Phase 3
N=553
A Maintenance Study With Niraparib Versus Placebo in Patients With Platinum Sensitive Ovarian Cancer
Ovarian Neoplasms · Platinum Sensitive Ovarian Cancer
Bottom Line
View on ClinicalTrials.gov: NCT01847274 ↗Enrolled (actual)
553
Serious AEs
24.9%
Results posted
May 2019
Primary outcome: Primary: Progression-Free Survival (PFS) in Cohort With Germline BReast CAncer Gene (BRCA) Mutation (gBRCA) — 21; 5.5 months — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Active comparator: Niraparib (Drug); placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Female
- Sponsor
- Tesaro, Inc.
- Primary completion
- Apr 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression-Free Survival (PFS) in Cohort With Germline BReast CAncer Gene (BRCA) Mutation (gBRCA) |
21; 5.5 | <0.0001 sig |
| PRIMARY Progression-Free Survival (PFS) in Cohort With No Germline BCRA With Homologous Recombination Deficiency-positive (HRD+) Tumors (Non-gBRCAmut HRD+) |
12.9; 3.8 | <0.0001 sig |
| PRIMARY Progression-Free Survival (PFS) in Cohort With No Germline BRCA Mutation |
9.3; 3.9 | <0.0001 sig |
| SECONDARY Time to First Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA) |
19.1; 8.6 | 0.0005 sig |
| SECONDARY Time to First Subsequent Therapy in Cohort With No Germline BRCA Mutation |
12.4; 7.4 | <0.0001 sig |
| SECONDARY Chemotherapy-Free Interval in Cohort With Germline BRCA Mutation (gBRCA) |
20.0; 9.4 | <0.0001 sig |
| SECONDARY Chemotherapy-Free Interval in Cohort With No Germline BRCA Mutation |
13.4; 8.7 | <0.0001 sig |
| SECONDARY Progression-Free Survival 2 in Cohort With Germline BRCA Mutation (gBRCA) |
29.9; 22.7 | 0.0302 sig |
| SECONDARY Progression-Free Survival 2 in Cohort With No Germline BRCA Mutation |
19.5; 16.1 | 0.0748 |
| SECONDARY Overall Survival in Cohort With Germline BRCA Mutation (gBRCA) |
40.9; 38.1 | 0.3580 |
| SECONDARY Overall Survival in Cohort With No Germline BRCA Mutation |
31.0; 34.8 | 0.6868 |
| SECONDARY Time to Second Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA) |
29.7; 19.6 | 0.0061 sig |
| SECONDARY Time to Second Subsequent Therapy in Cohort With No Germline BRCA Mutation |
20.3; 16.7 | 0.1674 |
| SECONDARY Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 2 |
-0.8; -0.3 | — |
| SECONDARY Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 4 |
-0.1; -0.3 | — |
| SECONDARY Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 6 |
0.5; -0.5 | — |
| SECONDARY Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Post-progression |
-0.751; -1.324 | — |
| SECONDARY Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 2 |
-1.0; -0.3 | — |
| SECONDARY Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 4 |
-0.7; -0.9 | — |
| SECONDARY Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 6 |
-0.2; -0.9 | — |
| SECONDARY Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Post-progression |
-2.595; -1.801 | — |
| SECONDARY Change From Baseline in European Quality of Life Scale, 5-Dimensions (EQ-5D-5L) in Cohort With Germline BRCA at Cycle 2 |
-0.008; -0.008 | — |
| SECONDARY Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 4 |
-0.010; -0.035 | — |
| SECONDARY Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 6 |
0.002; -0.004 | — |
| SECONDARY Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Post-progression |
-0.041; -0.013 | — |
| SECONDARY Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 2 |
-0.007; -0.011 | — |
| SECONDARY Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 4 |
-0.004; -0.014 | — |
| SECONDARY Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 6 |
0.005; -0.011 | — |
| SECONDARY Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Post-progression |
-0.047; -0.050 | — |
| SECONDARY Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline |
47; 26; 32; 12; 24; 9 | 0.7969 |
| SECONDARY Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2 |
48; 25; 22; 5; 17; 15 | 0.2399 |
| SECONDARY Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4 |
47; 20; 22; 6; 20; 7 | 0.8566 |
| SECONDARY Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6 |
44; 17; 17; 5; 13; 7 | 0.8521 |
| SECONDARY Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression |
31; 15; 20; 9; 7; 3 | 0.9997 |
| SECONDARY Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline |
