A Phase 3 Randomized Double-Blind Trial of Maintenance with Niraparib Versus Placebo in Patients with Platinum Sensitive Ovarian Cancer

Summary

This main study is a double-blind, 2:1 randomized, placebo controlled study in platinum sensitive ovarian cancer patients who have either gBRCamut or a tumor with high-grade serous histology. The patients must have received at least two platinum-based regimens, had a response to their last regimen, and have no measurable disease [Greater Than]2cm, and normal Ca125 (or [Greater Than]90% decrease) following their last treatment. The study will assess whether maintenance with niraparib will extend PFS in this population. There will be 2 independent patient cohorts, one with deleterious gBRCamut and the other with high-grade serous histology but without such gBRCa mutations based on the hypothesis that patients with gBRCa mutations will be enriched for responsiveness to niraparib.

BRCa mutation analysis will be sent for centralized testing at a reference laboratory. Cohort assignment will be determined prior to randomization, based on reference laboratory results.

a separate randomization list will be created for each cohort. Stratification factors will include time to progression after the penultimate (next to last) platinum therapy before study enrollment (6 to [Less Than]12 months and [GreaterThanorequalTo]12 months), use of bevacizumab in conjunction with the penultimate or last platinum regimen (yes/no), and best response during the last platinum regimen (complete response [CR] and partial response [PR]). an analysis of outcome by (1) concomitant chemotherapy with the platinum in the last and penultimate regimens (yes/no); (2) and number of prior platinum courses (2 and [Greater Than]2) will also be performed.

Clinic visits will occur in each cycle (every 4 weeks (+-)3 days). Response evaluation criteria in solid tumors (ReCiST) tumor assessment via computed tomography (CT) or magnetic resonance imaging (MRi) scan of abdomen/pelvis and clinically indicated areas is required at the end of every 2 cycles (8 weeks with a window of (+-)7 days from date of visit) through Cycle 14, then at the end of every 3 cycles (12 weeks with a window of (+-)7 days from date of visit) until progression. if a patient discontinues treatment for a reason other than progression, death, withdrawal of consent or lost to follow-up, scans should continue at the specified intervals. PRos (Functional assessment of Cancer Therapy x ovarian Symptom index [FoSi], european Quality of Life scale, 5-Dimensions [eQ-5D-5L], and a neuropathy questionnaire) will be collected in a coordinated fashion with ReCiST tumor imaging while on study treatment and following discontinuation of treatment, regardless of progression status (at the nearest study visit to the imaging exam, after every 2 cycles through Cycle 14, then after every 3 cycles). if the patient discontinues study treatment, assessment of PRos will be performed at that time and then 8 weeks ((+-)2 weeks) later, regardless of subsequent treatment. The PRos may be completed remotely. it is estimated that PRo evaluations will take less than 20 minutes at each time point. Since these are questionnaires, their completion will not interfere with, or preclude, future treatment or clinical studies. after treatment discontinuation, study information on patient reported outcomes, response, tolerability with subsequent anti-cancer treatment, and survival will continue to be collected.

Patients will continue to receive their assigned treatment until disease progression (determined using ReCiST v.1.1 criteria and clinical criteria), unacceptable toxicity, death, withdrawal of consent, or lost to follow-up, whichever comes first.



Participant Eligibility

1. Female, age at least 18 years
2. Patient agrees to undergo analysis of their germline BRCA status. (Testing must
be completed prior to randomization with sample submitted up to 3 months prior to randomization if it appears patient is likely to meet other eligibility requirements.)
3. Histologically diagnosed ovarian cancer, fallopian tube cancer or primary
peritoneal cancer
4. High grade (or grade 3) serous histology or known to have gBRCAmut
5. Patients must have completed at least 2 previous courses of platinum-containing
therapy (e.g. carboplatin, oxaliplatin or cisplatin):
a. For the penultimate (next to last) platinum based chemotherapy course
prior to enrollment on the study:
i. A patient must have platinum sensitive disease after this treatment; defined as achieving a response (CR or PR) and disease
progression greater than 6 months after completion of their last
dose of platinum therapy(document 6-12m or >12m); (Source
documentation required and may include physician or clinic
notes.)
b. For the last chemotherapy course prior to enrollment on the study:
i. Patients must have received a platinum-containing regimen for a
minimum of 4 cycles
ii. Patients must have achieved a partial or complete tumor response.
iii. Following the last regimen, patients must have either
1. CA125 in the normal range OR
2. CA125 decrease by more than 90% during their last
platinum regimen which is stable for at least 7 days (i.e.,
no increase >15%)
iv. Following the last regimen, patients must have no measurable
lesion >2cm at the time of study entry
Patients must be started on study treatment between 3 and 8 weeks after
completion of their final dose of the platinum-containing regimen.
Note: The last platinum regimen does not necessarily have to immediately follow the
next to last (penultimate) platinum regimen. For example, if a patient received a nonplatinum
regimen between the penultimate platinum regimen and last platinum regimen,
they could be eligible, so long as they meet all entry criteria.
6. The patient agrees to complete PROs during study treatment AND one additional
time point 8 weeks following study treatment discontinuation. It is estimated that
completion of PROs will take less than 20 minutes at each time point. Since these
are questionnaires, their completion will not interfere with, or preclude, future
treatment or clinical studies.
7. Formalin fixed, paraffin embedded archival tumor available from the primary or
recurrent cancer required for all non-gBRCAmut patients (and strongly encouraged
for gBRCAmut patients).
8. ECOG performance status 0-1.
9. Adequate organ function
a. Absolute neutrophil count (ANC) >=1,500/mcL
b. Platelets >=100,000/mcL
c. Hemoglobin >=9g/dL
d. Serum creatinine <=1.5x upper limit of normal (ULN) or calculated
creatinine clearance >=60mL/min using Cockcroft-Gault equation
e. Total bilirubin <=1.5x ULN OR direct bilirubin <= 1x ULN
f. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
<=2.5x ULN unless liver metastases are present, in which case they must be
<=5x ULN
10. Able to take oral medications
11. Women of childbearing potential must use adequate birth control for the duration of
study participation (Section 4.3).

Additional Inclusion Criteria for Food Effect Sub Study
With the exception of inclusion criteria 2, 4, 5, 6, 7 and 8 (above), all main study
inclusion criteria apply. In addition, the following inclusion criteria apply to the food
effect sub-study only:
1. Entry criteria are broadened to include patients with ovarian cancer regardless of
platinum sensitivity and burden of disease as long as no standard therapy exists or
the patient has refused standard therapy.
2. ECOG 0-2.
3. Must be able to eat a high-fat meal and fast for 12 hours.