Japan Phase 2 Study of Niraparib in Participants With Advanced, Relapsed Ovarian Cancer

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03759600
• Collaborator: (none)
• Enrollment: 20
• Locations: 33
• Arm: 1
• Actual Duration (Months): 17.4
• Patients Per Site: 0.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of niraparib in participants with advanced, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received 3 or 4 previous chemotherapy regimens.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer	Drug: Niraparib	Phase 2

Detailed Description

The drug being tested in this study is called niraparib. Niraparib is being tested to treat people who have the homologous recombination deficiency (HRD)-positive, advanced, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer. This study will look at the efficacy and safety of niraparib in Japanese participants.

The study will enroll approximately 16 participants. Participants will be enrolled to one group and after that will be asked to take niraparib capsules at the same time each day throughout the study:

• Niraparib 300 mg

This multi-center trial will be conducted in Japan. The overall time to participate in this study is approximately 23 months. Participants will make multiple visits to the clinic in the treatment period, and the post-treatment period including follow-up assessments after the last dose of the study drug.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multicenter, Open-label, Single-arm Study to Evaluate the Safety and Efficacy of Niraparib in Japanese Patients With Advanced, Relapsed, High-grade Serous Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Have Received 3 or 4 Previous Chemotherapy Regimens
• Actual Study Start Date: Dec 26, 2018
• Actual Primary Completion Date: Jul 1, 2019
• Actual Study Completion Date: Jun 9, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Niraparib 300 mg Niraparib 300 milligrams (mg), capsules, orally, once daily on Days 1 - 28 of each 28-day treatment cycle up to 6 cycles till data cut-off: 01 July 2019.	Drug: Niraparib; Niraparib capsule

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) [Until disease progression, death or data cut-off (Up to approximately 5 months)]

   ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) as assessed by the Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as disappearance of all target lesions and PR was defined as at least a 30% decrease in sum of diameters (SoD) of target lesions, taking as a reference the Baseline SoD.

Secondary Outcome Measures

1. Duration of Response (DOR) [Until disease progression, death or data cut-off (Up to approximately 5 months)]

   DOR was defined as the time from the first documented CR or PR per RECIST v. 1.1 to disease recurrence or objective disease progression whichever occurs first. CR was defined as disappearance of all target lesions and PR was defined as at least a 30% decrease in sum of diameters (SoD) of target lesions, taking as a reference the Baseline SoD.

2. Disease Control Rate (DCR) [Until disease progression, death or data cut-off (Up to approximately 5 months)]

   DCR was defined as the percentage of participants achieving CR, PR or Stable Disease (SD) as assessed by the Investigator per RECIST v. 1.1. CR was defined as disappearance of all target lesions and PR was defined as at least a 30% decrease in sum of diameters (SoD) of target lesions, taking as a reference the Baseline SoD. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD was defined as at least a 20% increase in the SoD of target lesions, taking as a reference the smallest (nadir) SoD since (and including) Baseline.

3. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Up to 30 days after the last dose (Approximately 6 months)]

   An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) was defined as an adverse event with an onset that occurs after receiving study drug.

4. Number of Participants With Grade 3 or Higher TEAEs [Up to 30 days after the last dose (Approximately 6 months)]

   An AE was defined as any untoward medical occurrence in a participant who has enrolled in a study; it does not necessarily have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) was defined as an adverse event with an onset that occurs after receiving study drug. A severity grade was defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03. As per NCI-CTCAE, Grade 1 scales as Mild; Grade 2 scales as Moderate; Grade 3 scales as severe or medically significant but not immediately life threatening; Grade 4 scales as life-threatening consequences; and Grade 5 scales as death related to AE.

5. Number of Participants With Serious TEAEs [Up to 30 days after the last dose (Approximately 6 months)]

   An AE was defined as any untoward medical occurrence in a participant who has enrolled in a study; it does not necessarily have a causal relationship with this treatment. An SAE was any AE that results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. TEAE was defined as an adverse event with an onset that occurs after receiving study drug.

6. Number of Participants With TEAEs Leading to Drug Discontinuation [Up to 30 days after the last dose (Approximately 6 months)]

   An AE was defined as any untoward medical occurrence in a participant who has enrolled in a study; it does not necessarily have a causal relationship with this treatment. A TEAE was defined as an adverse event with an onset that occurs after receiving study drug.