71; 40; 58; 26; 37; 16 | 0.9367 |
| SECONDARY Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2 |
69; 32; 39; 17; 30; 12 | 0.5037 |
| SECONDARY Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4 |
54; 31; 37; 16; 34; 17 | 0.9599 |
| SECONDARY Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6 |
43; 16; 29; 10; 30; 11 | 0.5921 |
| SECONDARY Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression |
57; 32; 45; 12; 23; 16 | 0.0259 sig |
| SECONDARY Number of Participants With Concordance of a Candidate Companion BRAC Analysis Diagnostic Test Compared to the Centralized BRCA Mutation Test Used in This Study |
— | — |
| SECONDARY Number of Participants With Concordance of a Candidate Companion HRD Diagnostic Test Compared to the HRD Test Used in This Study |
— | — |
| SECONDARY Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs) |
136; 62; 231; 110; 51; 9 | — |
| SECONDARY Number of Participants With Non-serious AEs and SAEs (Post-study Unblinding) |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Non-serious AEs and SAEs in FE Sub-study |
4; 6; 1; 0 | — |
| SECONDARY Number of Participants With Non-serious AEs and SAEs in QTc Sub-study |
24; 12 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-infinity]) Following Administration of Niraparib (FE Sub-study) |
29016.1; 31194 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUC[0-last]) Following Administration of Niraparib (FE Sub-study) |
28638.1; 27186.4 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) Following Administration of Niraparib (FE Sub-study) |
803.7; 582.1 | — |
| SECONDARY Time to Reach Maximum (Tmax) Following Administration of Niraparib (FE Sub-study) |
3.1; 6.1 | — |
| SECONDARY Terminal Elimination Half-life (t1/2) Following Administration of Niraparib (FE Sub-study) |
50.5; 47.9 | — |
| SECONDARY Number of Participants With Maximum Post-Baseline QT Interval Corrected by Fridericia's Formula (QTcF) Greater Than Pre-specified Thresholds |
2; 0; 0 | — |
Summary
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study of niraparib as maintenance in platinum sensitive ovarian cancer patients who have either gBRCAmut or a tumor with high-grade serous histology and who have responded to their most recent chemotherapy containing a platinum agent. Niraparib is an orally active PARP inhibitor. Niraparib or placebo (in a 2:1 ratio) will be administered once daily continuously during a 28-day cycle. Health-related quality of life will be measured by the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI), European Quality of Life scale, 5-Dimensions (EQ-5D), and a neuropathy questionnaire. Safety and tolerability will be assessed by clinical review of adverse events (AEs), physical examinations, electrocardiograms (ECGs), and safety laboratory values.
The primary objective of this study is to evaluate efficacy of niraparib as maintenance therapy in patients who have platinum sensitive ovarian cancer as assessed by the prolongation of progression free survival (PFS).
Eligibility Criteria
Inclusion Criteria
- 18 years of age or older, female, any race
- Histologically diagnosed ovarian cancer, fallopian tube cancer or primary peritoneal cancer
- High grade (or grade 3) serous histology or known to have gBRCAmut
- Has received at least 2 previous courses of platinum-containing therapy, and has disease that was considered platinum sensitive following the penultimate (next to last) platinum course (more than 6 month period between penultimate platinum regimen and progression of disease)
- Has responded to last the platinum regimen, remains in response and is enrolled on study within 8 weeks of completion of the last platinum regimen
- ECOG 0-1
- Adequate bone marrow, kidney and liver function
Exclusion Criteria
- Known hypersensitivity to the components of niraparib
- Invasive cancer other than ovarian cancer within 2 years (except basal or squamous cell carcinoma of the skin that has been definitely treated)
- Symptomatic uncontrolled brain metastasis
- Is pregnant or breast feeding
- Immunocompromised patients
- Known active hepatic disease
- Prior treatment with a known PARP inhibitor
Data sourced from ClinicalTrials.gov (NCT01847274). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.