Niraparib As First Line Therapy With Metastatic Homologous Repair-deficient Pancreatic Cancer

Study Overview

Niraparib As First Line Therapy with Metastatic Homologous Repair-deficient Pancreatic Cancer

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.

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.

Metastatic Pancreatic Cancer

DRUG: Niraparib

ET21-169

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2022-06-23	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2024-09-06
First Submitted that Met QC Criteria 2022-06-30	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2024-09-19
First Posted (ACTUAL) 2022-07-05	Results First Posted N/A	Last Verified 2024-09

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Niraparib	DRUG: Niraparib 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. 300 mg/day, continuously for patients

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Niraparib

DRUG: Niraparib

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. 300 mg/day, continuously for patients

Primary Outcome Measures	Measure Description	Time Frame
Efficacy of niraparib in patients with HR-deficient pancreatic cancer	Objective response rate at Week 16 (ORR-16W) according to RECIST V1.1	16 weeks

Secondary Outcome Measures	Measure Description	Time Frame
Disease control rate (DCR)	After 16 weeks of treatment (DRC-16W) according to RECIST V1.1	16 weeks
Best overall response Rate	According to RECIST V1.1	At least 12 months following inclusion
Duration of response (DoR)		At least 12 months following inclusion
Progression Free survival (PFS)		At least 12 months following inclusion
Overall survival (OS)		At least 12 months following inclusion
Safety and tolerability of niraparib in pancreatic cancer patients	incidence and severity of AEs (with severity determined according to NCI CTCAE v5.0)	At least 12 months following inclusion

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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 ≥ 5mm2.
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:

Absolute neutrophil count ≥ 1.5 109/L
Platelets ≥ 100 109/L
Hemoglobin ≥ 9 g/dL (without transfusion within 7 d)
Serum creatinine OR Creatinine clearance according to CKD-EPI ≥ 30 mL/min/1.73 m2 for patient with creatinine levels > 1.5 ULN

Resting blood pressure systolic < 140 mmHg and diastolic <90 mmHg.
Women patients of child-bearing potential are eligible, provided they have a negative serum or urine pregnancy test within 3 days prior to C1D1, and agrees to use a highly effective contraception (See section appendix) beginning signing the ICF to 6 months after the final dose of study drug.
Fertile men must agree to use an effective method of contraception (See section appendix) during the study and for up to 3 months after the last dose of study drug and to not donate sperm during the same period.
Patient should understand, sign, and date the written voluntary informed consent form prior to any protocol-specific procedures performed and should be able and willing to comply with study visits and procedures as per protocol.
Patients must be covered by a medical insurance.

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
Prior organ or bone marrow transplant.
Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results.
Pregnant or lactating women.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

GlaxoSmithKline

Investigators

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

Learn

Resources

PatientS

Caregivers

Clinical Trial Record