7. Number of Participants With TEAEs Leading to Dose Interruption [Up to 30 days after the last dose (Approximately 6 months)]

   An AE was defined as any untoward medical occurrence in a participant who has enrolled in a study; it does not necessarily have a causal relationship with this treatment. A TEAE was defined as an adverse event with an onset that occurs after receiving study drug.

8. Number of Participants With TEAEs Leading to Dose Reduction [Up to 30 days after the last dose (Approximately 6 months)]

   An AE was defined as any untoward medical occurrence in a participant who has enrolled in a study; it does not necessarily have a causal relationship with this treatment. A TEAE was defined as an adverse event with an onset that occurs after receiving study drug.

9. Progression Free Survival (PFS) [Until disease progression, death or data cut-off (Up to approximately 5 months)]

   PFS was defined as the time in months from the date of first study drug administration to the date of first documentation of progressive disease (PD) or death as assessed by the RECIST version 1.1. Per RECIST 1.1, PD was defined as at least a 20% increase in the SoD (Sum of Diameters) of target lesions, taking as a reference the smallest (nadir) SoD since (and including) Baseline.

10. Overall Survival (OS) [Up to data cut-off approximately 6 months]

    OS was defined as the time in months from the study enrollment to death due to any cause.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria

1. Japanese female participants aged 20 years or older on the day of signing informed consent.

2. Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.

3. Participants must agree to undergo tumor homologous recombination deficiency/deficient (HRD) testing, and this test result must show that participants have an HRD-positive tumor (defined by the presence of a deleterious or suspected deleterious breast cancer gene (BRCA) mutation or be positive for genomic instability) by the central laboratory selected by the sponsor.

Note 1: The study HRD test result must be received prior to enrollment. The tumor sample may be submitted for HRD testing prior to the screening period (ie, within 40 days before Cycle 1 Day 1) if the consent has been obtained and it appears the participant is likely to meet other eligibility requirements.

Note 2: If historic blood germline BRCA mutation (gBRCAmut) is detected by a prior gBRCAmut testing, then tumor HRD sample test results are not required prior to enrollment; however, HRD testing still needs to be performed.

1. Participants must have histologically diagnosed, relapsed, high-grade (Grade 2 or 3) serous epithelial ovarian, fallopian tube, or primary peritoneal cancer with recurrent disease and must have been previously treated with chemotherapy and have not experienced disease progression at least 6 months to the last chemotherapy containing platinum-based anticancer agents.

2. Participants must have completed 3 or 4 previous chemotherapy regimens. Participants must have completed their last chemotherapy regimen >4 weeks prior to treatment initiation.

3. Participants must have at least one measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) (v.1.1).

4. Participants must have performance status of ≤1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale.

5. Participants must have adequate organ function as indicated by the following laboratory values:

• Absolute neutrophil count (ANC) ≥1,500/μL.

• Platelet count ≥150,000/μL.

• Hemoglobin ≥10 g/dL.

• Serum creatinine ≤1.5× institutional upper limit of normal (ULN) OR calculated creatinine clearance ≥50 mL/minute, using the Cockcroft-Gault equation.

• Total bilirubin ≤1.5×ULN OR direct bilirubin ≤1×ULN.

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN unless liver metastases were present, in which case they had to be ≤5×ULN.

1. Participants must have formalin-fixed, paraffin-embedded tumor samples available from the primary or recurrent cancer or agree to undergo fresh biopsy prior to study treatment initiation.

2. Participants must be able to take oral medications.

3. Female participants of childbearing potential must be negative for pregnancy test (beta-human chorionic gonadotropin [β-hCG]) within 7 days prior to receiving the first dose of study treatment.

4. Female participants who:

• Are postmenopausal for at least 1 year before the screening visit, OR

• Are surgically sterile, OR

• If they are of childbearing potential, agree to practice 1 highly effective method of contraception and 1 additional effective (barrier) method at the same time, from the time of signing the informed consent through 180 days after the last dose of study drug, OR

• Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods], condoms only, withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)

Exclusion Criteria

1. Participants who have had palliative radiotherapy encompassing >20% of the bone marrow within 1 week of the first dose of study treatment.

2. Participants who have any known, persistent (>4 weeks), Grade ≥3 hematologic toxicity from last cancer therapy.

3. Participants who have any known, persistent (>4 weeks), Grade ≥3 fatigue during the last cancer therapy.

4. Participants who have received pelvic radiotherapy as treatment for primary or recurrent disease within 1 year of the first dose of study treatment.

