PRIMA Study Objectives
The primary objective of this study is to evaluate the efficacy of niraparib versus placebo as maintenance treatment in patients with Stage III or IV ovarian cancer (including fallopian and peritoneal cancers) with a homologous recombination deficiency (HRD)-positive tumor and a CR or PR following front-line platinum-based chemotherapy treatment as assessed by the prolongation of PFS.
- To evaluate additional measures of clinical benefit for niraparib versus placebo as maintenance treatment, such as OS, PROs, and time to progression on the next anticancer therapy (PFS2)
- To evaluate the safety and tolerability of niraparib versus placebo
Key Inclusion Criteria
- Patients must be female ≥18 years of age
- Patients must have histologically diagnosed ovarian cancer, fallopian tube cancer, or primary peritoneal cancer that is Stage III or IV according to FIGO criteria
- Stage III patients who have undergone debulking surgery must have had residual disease after debulking surgery unless the patient has undergone neoadjuvant therapy
- Patients must meet the following front-line therapy requirements:
- Patients must have had at least 4 cycles of front-line platinum-based (eg, carboplatin, oxaliplatin, or cisplatin) therapy
- Patients must have achieved a complete or partial (no measurable lesion >2 cm) tumor response to platinum-based regimen per RECIST criteria
- Patients must have either CA-125 in the normal range or CA-125 decrease by more than 90% during their front-line therapy
- Patients must agree to undergo HRD testing
- This test result must show that patients have an HRD-positive tumor
- Patients of childbearing potential must have a negative serum pregnancy test (beta hCG) within 72 hours prior to receiving the first dose of study treatment
Key Exclusion Criteria
- Patients must not be pregnant, breastfeeding, or expecting to conceive children while receiving study treatment and for 3 months after the last dose of study treatment
- Patients must not have a known hypersensitivity to the components of niraparib or the excipients
- Patients must not be simultaneously enrolled in any clinical trial of niraparib or any other investigational therapy
- Patients must not have received prior treatment with a known PARP inhibitor or have participated in a study where any treatment arm included administration of a known PARP inhibitor
- Patients must not have had investigational therapy administered within 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior to the first scheduled day of dosing in this study
- Patients must not have had any known, persistent (>4 weeks), ≥Grade 3 hematological toxicity or fatigue from prior cancer therapy
- Patients must not have any known history of MDS or a pre-treatment cytogenetic testing result at risk for a diagnosis of MDS/acute myeloid leukemia (AML)
QUADRA Study Objectives
The primary objective of this study is to evaluate the safety and efficacy of niraparib in ovarian cancer patients who have received 3 or 4 previous chemotherapy regimens. The primary outcome measure is antitumor activity.
Secondary outcome measures:
- Durability of anti-cancer activity (i.e. time from first response, CR or PR until disease progression).
The evaluation is measured by clinical review of adverse events (AEs), physical examinations, electrocardiograms (ECGs), RECIST tumor assessments and safety laboratory values.
- Antitumor activity of niraparib in HRD+ and gBRCAmut
- Disease Control Rate
- Progression Free Survival
Time from enrollment to the earlier date of assessment of progression by any cause in the absence of progression per RECIST (v.1.1) or clinical criteria, or death.
- Safety and tolerability of niraparib in ovarian cancer patients (Review of adverse events, concomitant medications, physical exams, electrocardiograms (ECGs), and safety lab values).
- Patients of childbearing potential must have negative pregnancy serum test within 72 hours of being dosed
- Histologically diagnosed recurrent high-grade serous epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer
- Must have completed at least 3 previous chemotherapy regimens (e.g. PARP inhibitors as single agents or in combination per standard of care)
- ECOG 0-1
- Adequate bone marrow, kidney and liver function
- Known hypersensitivity to the components of niraparib
- Symptomatic uncontrolled brain metastasis
- Invasive cancer other than ovarian cancer within 2 years (except basal or squamous cell carcinoma of the skin that has been definitely treated)
- Is pregnant or breast feeding
- Immunocompromised patients
- Known active hepatic disease