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
- Parkland Health & Hospital System
David Miller, M.D.
This study is a multicenter, open-label, single-arm, Phase 2 study evaluating the safety and efficacy of niraparib in patients with advanced, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer with recurrent disease who were previously treated with chemotherapy and experienced a response lasting at least 6 months to first-line platinum-based therapy. Patients must have received 3 or 4 previous chemotherapy regimens (including, but not limited to, gemcitabine, doxorubicin, topotecan, carboplatin, oxaliplatin, cisplatin, bevacizumab, or PaRP inhibitors as single agents or in combination per standard of care). The study will assess whether treatment with niraparib will benefit this population in terms of the overall response rate (oRR). additionally, duration of response (DoR), DCR, PFS, and oRR in gBRCamut (either a positive deleterious gBRCa mutation or genetic variant or a suspected deleterious mutation) and HRD-positive subgroups will be assessed as secondary endpoints. oS will be assessed in all enrolled patients.
For eligible patients, a tumor sample will be sent to a centralized laboratory for gBRCamut and HRD testing. archival tissue is required in order to enroll in the study; for patients who do not have archival tissue, tissue from a fresh biopsy must be obtained prior to study treatment initiation. Blood samples also will be collected for all patients during screening for determination of gBRCamut status. it is not necessary to wait for gBRCamut and HRD testing results for enrollment into the study.
in order to evaluate tumor markers, an optional fresh biopsy may be done at screening and at the end of treatment (eoT) visit.
1. Patients must be female and at least 18 years of age
2. Patients must provide written informed consent
3. Patients must agree to undergo tumor HRD testing and blood gBRCAmut status testing
a. This test result must show that patients have an HRD-positive tumor, defined by the presence of a deleterious or suspected deleterious breast cancer gene (BRCA) mutation or be positive for genomic instability (Please see HRD results sample form
in Appendix F).
Note: The study HRD test result must be received prior to enrolment. The tumor sample may be submitted for HRD testing prior to the screening period if it appears the patient is likely to meet other eligibility requirements. To facilitate early testing, a separate informed consent form (ICF) specific for HRD testing will be required to be signed prior to testing.
b. If historic blood gBRCAmut is detected by a central gBRCAmut testing, then tumor HRD sample test results are not required prior to enrolment, however HRD testing still needs to be performed.
Note: If gBRCAmut status is known by a local test, then a fresh sample must be
submitted for centralized gBRCAmut testing. Local gBRCAmut results are not
acceptable for enrolment. Only patients with centralized gBRCAmut and/or HRDpositive
samples can be enrolled in this study.
4. 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.
5. Patients must have completed 3 or 4 previous chemotherapy regimens (eg, gemcitabine, doxorubicin, topotecan, carboplatin, oxaliplatin, cisplatin, bevacizumab, or PARP inhibitors as single agents or in combination per standard of care).
---Patients must have completed their last chemotherapy regimen > 4 weeks prior to treatment initiation.
6. Patients must have measurable disease according to RECIST (v.1.1)
7. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status
of 0 or 1 (see Appendix C)
8. Patients must have adequate organ function, defined as follows:
a. Absolute neutrophil count >=1500/[MICRO-SYMBOL]L
b. Platelets >=100,000/[MICRO-SYMBOL]L
c. Hemoglobin >=9 g/dL
d. Serum creatinine <=1.5 x upper limit of normal (ULN) or calculated creatinine
clearance >=60 mL/min using the Cockcroft-Gault equation
e. Total bilirubin <=1.5 x ULN OR direct bilirubin <=1 x ULN
f. Aspartate aminotransferase and alanine aminotransferase <=2.5 x ULN unless liver
metastases are present, in which case they must be <=5 x ULN
9. 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
10. Patients must be able to take oral medications
11. 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
12. Patients must be either postmenopausal, free from menses for >12 months, surgically
sterilized, or willing to use adequate contraception to prevent pregnancy or must agree to
abstain from heterosexual activity throughout the study, starting with enrollment through 90 days after the last dose of study treatment (see Appendix E for contraception
13. Patients must agree to blood samples during screening and at the end of treatment for cytogenetic analysis.