5. Participants who have symptomatic, uncontrolled brain or leptomeningeal metastases.

To be considered "controlled," central nervous system (CNS) disease must have undergone treatment (eg, radiation or chemotherapy) at least 1 month prior to study enrollment. The participant must not have had any new or progressive signs or symptoms related to the CNS disease and must have been taking a stable dose of steroids or no steroids (as long as these were started at least 4 weeks prior to enrollment] or no steroids). A scan to confirm the absence of brain metastases at baseline was not required. Participants with spinal cord compression might have been considered if they had received definitive treatment for this and evidence of clinically stable disease for 28 days.

1. Participants who have known hypersensitivity to the components of niraparib.

2. Participants who have had prior treatment with a known poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors.

3. Participant who have had treatment with any investigational products within 28 days or 5 half-lives (whichever was longer) before the first dose.

4. Participants who have had major surgery per Investigator judgment within 3 weeks of the first dose. Participant must have recovered from any effects of any major surgery.

5. Participants who have diagnosis, detection, or treatment of invasive second primary malignancy other than ovarian cancer ≤24 months prior to study enrollment (except basal or squamous cell carcinoma of the skin that was definitively treated). Note: Participants must not have any known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), irrespective of the time for disease history.

6. Participants who are considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days of the first dose) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, small bowel obstruction or other serious gastrointestinal disorder, or any psychiatric disorder that prohibits obtaining informed consent.

7. Participants who have received a transfusion (platelets or red blood cells) within 4 weeks of the first dose of study treatment.

8. Participants who have received a live virus or bacterial vaccines within 4 weeks of the first dose of study treatment.

9. Participants who have a history or current evidence of any condition, therapy, or lab abnormality (including active or uncontrolled myelosuppression [ie, anemia, leukopenia, neutropenia, thrombocytopenia]) that might confound the results of the study, interfere with the participant's participation throughout the study period, or study participation is not in the best interest of the participant.

10. Participants who are regular user (including "recreational use") of any illicit drugs at the time of signing informed consent or have a recent history (within the past year) of drug or alcohol abuse.

11. Participants who are pregnant or breast-feeding or expecting to conceive within the planned duration of the study.

NOTE: If a breast-feeding woman discontinue breast-feeding, she may be enrolled in the study.

1. Participants who are immunocompromised (participants with splenectomy are allowed).

2. Participants who have known human immunodeficiency virus (HIV) positive.

3. Participants who have known hepatitis B surface antigen (HBsAg) positive, or known or suspected active hepatitis C virus (HCV) infection.

NOTE: Participants who are positive for hepatitis B core antibody (HBcAb) or hepatitis B surface antibody (HBsAb) can be enrolled but must have an undetectable hepatitis B virus (HBV) viral load. Participants who have positive hepatitis C virus antibody (HCVAb) must have an undetectable HCV viral load.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aichi Cancer Center Hospital	Nagoya	Aichi	Japan
2	Hirosaki University Hospital	Hirosaki	Aomori	Japan
3	National Cancer Center Hospital East	Kashiwa	Chiba	Japan
4	The Jikei University Kashiwa Hospital	Kashiwa	Chiba	Japan
5	Shikoku Cancer Center	Matsuyama	Ehime	Japan
6	Ehime University Hospital	Toon	Ehime	Japan
7	Kurume University Hospital	Kurume	Fukuoka	Japan
8	Kure Medical Center and Chugoku Cancer Center	Kure	Hiroshima	Japan
9	Hokkaido University Hospital	Sapporo	Hokkaido	Japan
10	Sapporo Medical University Hospital	Sapporo	Hokkaido	Japan
11	Hyogo Cancer Center	Akashi	Hyogo	Japan
12	Kansai Rosai Hospital	Amagasaki	Hyogo	Japan
13	Iwate Medical University Hospital	Morioka	Iwate	Japan
14	Tokai University Hospital	Isehara	Kanagawa	Japan
15	Nippon Medical School Musashi Kosugi Hospital	Kawasaki	Kanagawa	Japan
16	Mie University Hospital	Tsu	Mie	Japan
17	Tohoku University Hospital	Sendai	Miyagi	Japan
18	University of the Ryukyus Hospital	Nakagami-gun	Okinawa	Japan
19	Kindai University Hospital	Osakasayama	Osaka	Japan
20	Saitama Medical University International Medical Center	Hidaka	Saitama	Japan
21	Shizuoka Cancer Center	Nagaizumi-cho	Shizuoka	Japan
22	National Cancer Center Hospital	Chuo-ku	Tokyo	Japan
23	Cancer Institute Hospital	Koto-ku	Tokyo	Japan
24	The Jikei University Hospital	Minato-ku	Tokyo	Japan
25	Toho University Omori Medical Center	Ota-ku	Tokyo	Japan
26	Keio University Hospital	Shinjuku-ku	Tokyo	Japan
27	Chiba Cancer Center	Chiba		Japan
28	Chiba University Hospital	Chiba		Japan
29	Gifu University Hospital	Gifu		Japan
30	Kagoshima City Hospital	Kagoshima		Japan
31	Kyoto University Hospital	Kyoto		Japan
32	Nagasaki University Hospital	Nagasaki		Japan
33	Niigata University Medical & Dental Hospital	Niigata		Japan

