A Multicentric, Single Arm, Phase II Trial Assessing the Efficacy of Niraparib as First Line Therapy for Patients With Metastatic Homologous Repair-deficient Pancreatic Cancer

Centre Leon Berard4 sites in 1 country2 target enrollmentOctober 28, 2022

ConditionsMetastatic Pancreatic Cancer

InterventionsNiraparib

DrugsNiraparib

Overview

Phase: Phase 2
Intervention: Niraparib
Conditions: Metastatic Pancreatic Cancer
Sponsor: Centre Leon Berard
Enrollment: 2
Locations: 4
Primary Endpoint: Efficacy of niraparib in patients with HR-deficient pancreatic cancer
Status: Terminated
Last Updated: 2 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This trial is a single arm open-label, phase II aiming to assess the clinical activity of niraparib in chemotherapy-naïve biomarker-selected pancreatic cancer patients.

Detailed Description

This trial is a single arm open-label, phase II aiming to assess the clinical activity (objective response rate at week16 according to RECIST V1.1) of niraparib in chemotherapy-naïve biomarker-selected pancreatic cancer patients. HR alterations must be confirmed before study drug start: only patients with mutation and/or rearrangement leading to inactivation in at least one of the following genes BARD1, BRCA1, BRCA2, BRIP1, FANCA, FANCD2, FANCL, MRE11, NBN, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, RAD54L are eligible. Eligible patients will receive niraparib once daily, per os, continuously until loss of clinical benefit, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurs first.

Registry

clinicaltrials.gov

Start Date

October 28, 2022

End Date

August 30, 2024

Last Updated

2 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Centre Leon Berard

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male or female patient ≥18 years of age at time of informed consent form signature.
•Histologically proven advanced/metastatic PDAC not curable by surgery and/or definitive radiotherapy and not previously exposed to chemotherapy in advanced/metastatic setting. See Note in the full protocol
•Documented deleterious alteration resulting in inactivation in at least one of the following genes BARD1, BRCA1, BRCA2, BRIP1, FANCA, FANCD2, FANCL, MRE11, NBN, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, RAD54L. See Notes in the full protocol
•Measurable disease at baseline according to RECIST V1.1 (See Section Appendix) See note in the full protocol
•Avaibility of a representative formalin-fixed paraffin-embedded (FFPE) sample of the primary or metastatic tumor tissue (resection or biopsy) with an associated pathology with the following quality/quantity control criteria: ≥30 % of tumor cells and a tumor surface area ≥ 5mm
•Optional - Tumor lesion visible by medical imaging and accessible to repeatable percutaneous or endoscopic sampling that permits core needle biopsy without unacceptable risk of a significant procedural complications, and suitable for retrieval of a minimum of 4 cores with a needle minimum diameter :16-gauge. See note in the full protocol.
•Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 (See Section Appendix)
•Life expectancy \> 16 weeks.
•Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 7 days prior to C1D1:
•Parameters Laboratory Value

Exclusion Criteria

•Patients not respecting the requirement for prior and concomitant treatment
•Inability to swallow capsules (bowel obstruction) or hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
•Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases. See notes in the full protocol
•Patients with other malignancy unless this malignancy is not expected to interfere with the evaluation of study endpoints (eg, basal or squamous cell carcinoma of the skin, in-situ carcinoma of the cervix, localized prostate cancer), or with no evidence of disease for ≥ 2 years.
•Any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
•History of severe allergic or other hypersensitivity reactions to any component of niraparib.
•Patients with:
•Active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) unless their HBV is stably controlled on nucleoside analogs (eg entecavir or tenofovir) which will be continued for the duration of the study. See note in the full protocol.
•Active hepatitis C. Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA, or
•HIV infection

Arms & Interventions

Niraparib

Intervention: Niraparib

Outcomes

Primary Outcomes

Efficacy of niraparib in patients with HR-deficient pancreatic cancer

Time Frame: 16 weeks

Objective response rate at Week 16 (ORR-16W) according to RECIST V1.1

Secondary Outcomes

Duration of response (DoR)(At least 12 months following inclusion)
Disease control rate (DCR)(16 weeks)
Overall survival (OS)(At least 12 months following inclusion)
Best overall response Rate(At least 12 months following inclusion)
Progression Free survival (PFS)(At least 12 months following inclusion)
Safety and tolerability of niraparib in pancreatic cancer patients(At least 12 months following inclusion)