A Study of Niraparib in Patients With Ovarian Cancer Who Have Received Three or Four Previous Chemotherapy Regimens

Study Overview
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Brief Summary
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This is a Phase 2, open-label, single arm study to evaluate the safety and efficacy of niraparib in ovarian cancer patients who have received three or four previous chemotherapy regimens. Niraparib is an orally active PARP inhibitor. Niraparib will be administered once daily continuously during a 28-day cycle. Health-related quality of life will be measured by Eastern Cooperative Oncology Group performance status (ECOG). Safety and tolerability will be assessed by clinical review of adverse events (AEs), physical examinations, electrocardiograms (ECGs), RECIST tumor assessments and safety laboratory values.

Official Title
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A Phase 2, Open-Label, Single-Arm Study to Evaluate the Safety and Efficacy of Niraparib in Patients With Advanced, Relapsed, High-Grade Serous Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Have Received Three or Four Previous Chemotherapy Regimens

Conditions
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Ovarian Cancer, Ovarian Neoplasms

Intervention / Treatment
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* Drug: Niraparib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must agree to undergo tumor HRD testing and blood gBRCAmut status testing. Patients of childbearing potential must have negative pregnancy serum test within 72 hours of being dosed Patients must have histologically diagnosed 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 experienced a response lasting at least 6 months to first-line platinum based therapy. Patients Must have completed 3 or 4 previous chemotherapy regimens. Patients must have completed their last chemotherapy regimen > 4 weeks prior to treatment initiation. Patients must have measurable disease according to RECIST (v.1.1). Patients 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. Patients must agree to blood samples during screening and at the end of treatment for cytogenetic analysis. Exclusion Criteria: Patients must not have any known, persistent (> 4 weeks), ≥Grade 3 hematologic toxicity during the last cancer therapy. Patients must not have any known, persistent (>4 weeks), ≥ Grade 3 fatigue during the last cancer therapy. Patients must not have received pelvic radiotherapy as treatment for primary or recurrent disease within 1 year of the first dose of study treatment. Patients must not have symptomatic uncontrolled brain or leptomeningeal metastases. Patients must not be considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active, uncontrolled infection. Patients must not have received a transfusion (platelets or red blood cells) within 4 weeks of the first dose of study treatment. Patients must not have known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Niraparib<br> | Drug: Niraparib<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | The 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) (version1.1), where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 millimeters (mm) in the short axis, PR=At least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. Primary Analysis Population comprised of participants who received 3 or 4 prior lines of therapy (LOT), had homologous recombination deficiency positive (HRDpos) tumors, had platinum-sensitive disease, and were poly(adenosine 5'-diphosphate [ADP]-ribose) polymerase inhibitors (PARPi) naïve. | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DoR) | DoR was defined as the time from first documentation of CR or PR until the time of first documentation of disease progression (PD) as assessed by the Investigator per RECIST (version1.1). DoR was analyzed using Kaplan-Meier (KM) method. | Up to 3 years | 
| ORR by HRD Status and Breast Cancer Gene (BRCA) Status | The ORR was defined as the percentage of participants achieving CR or PR as assessed by the Investigator per RECIST (version1.1), where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. ORR was evaluated for participants with following characteristics: HRD status (positive, negative and unknown) and BRCA status (mutation positive, wild-type and unknown). | Up to 3 years | 
| Disease Control Rate (DCR) | Disease control rate was defined as the percentage of participants achieving CR, PR, or stable disease (SD) as assessed by the Investigator per RECIST (version1.1). The exact (Clopper-Pearson) method was used to calculate 95% confidence interval. | Up to 3 years | 
| Progression Free Survival | Progression-free survival was defined as the time from the date of first dose to the earlier date of assessment of progression or death by any cause in the absence of progression as assessed by the Investigator per RECIST (version 1.1) or clinical criteria. Progression is defined using RECIST version1.1 as at least a 20% increase in the sum of the diameter of target lesions or unequivocal progression of existing non-target lesions or the appearance of one or more new lesions. | Up to 3 years | 
| Overall Survival | Overall Survival was defined as the time from the date of the first dose to the date of death by any cause. It was calculated as (Date of Death minus First dose date plus 1) divided by 30.4375. | Up to 3 years | 
| Time to First Subsequent Therapy (TFST) | Time to first subsequent therapy (TFST) was defined as the time from the date of first dose to the date of first subsequent therapy or death, whichever occurs first. It was calculated as (Earlier of [First dose of first subsequent therapy or death] minus First dose date plus 1) divided by 30.4375. | Up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gBRCAmut, BRCA, PARP inhibitor, HRD, Ovarian cancer, Serous Epithelial, Fallopian Tube, Primary Peritoneal