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

• Study Protocol - Jan 18, 2019
• Statistical Analysis Plan - Aug 8, 2019

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT03759600
• Other Study ID Numbers: Niraparib-2002; U1111-1222-4100; JapicCTI-184224
• First Posted: Nov 30, 2018
• Last Update Posted: Aug 11, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Niraparib

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 17 investigative sites in Japan from 26 December 2018 to data cut-off: 01 July 2019.
Pre-assignment Detail	Female participants with a diagnosis of advanced, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received 3 or 4 prior lines of anti-cancer therapy and are platinum-sensitive to the last platinum-based therapy were enrolled to receive niraparib 300 mg in this study.

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Niraparib 300 milligrams (mg), capsules, orally, once daily on Days 1-28 of each 28-day treatment cycle up to 6 cycles till data cut-off: 01 July 2019.
Period Title: Overall Study
STARTED	20
COMPLETED	0
NOT COMPLETED	20

Baseline Characteristics

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Niraparib 300 milligrams (mg), capsules, orally, once daily on Days 1-28 of each 28-day treatment cycle up to 6 cycles till data cut-off: 01 July 2019.
Overall Participants	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.4 (10.69)
Sex: Female, Male (Count of Participants)
Female	20 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	20 100%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
Japan	20 100%
Time from First Diagnosis to First Dose (years) [Median (Full Range) ]
Median (Full Range) [years]	4.71
Primary Tumor Site (Count of Participants)
Ovarian	13 65%
Primary Peritoneal	5 25%
Fallopian Tube	2 10%
Cancer Stage (FIGO) at Time of Initial Diagnosis (Count of Participants)
IA	1 5%
IC	1 5%
IIB	1 5%
IIC	1 5%
IIIA	1 5%
IIIC	12 60%
IV	3 15%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	155.5 (6.57)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	53.70 (9.701)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	22.23 (3.936)
Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants)
0	15 75%
1	5 25%
Number of Prior Lines of Chemotherapy (Count of Participants)
3	12 60%
4	8 40%
Prior Taxane (Count of Participants)
Participants Who Received Taxane	20 100%
Prior Bevacizumab (Count of Participants)
Participants Who Received Bevacizumab	10 50%
Participants Who Did Not Received Bevacizumab	10 50%
Prior Doxorubicin (Count of Participants)
Participants Who Received Doxorubicin	9 45%
Participants Who Did Not Received Doxorubicin	11 55%
Prior Liposomal Doxorubicin (Count of Participants)
Who Did Not Received Liposomal Doxorubicin	20 100%
Prior Gemcitabine (Count of Participants)
Participants Who Received Gemcitabine	11 55%
Participants Who Did Not Received Gemcitabine	9 45%
Duration between the End Date of the Last Chemotherapy Regimen and the First Dose of Study Treatment (months) [Median (Full Range) ]
Median (Full Range) [months]	2.1
Duration between End Date of the Last Platinum-based Therapy and the First Dose of Study Treatment (months) [Median (Full Range) ]
Median (Full Range) [months]	16.3
Prior Surgery/Procedure for Study Indication (Count of Participants)
Participants Who Had Prior Surgery	20 100%
Number of Prior Surgery/Procedure for Study Indication (surgery) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [surgery]	2.3 (1.34)
Prior Radiation Therapy Related to the Study Indication (Count of Participants)
Had Radiation Therapy	2 10%
Had No Radiation Therapy	18 90%
Response to Last Platinum-based Therapy (Count of Participants)
Complete Response (CR)	9 45%
Partial Response (PR)	8 40%
Stable Disease (SD)	2 10%
Unknown	1 5%
Time to Progression after the Last Platinum Therapy (Count of Participants)
6-12 Month	12 60%
More Than 12 Month	8 40%
Ovarian Cancer Pathology Histological: Histologic Subtype (Count of Participants)
Serous	20 100%
Endometrioid	0 0%
Mucinous	0 0%
Other	0 0%
Ovarian Cancer Pathology Histological: Tumor Grade (Count of Participants)
Grade 2	1 5%
Grade 3	6 30%
High Grade	13 65%
Germline Breast Cancer (Gene) (BRCA1) Mutant (Count of Participants)
Without Mutant	3 15%
Unknown	17 85%
Germline BRCA2 Mutant (Count of Participants)
Without Mutant	3 15%
Unknown	17 85%
Homologous Recombination Deficiency/Deficient (HRD) CDx Test Result (Count of Participants)
Positive	20 100%
Genomic Instability Status (Count of Participants)
Positive	17 85%
Unknown	3 15%
Tumor BRCA1/BRCA2 Mutation Status (Count of Participants)
Negative	6 30%
Positive	13 65%
Unknown	1 5%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR)
Description	ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) as assessed by the Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as disappearance of all target lesions and PR was defined as at least a 30% decrease in sum of diameters (SoD) of target lesions, taking as a reference the Baseline SoD.
Time Frame	Until disease progression, death or data cut-off (Up to approximately 5 months)

