Phase 2
Completed N=105
A Study of Niraparib Combined With Bevacizumab Maintenance Treatment in Participants With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy
Source: ClinicalTrials.gov NCT03326193 ↗Enrolled (actual)
105
Serious AEs
30.5%
Results posted
Jan 2022
Primary outcomePrimary: Progression Free Survival (PFS) Rate — 62 Percentage of participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression Free Survival (PFS) Rate |
62 | — |
| SECONDARY Progression Free Survival (PFS) by RECIST v 1.1 |
19.6 | — |
| SECONDARY Overall Survival (OS) |
61.1 | — |
| SECONDARY RECIST or Cancer Antigen (CA)-125 Progression Free Survival |
16.9 | — |
| SECONDARY Change From Baseline (CFB) in Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) |
25.7; -1.4; -1.7; -0.3; -1.1; -1.1 | — |
| SECONDARY Time to First Subsequent Therapy (TFST) |
17.5 | — |
| SECONDARY Time to Second Subsequent Therapy (TSST) |
38.6 | — |
| SECONDARY Percentage of Participants With Treatment-emergent Adverse Events (TEAEs), Non-serious TEAEs and Treatment-emergent Serious Adverse Events (TESAEs) |
100; 100; 30.5 | — |
| SECONDARY Number of Participants With TEAEs Leading to Niraparib Treatment Discontinuation |
46 | — |
| SECONDARY Number of Participants With TEAEs Leading to Niraparib Dose Reductions |
81 | — |
| SECONDARY Number of Participants With AEs of Special Interest (AESI) |
4; 2 | — |
| SECONDARY Change From Baseline (CFB) in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) |
129.7; 2.8; 78.2; 0.3 | — |
| SECONDARY Change From Baseline (CFB) in Pulse Rate |
80.6; 4.3 | — |
| SECONDARY Change From Baseline (CFB) in Temperature |
36.59; -0.01 | — |
| SECONDARY Number of Participants Who Used Concomitant Medications |
100 | — |
| SECONDARY Change From Baseline (CFB) in Hematology Parameters: Basophils, Eosinophil, Leukocytes, Platelets, Lymphocytes, Monocytes and Neutrophils |
0.025; 0.008; 0.168; -0.028; 5.523; 0.660 | — |
| SECONDARY Change From Baseline (CFB) in Hematology Parameter: Hemoglobin (Hb) |
116.800; 4.787 | — |
| SECONDARY Change From Baseline (CFB) in Hematology Parameter: Erythrocyte Mean Corpuscular Volume (MCV) |
97.560; 0.093 | — |
| SECONDARY Change From Baseline (CFB) in Clinical Chemistry Parameters: Urea Nitrogen, Glucose, Calcium, Chloride, Sodium, Magnesium and Potassium |
5.681; 0.375; 5.996; -0.073; 2.377; 0.018 | — |
| SECONDARY Change From Baseline (CFB) in Clinical Chemistry Parameters: Bilirubin and Creatinine |
6.242; 1.168; 65.577; 9.339 | — |
| SECONDARY Change From Baseline (CFB) in Clinical Chemistry Parameters: Albumin and Protein |
41.629; 0.926; 70.619; 0.309 | — |
| SECONDARY Change From Baseline (CFB) in Clinical Chemistry Parameters: Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) |
24.619; 5.117; 23.590; 4.362 | — |
Eligibility Criteria
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 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.
- 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.
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 = 1.0 at screening or urine dipstick for proteinuria ≥ 2 (participants discovered to have >=2 proteinuria on dipstick at baseline should undergo
Data sourced from ClinicalTrials.gov (NCT03326193). 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. Informational only — not medical advice.