Maintenance Niraparib Plus Ipilimumab in Patients With Metastatic Pancreatic Adenocarcinoma Whose Disease Has Not Progressed on Platinum-Based Chemotherapy

NCT06747845 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: UPCC 19224
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 2

Brief Summary

The main goal of this study is to look at the effectiveness and anti-tumor activity (preventing growth of the tumor) of the drugs niraparib and ipilimumab, on the patients and their pancreatic cancer. This study will involve two different treatment arms. In Arm A, patients will receive niraparib plus ipilimumab. In Arm B, patients will receive standard chemotherapy. The main questions the study aims to answer are:

• Does niraparib plus ipilimumab slow down tumor growth in patients with pancreatic cancer?
• What medical problems do participants have when taking niraparib plus ipilimumab? Participants will:
• Undergo screening procedures to evaluate their cancer, overall health, and suitability for the study
• After passing screening, will be randomized to Arm A or B and be scheduled to receive niraparib plus ipilimumab (Arm A) or chemotherapy (Arm B)
• Receive niraparib plus ipilimumab every 3 weeks (Arm A)
• Receive chemotherapy every 2 weeks (Arm B)
• Visit the clinic for regular checkups and tests

Conditions

Pancreatic Adenocarcinoma Metastatic

Keywords

Niraparib; Ipilimumab; Pancreatic ductal adenocarcinoma; PDAC; Maintenance cancer therapy; Platinum-based therapy; PARP inhibitor; anti-CTLA-4 therapy

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) in the experimental arm

  PFS is defined as the time from randomization to the occurrence of disease progression according to RECIST v1.1, as assessed by the investigator, or death from any cause. Median PFS and 95% confidence interval will be estimated from the Kaplan-Meier curve. In the primary outcome measure, PFS will be assessed in Arm A.

  From Cycle 1 (each cycle in Arm A is 21 days) Day 1 to disease progression, loss to follow-up or death from any cause, whichever came first, assessed up to 42 months.

Secondary Outcomes (7)

• Overall response rate (ORR) in the experimental arm

  From first restaging assessment through completion of study treatment (maximum 42 months)

• Overall survival (OS) in the experimental arm

  From Cycle 1 (each cycle in Arm A is 21 days) Day 1 until death, loss to follow-up, withdrawal of consent or until 5 years have passed, whichever occurs first

• Disease Control in the experimental arm

  From Cycle 1 (each cycle in Arm A is 21 days) Day 1 to disease progression, loss to follow-up or death from any cause, whichever came first, assessed up to 42 months..

• Safety and tolerability of Niraparib plus Ipilimumab in the experimental arm

  From Cycle 1 (each cycle in Arm A is 21 days) Day 1 through 90 days after patient End of Treatment Visit

• PFS in the control arm

  From Cycle 1 (each cycle in Arm B is 28 days) Day 1 to disease progression, loss to follow-up or death from any cause, whichever came first, assessed up to 42 months.

Study Arms (2)

Niraparib + Ipilimumab (Arm A)

EXPERIMENTAL

niraparib + ipilimumab

Drug: Niraparib; Drug: Ipilimumab

FOLFIRI (Arm B)

OTHER

standard chemotherapy FOLFIRI

Drug: FOLFIRI

Interventions

Niraparib DRUG

Niraparib 200mg PO daily on days 1-21 of each 21-day cycle.

Also known as: Arm A

Niraparib + Ipilimumab (Arm A)

FOLFIRI DRUG

Standard chemotherapy FOLFIRI (5-fluorouracil, folinic acid, and irinotecan) will be administered intravenously every 14 days of a 28-day cycle.

Also known as: Arm B

FOLFIRI (Arm B)

Ipilimumab DRUG

Ipilimumab 3mg/kg IV day 1 of each cycle, for the first 4 cycles only.