Outcome Measure Data

Analysis Population Description

FAS included all participants who received at least 1 dose of study drug and have measurable disease at Baseline.

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Niraparib 300 milligrams (mg), capsules, orally, once daily on Days 1-28 of each 28-day treatment cycle up to 6 cycles till data cut-off: 01 July 2019.
Measure Participants	20
Number [percentage of participants]	35.0 175%

2. Secondary Outcome

Title	Duration of Response (DOR)
Description	DOR was defined as the time from the first documented CR or PR per RECIST v. 1.1 to disease recurrence or objective disease progression whichever occurs first. CR was defined as disappearance of all target lesions and PR was defined as at least a 30% decrease in sum of diameters (SoD) of target lesions, taking as a reference the Baseline SoD.
Time Frame	Until disease progression, death or data cut-off (Up to approximately 5 months)

Outcome Measure Data

Analysis Population Description

FAS included all participants who received at least 1 dose of study drug and have measurable disease at Baseline. Only Responders were analyzed for this outcome measure.

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Niraparib 300 milligrams (mg), capsules, orally, once daily on Days 1-28 of each 28-day treatment cycle up to 6 cycles till data cut-off: 01 July 2019.
Measure Participants	7
Median (95% Confidence Interval) [months]	NA

3. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	DCR was defined as the percentage of participants achieving CR, PR or Stable Disease (SD) as assessed by the Investigator per RECIST v. 1.1. CR was defined as disappearance of all target lesions and PR was defined as at least a 30% decrease in sum of diameters (SoD) of target lesions, taking as a reference the Baseline SoD. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD was defined as at least a 20% increase in the SoD of target lesions, taking as a reference the smallest (nadir) SoD since (and including) Baseline.
Time Frame	Until disease progression, death or data cut-off (Up to approximately 5 months)

Outcome Measure Data

Analysis Population Description

FAS included all participants who received at least 1 dose of study drug and have measurable disease at Baseline.

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Niraparib 300 milligrams (mg), capsules, orally, once daily on Days 1-28 of each 28-day treatment cycle up to 6 cycles till data cut-off: 01 July 2019.
Measure Participants	20
Number (95% Confidence Interval) [percentage of participants]	90.0 450%

4. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description	An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) was defined as an adverse event with an onset that occurs after receiving study drug.
Time Frame	Up to 30 days after the last dose (Approximately 6 months)

Outcome Measure Data

Analysis Population Description

Safety Analysis Set included participant who received at least 1 dose of study drug.

