11	GSK Investigational Site	Jackson	Mississippi	United States	39216
12	GSK Investigational Site	Columbia	Missouri	United States	65212
13	GSK Investigational Site	Kansas City	Missouri	United States	64132
14	GSK Investigational Site	Lebanon	New Hampshire	United States	03756
15	GSK Investigational Site	Englewood	New Jersey	United States	07631
16	GSK Investigational Site	Morristown	New Jersey	United States	07962-1956
17	GSK Investigational Site	Albany	New York	United States	12208
18	GSK Investigational Site	Rochester	New York	United States	14642
19	GSK Investigational Site	Asheville	North Carolina	United States	28816
20	GSK Investigational Site	Columbus	Ohio	United States	43214
21	GSK Investigational Site	Oklahoma City	Oklahoma	United States	73104
22	GSK Investigational Site	Pittsburgh	Pennsylvania	United States	15224
23	GSK Investigational Site	Providence	Rhode Island	United States	02905
24	GSK Investigational Site	Chattanooga	Tennessee	United States	37403
25	GSK Investigational Site	Kingsport	Tennessee	United States	37660
26	GSK Investigational Site	Nashville	Tennessee	United States	37203
27	GSK Investigational Site	Fort Worth	Texas	United States	76104
28	GSK Investigational Site	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Tesaro, Inc.

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - Dec 5, 2017
• Statistical Analysis Plan - Feb 9, 2021

More Information

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.

• Responsible Party: Tesaro, Inc.
• ClinicalTrials.gov Identifier: NCT03326193
• Other Study ID Numbers: 213358; 3000-02-004
• First Posted: Oct 31, 2017
• Last Update Posted: Jul 22, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Tesaro, Inc.: Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor; Ovarian Cancer; Primary Peritoneal carcinoma; Fallopian Tube; Vascular endothelial growth factor (VEGF) inhibitor; Bevacizumab; Niraparib
• Additional relevant MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Bevacizumab; Niraparib

Study Results

Participant Flow

Recruitment Details	The results presented are based on the primary analysis up to a maximum of 33.68 months. Data collection is still on-going and additional results will be provided after study completion.
Pre-assignment Detail	A total of 105 participants were enrolled in the study.

Arm/Group Title	Niraparib + Bevacizumab
Arm/Group Description	Participants received bevacizumab 15 milligram per kilogram (mg/kg) via a 30 minute intravenous (IV) infusion on Day 1 of each 21-day cycle. Niraparib (200 mg or 300 mg) was administered orally once a day continuously throughout each 21-day cycle. On Day 1 of each 21-day cycle, niraparib was administered upon completion of bevacizumab infusion.
Period Title: Overall Study
STARTED	105
COMPLETED	52
NOT COMPLETED	53

Baseline Characteristics

Arm/Group Title	Niraparib + Bevacizumab
Arm/Group Description	Participants received bevacizumab 15 milligram per kilogram (mg/kg) via a 30 minute intravenous (IV) infusion on Day 1 of each 21-day cycle. Niraparib (200 mg or 300 mg) was administered orally once a day continuously throughout each 21-day cycle. On Day 1 of each 21-day cycle, niraparib was administered upon completion of bevacizumab infusion.
Overall Participants	105
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	59.7 (10.33)
Sex: Female, Male (Count of Participants)
Female	105 100%
Male	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	91 86.7%
Black or African American	4 3.8%
Asian	3 2.9%
American Indian or Alaska Native	1 1%
Unknown	6 5.7%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS) Rate
Description	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

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) Population comprised of all participants who received any amount of niraparib (at least 1 dose).

Arm/Group Title	Niraparib + Bevacizumab
Arm/Group Description	Participants received bevacizumab 15 milligram per kilogram (mg/kg) via a 30 minute intravenous (IV) infusion on Day 1 of each 21-day cycle. Niraparib (200 mg or 300 mg) was administered orally once a day continuously throughout each 21-day cycle. On Day 1 of each 21-day cycle, niraparib was administered upon completion of bevacizumab infusion.
Measure Participants	105
Number (95% Confidence Interval) [Percentage of participants]	62 59%

2. Secondary Outcome

Title	Progression Free Survival by RECIST v 1.1
Description	Data is not reported as participants response is still ongoing at the time of primary analysis.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Overall Survival (OS)
Description	Data is not reported as participants response is still ongoing at the time of primary analysis.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	RECIST or Cancer Antigen (CA)-125 Progression Free Survival
Description	Data is not reported as participants response is still ongoing at the time of primary analysis.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI)
Description	Data is not reported as participants response is still ongoing at the time of primary analysis.
Time Frame	Baseline and up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Time to First Subsequent Therapy (TFST)
Description	Data is not reported as participants response is still ongoing at the time of primary analysis.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Time to Second Subsequent Therapy (TSST)
Description	Data is not reported as participants response is still ongoing at the time of primary analysis.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Number of Participants With Non-serious Treatment-emergent Adverse Events (TEAEs)
Description	TEAE is defined as any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with non-serious TEAEs with 5% threshold are reported.
Time Frame	Up to a maximum of 33.68 months

Outcome Measure Data

Analysis Population Description

Safety Population comprised of all participants who received any amount of study treatment (i.e. any amount of bevacizumab or niraparib during the study).