Also known as: Arm A

Niraparib + Ipilimumab (Arm A)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma with metastatic disease
• ≥18 years of age
• Patients must be able to understand the study procedures and agree to participate in the study by providing written informed consent
• Participants must have received 8-12 cycles (4-6 months) of first-line FOLFIRINOX or modified FOLFIRINOX for metastatic disease with stable disease or better. Patients treated with liposomal irinotecan with oxaliplatin, 5-fluorouracil and leucovorin (NALIRIFOX) are also eligible. Patients who were initially treated with FOLFIRINOX or NALIRIFOX but stopped oxaliplatin because of toxicity are eligible for the trial.
• Note: This requires at least stable imaging and a stable or decreasing tumor marker as applicable and as determined by the investigator.
• Measurable disease is not a requirement for study entry.
• Note: The study will require that at least 80% of enrolled patients (ie 55 of all patients) are biopsiable at enrollment. The investigators may require measurable/biopsiable disease as the study progresses in order to achieve this goal.
• Participants must be willing to undergo a pre-treatment fresh tumor biopsy (if medically feasible).
• Participants must be willing to undergo an on-treatment tumor biopsy (if medically feasible).
• Female participant has a negative serum pregnancy test within 24 hours prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 6 months (females) or 30 days (males) after the last dose of study treatment, or is of nonchildbearing potential.
• Male patient agrees to use an adequate method of contraception starting with the first dose through 90 days after the last dose of study treatment.
• Adequate organ function confirmed by the following laboratory values obtained ≤7 days prior to the first day of study therapy:
• Absolute neutrophil count (ANC) ≥1.5 x 109/L
• Platelets\>100 x 109/L
• Hemoglobin ≥9g/dL

You may not qualify if:

• Prior treatment with a PARP inhibitor, ipilimumab, or other cytotoxic T-lymphocyte-associated-4 protein (CTLA-4) inhibitor.
• Patients who have demonstrated resistance to FOLFIRINOX are not eligible to participate in this study
• Patients with known pathogenic/likely pathogenic germline or somatic alteration(s) in BRCA1, BRCA2, PALB2, RAD51C, or RAD51D.
• Patients with known mismatch repair deficiency or microsatellite instability-high cancer.
• Clinical evidence of uncontrolled malabsorption and/or any other gastrointestinal disorder or defect that would, in the opinion of the investigator, interfere with the absorption of niraparib
• Patients with uncontrolled hypertension, defined as systolic BP \>140mmHg and/or diastolic BP \>90mmHg
• Patients with a prior history of posterior reversible encephalopathy syndrome (PRES)
• Acute infection requiring intravenous antibiotics, intravenous antiviral or intravenous antifungal agents during the 14 days prior to first dose of study therapy
• Patients will be excluded if they have a history of or active autoimmune disease, defined as: patients with a history of inflammatory bowel disease are excluded from this study, as are patients with a history of symptomatic autoimmune disease (e.g. rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus, autoimmune vasculitis e.g. Wegener's Granulomatosis); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome).
• Note: Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
• Has a history of interstitial lung disease or active, non-infectious pneumonitis
• Has received a live vaccine within 4 weeks prior to the first dose of trial therapy
• Note: seasonal influenza vaccines for injection are generally inactivated and are allowed; however intranasal influenza vaccines (e.g. Flu-Mist®) are live attenuated vaccines and are not allowed.
• For fertile patient (female able to become pregnant or male able to father a child), refusal to use effective contraception during the period of the trial and:
• Female patients refusing to use effective contraception for 6 months after the last dose of study drug.

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead
• Lustgarten Foundation: collaborator
• GlaxoSmithKline: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (2)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

NOT YET RECRUITING

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Interventions

niraparib; IFL protocol; Ipilimumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Kim Reiss Binder, MD

CONTACT

215-360-0735; kim.reissbinder@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2024
• First Posted: December 24, 2024
• Study Start: May 7, 2025
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): January 30, 2029
• Last Updated: September 16, 2025

Record last verified: 2025-09

Locations

US (2)