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Niraparib 300 milligrams (mg), capsules, orally, once daily on Days 1-28 of each 28-day treatment cycle up to 6 cycles till data cut-off: 01 July 2019.
Measure Participants	20
Count of Participants [Participants]	20 100%

5. Secondary Outcome

Title	Number of Participants With Grade 3 or Higher TEAEs
Description	An AE was defined as any untoward medical occurrence in a participant who has enrolled in a study; it does not necessarily have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) was defined as an adverse event with an onset that occurs after receiving study drug. A severity grade was defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03. As per NCI-CTCAE, Grade 1 scales as Mild; Grade 2 scales as Moderate; Grade 3 scales as severe or medically significant but not immediately life threatening; Grade 4 scales as life-threatening consequences; and Grade 5 scales as death related to AE.
Time Frame	Up to 30 days after the last dose (Approximately 6 months)

Outcome Measure Data

Analysis Population Description

Safety Analysis Set included participant who received at least 1 dose of study drug.

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Niraparib 300 milligrams (mg), capsules, orally, once daily on Days 1-28 of each 28-day treatment cycle up to 6 cycles till data cut-off: 01 July 2019.
Measure Participants	20
Count of Participants [Participants]	15 75%

6. Secondary Outcome

Title	Number of Participants With Serious TEAEs
Description	An AE was defined as any untoward medical occurrence in a participant who has enrolled in a study; it does not necessarily have a causal relationship with this treatment. An SAE was any AE that results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. TEAE was defined as an adverse event with an onset that occurs after receiving study drug.
Time Frame	Up to 30 days after the last dose (Approximately 6 months)

Outcome Measure Data

Analysis Population Description

Safety Analysis Set included participant who received at least 1 dose of study drug.

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Niraparib 300 milligrams (mg), capsules, orally, once daily on Days 1-28 of each 28-day treatment cycle up to 6 cycles till data cut-off: 01 July 2019.
Measure Participants	20
Count of Participants [Participants]	4 20%

7. Secondary Outcome

Title	Number of Participants With TEAEs Leading to Drug Discontinuation
Description	An AE was defined as any untoward medical occurrence in a participant who has enrolled in a study; it does not necessarily have a causal relationship with this treatment. A TEAE was defined as an adverse event with an onset that occurs after receiving study drug.
Time Frame	Up to 30 days after the last dose (Approximately 6 months)

Outcome Measure Data

Analysis Population Description

Safety Analysis Set included participant who received at least 1 dose of study drug.

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Niraparib 300 milligrams (mg), capsules, orally, once daily on Days 1-28 of each 28-day treatment cycle up to 6 cycles till data cut-off: 01 July 2019.
Measure Participants	20
Count of Participants [Participants]	1 5%

8. Secondary Outcome

Title	Number of Participants With TEAEs Leading to Dose Interruption
Description	An AE was defined as any untoward medical occurrence in a participant who has enrolled in a study; it does not necessarily have a causal relationship with this treatment. A TEAE was defined as an adverse event with an onset that occurs after receiving study drug.
Time Frame	Up to 30 days after the last dose (Approximately 6 months)

Outcome Measure Data

Analysis Population Description

Safety Analysis Set included participant who received at least 1 dose of study drug.

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Niraparib 300 milligrams (mg), capsules, orally, once daily on Days 1-28 of each 28-day treatment cycle up to 6 cycles till data cut-off: 01 July 2019.
Measure Participants	20
Count of Participants [Participants]	15 75%

9. Secondary Outcome

Title	Number of Participants With TEAEs Leading to Dose Reduction
Description	An AE was defined as any untoward medical occurrence in a participant who has enrolled in a study; it does not necessarily have a causal relationship with this treatment. A TEAE was defined as an adverse event with an onset that occurs after receiving study drug.
Time Frame	Up to 30 days after the last dose (Approximately 6 months)

Outcome Measure Data

Analysis Population Description

Safety Analysis Set included participant who received at least 1 dose of study drug.

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Niraparib 300 milligrams (mg), capsules, orally, once daily on Days 1-28 of each 28-day treatment cycle up to 6 cycles till data cut-off: 01 July 2019.
Measure Participants	20
Count of Participants [Participants]	14 70%

10. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS was defined as the time in months from the date of first study drug administration to the date of first documentation of progressive disease (PD) or death as assessed by the RECIST version 1.1. Per RECIST 1.1, PD was defined as at least a 20% increase in the SoD (Sum of Diameters) of target lesions, taking as a reference the smallest (nadir) SoD since (and including) Baseline.
Time Frame	Until disease progression, death or data cut-off (Up to approximately 5 months)

Outcome Measure Data

Analysis Population Description

FAS included all participants who received at least 1 dose of study drug and have measurable disease at Baseline.