Arm/Group Title	Niraparib + Bevacizumab
Arm/Group Description	Participants received bevacizumab 15 milligram per kilogram (mg/kg) via a 30 minute intravenous (IV) infusion on Day 1 of each 21-day cycle. Niraparib (200 mg or 300 mg) was administered orally once a day continuously throughout each 21-day cycle. On Day 1 of each 21-day cycle, niraparib was administered upon completion of bevacizumab infusion.
Measure Participants	105
Count of Participants [Participants]	105 100%

9. Secondary Outcome

Title	Number of Participants With TEAEs Leading to Niraparib Treatment Discontinuation
Description	TEAE is defined as any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs leading to Niraparib treatment discontinuation are reported.
Time Frame	Up to a maximum of 33.68 months

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Niraparib + Bevacizumab
Arm/Group Description	Participants received bevacizumab 15 milligram per kilogram (mg/kg) via a 30 minute intravenous (IV) infusion on Day 1 of each 21-day cycle. Niraparib (200 mg or 300 mg) was administered orally once a day continuously throughout each 21-day cycle. On Day 1 of each 21-day cycle, niraparib was administered upon completion of bevacizumab infusion.
Measure Participants	105
Count of Participants [Participants]	30 28.6%

10. Secondary Outcome

Title	Number of Participants With TEAEs Leading to Niraparib Dose Reductions
Description	TEAE is defined as any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAES leading to Niraparib dose reductions are reported.
Time Frame	Up to a maximum of 33.68 months

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Niraparib + Bevacizumab
Arm/Group Description	Participants received bevacizumab 15 milligram per kilogram (mg/kg) via a 30 minute intravenous (IV) infusion on Day 1 of each 21-day cycle. Niraparib (200 mg or 300 mg) was administered orally once a day continuously throughout each 21-day cycle. On Day 1 of each 21-day cycle, niraparib was administered upon completion of bevacizumab infusion.
Measure Participants	105
Count of Participants [Participants]	81 77.1%

Adverse Events

Time Frame	Treatment emergent non-serious adverse events and serious adverse events were collected up to a maximum of 33.68 months
Adverse Event Reporting Description	Safety Population comprised of participants who received any amount of study treatment (i.e., any amount of bevacizumab or niraparib during the study). The results presented are based on the primary analysis up to a maximum of 33.68 months. Data collection is still on-going and additional results will be provided after study completion.
Arm/Group Title	Niraparib + Bevacizumab
Arm/Group Description	Participants received bevacizumab 15 milligram per kilogram (mg/kg) via a 30 minute intravenous (IV) infusion on Day 1 of each 21-day cycle. Niraparib (200 mg or 300 mg) was administered orally once a day continuously throughout each 21-day cycle. On Day 1 of each 21-day cycle, niraparib was administered upon completion of bevacizumab infusion.
All Cause Mortality
	Niraparib + Bevacizumab
	Affected / at Risk (%)	# Events
Total	19/105 (18.1%)
Serious Adverse Events
	Niraparib + Bevacizumab
	Affected / at Risk (%)	# Events
Total	32/105 (30.5%)
Blood and lymphatic system disorders
Thrombocytopenia	6/105 (5.7%)
Anaemia	1/105 (1%)
Pancytopenia	1/105 (1%)
Cardiac disorders
Acute coronary syndrome	1/105 (1%)
Gastrointestinal disorders
Small intestinal obstruction	2/105 (1.9%)
Dysphagia	1/105 (1%)
Lower gastrointestinal haemorrhage	1/105 (1%)
General disorders
Chest pain	2/105 (1.9%)
Pyrexia	1/105 (1%)
Infections and infestations
Appendicitis	1/105 (1%)
Clostridium difficile colitis	1/105 (1%)
Sepsis	1/105 (1%)
Skin infection	1/105 (1%)
Injury, poisoning and procedural complications
Spinal fracture	1/105 (1%)
Investigations
Platelet count decreased	8/105 (7.6%)
Metabolism and nutrition disorders
Fluid overload	1/105 (1%)
Hyponatraemia	1/105 (1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	1/105 (1%)
Nervous system disorders
Headache	1/105 (1%)
Neuropathy peripheral	1/105 (1%)
Posterior reversible encephalopathy syndrome	1/105 (1%)
Psychiatric disorders
Bipolar disorder	1/105 (1%)
Psychotic disorder	1/105 (1%)
Reproductive system and breast disorders
Vaginal haemorrhage	1/105 (1%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/105 (1%)
Vascular disorders
Hypertension	2/105 (1.9%)
Other (Not Including Serious) Adverse Events
	Niraparib + Bevacizumab
	Affected / at Risk (%)	# Events
Total	105/105 (100%)
Blood and lymphatic system disorders
Anaemia	56/105 (53.3%)
Thrombocytopenia	37/105 (35.2%)
Neutropenia	15/105 (14.3%)
Leukopenia	7/105 (6.7%)
Cardiac disorders
Palpitations	12/105 (11.4%)
Tachycardia	10/105 (9.5%)
Ear and labyrinth disorders
Tinnitus	6/105 (5.7%)
Endocrine disorders
Endocrine disorders	6/105 (5.7%)
Eye disorders
Vision blurred	7/105 (6.7%)
Gastrointestinal disorders
Nausea	63/105 (60%)
Constipation	39/105 (37.1%)
Abdominal pain	32/105 (30.5%)
Vomiting	32/105 (30.5%)
Diarrhoea	27/105 (25.7%)
Stomatitis	20/105 (19%)
Abdominal distension	13/105 (12.4%)
Gastrooesophageal reflux disease	8/105 (7.6%)
Dry mouth	7/105 (6.7%)
Abdominal pain upper	6/105 (5.7%)
Dyspepsia	6/105 (5.7%)
General disorders
Fatigue	72/105 (68.6%)
Oedema peripheral	15/105 (14.3%)
Asthenia	10/105 (9.5%)
Chills	6/105 (5.7%)
Pain	6/105 (5.7%)
Pyrexia	6/105 (5.7%)
Immune system disorders
Immune system disorders	10/105 (9.5%)
Infections and infestations
Urinary tract infection	27/105 (25.7%)
Upper respiratory tract infection	13/105 (12.4%)
Nasopharyngitis	8/105 (7.6%)
Sinusitis	7/105 (6.7%)
Skin infection	6/105 (5.7%)
Injury, poisoning and procedural complications
Contusion	8/105 (7.6%)
Fall	6/105 (5.7%)
Investigations
Platelet count decreased	42/105 (40%)
White blood cell count decreased	21/105 (20%)
Neutrophil count decreased	17/105 (16.2%)
Activated partial thromboplastin time prolonged	13/105 (12.4%)
Blood creatinine increased	11/105 (10.5%)
Alanine aminotransferase increased	8/105 (7.6%)
Aspartate aminotransferase increased	7/105 (6.7%)
Weight increased	7/105 (6.7%)
Metabolism and nutrition disorders
Decreased appetite	17/105 (16.2%)
Hypomagnesaemia	14/105 (13.3%)
Dehydration	10/105 (9.5%)
Hyperglycaemia	9/105 (8.6%)
Hypokalaemia	9/105 (8.6%)
Hyponatraemia	9/105 (8.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	32/105 (30.5%)
Pain in extremity	21/105 (20%)
Back pain	18/105 (17.1%)
Myalgia	16/105 (15.2%)
Muscle spasms	14/105 (13.3%)
Muscular weakness	11/105 (10.5%)
Neck pain	11/105 (10.5%)
Musculoskeletal pain	9/105 (8.6%)
Bone pain	7/105 (6.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)	6/105 (5.7%)
Nervous system disorders
Headache	56/105 (53.3%)
Dizziness	30/105 (28.6%)
Neuropathy peripheral	14/105 (13.3%)
Peripheral sensory neuropathy	10/105 (9.5%)
Memory impairment	7/105 (6.7%)
Dysgeusia	6/105 (5.7%)
Psychiatric disorders
Insomnia	19/105 (18.1%)
Anxiety	11/105 (10.5%)
Depression	9/105 (8.6%)
Renal and urinary disorders
Proteinuria	43/105 (41%)
Haematuria	9/105 (8.6%)
Pollakiuria	7/105 (6.7%)
Reproductive system and breast disorders
Reproductive system and breast disorders	16/105 (15.2%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	34/105 (32.4%)
Epistaxis	28/105 (26.7%)
Cough	23/105 (21.9%)
Oropharyngeal pain	11/105 (10.5%)
Nasal congestion	10/105 (9.5%)
Skin and subcutaneous tissue disorders
Rash	11/105 (10.5%)
Dry skin	6/105 (5.7%)
Hyperhidrosis	6/105 (5.7%)
Pruritus	6/105 (5.7%)
Vascular disorders
Hypertension	57/105 (54.3%)
Hot flush	14/105 (13.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.