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Niraparib 300 milligrams (mg), capsules, orally, once daily on Days 1-28 of each 28-day treatment cycle up to 6 cycles till data cut-off: 01 July 2019.
Measure Participants	20
Median (95% Confidence Interval) [months]	4.3

11. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time in months from the study enrollment to death due to any cause.
Time Frame	Up to data cut-off approximately 6 months

Outcome Measure Data

Analysis Population Description

FAS included all participants who received at least 1 dose of study drug and have measurable disease at Baseline.

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Niraparib 300 milligrams (mg), capsules, orally, once daily on Days 1-28 of each 28-day treatment cycle up to 6 cycles till data cut-off: 01 July 2019.
Measure Participants	20
Median (95% Confidence Interval) [months]	NA

Adverse Events

Time Frame	Up to 30 days after the last dose (Approximately 6 months)
Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Niraparib 300 milligrams (mg), capsules, orally, once daily on Days 1-28 of each 28-day treatment cycle up to 6 cycles till data cut-off: 01 July 2019.
All Cause Mortality
	Niraparib 300 mg
	Affected / at Risk (%)	# Events
Total	0/20 (0%)
Serious Adverse Events
	Niraparib 300 mg
	Affected / at Risk (%)	# Events
Total	4/20 (20%)
Blood and lymphatic system disorders
Anaemia	2/20 (10%)
Gastrointestinal disorders
Ascites	1/20 (5%)
Investigations
Platelet count decreased	2/20 (10%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/20 (5%)
Other (Not Including Serious) Adverse Events
	Niraparib 300 mg
	Affected / at Risk (%)	# Events
Total	20/20 (100%)
Blood and lymphatic system disorders
Anaemia	13/20 (65%)
Cardiac disorders
Palpitations	4/20 (20%)
Ear and labyrinth disorders
Vertigo positional	1/20 (5%)
Eye disorders
Conjunctivitis allergic	1/20 (5%)
Gastrointestinal disorders
Nausea	12/20 (60%)
Constipation	7/20 (35%)
Vomiting	7/20 (35%)
Stomatitis	3/20 (15%)
Abdominal pain lower	1/20 (5%)
Abdominal pain upper	1/20 (5%)
Diarrhoea	1/20 (5%)
Food poisoning	1/20 (5%)
Gastrooesophageal reflux disease	1/20 (5%)
Intestinal obstruction	1/20 (5%)
Retching	1/20 (5%)
Tongue discolouration	1/20 (5%)
General disorders
Malaise	6/20 (30%)
Fatigue	1/20 (5%)
Infections and infestations
Nasopharyngitis	3/20 (15%)
Sinusitis	1/20 (5%)
Upper respiratory tract infection	1/20 (5%)
Investigations
Platelet count decreased	10/20 (50%)
Neutrophil count decreased	6/20 (30%)
Blood creatinine increased	4/20 (20%)
White blood cell count decreased	4/20 (20%)
Gamma-glutamyltransferase increased	2/20 (10%)
Weight decreased	2/20 (10%)
Alanine aminotransferase increased	1/20 (5%)
Aspartate aminotransferase increased	1/20 (5%)
Blood alkaline phosphatase increased	1/20 (5%)
Eastern Cooperative Oncology Group performance status worsened	1/20 (5%)
Lymphocyte count decreased	1/20 (5%)
Metabolism and nutrition disorders
Decreased appetite	5/20 (25%)
Hyperkalaemia	1/20 (5%)
Hypoalbuminaemia	1/20 (5%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/20 (5%)
Myalgia	1/20 (5%)
Nervous system disorders
Headache	6/20 (30%)
Dysgeusia	3/20 (15%)
Dizziness	1/20 (5%)
Neuropathy peripheral	1/20 (5%)
Psychiatric disorders
Insomnia	1/20 (5%)
Renal and urinary disorders
Proteinuria	1/20 (5%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	3/20 (15%)
Dysphonia	1/20 (5%)
Dyspnoea	1/20 (5%)
Laryngeal discomfort	1/20 (5%)
Oropharyngeal pain	1/20 (5%)
Skin and subcutaneous tissue disorders
Alopecia	2/20 (10%)
Nail disorder	1/20 (5%)
Onychomadesis	1/20 (5%)
Photosensitivity reaction	1/20 (5%)
Pruritus	1/20 (5%)
Vascular disorders
Hypertension	3/20 (15%)
Orthostatic hypotension	1/20 (5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.