Trials / Active Not Recruiting

Active Not RecruitingNCT03337087

Liposomal Irinotecan, Fluorouracil, Leucovorin Calcium, and Rucaparib in Treating Patients With Metastatic Pancreatic, Colorectal, Gastroesophageal, or Biliary Cancer

Phase I Study of Irinotecan Liposome (Nal-IRI), Fluorouracil and Rucaparib in the Treatment of Select Gastrointestinal Metastatic Malignancies Followed by a Phase Ib of First and Second Line Treatment of Both Unselected and Selected (for BRCA 1/2 and PALB2 Mutations) Patients With Metastatic Adenocarcinoma of the Pancreas Then Followed by a Phase II Study of First Line Treatment of Selected Patients With Metastatic Adenocarcinoma of the Pancreas With Genomic Markers (Signature) of Homologous Recombination Deficiency (HRD)

Status: Active Not Recruiting
Phase: Phase 1 / Phase 2
Study type: Interventional
Enrollment: 18 (actual)

Sponsor: Academic and Community Cancer Research United · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase I/II trial studies the side effects and best dose of liposomal irinotecan and rucaparib when given together with fluorouracil and leucovorin calcium and to see how well they work in treating patients with pancreatic, colorectal, gastroesophageal, or biliary cancer that has spread to other places in the body (metastatic). Chemotherapy drugs, such as liposomal irinotecan, fluorouracil, and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as rucaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Giving liposomal irinotecan and rucaparib together with fluorouracil and leucovorin calcium may work better in treating patients with pancreatic, colorectal, gastroesophageal, or biliary cancer.

Detailed description

PRIMARY OBJECTIVES: I. To establish the recommended dose level for the phase Ib and phase II trial of liposomal irinotecan (nal-IRI) and fluorouracil (5-FU) with rucaparib (MFR) in patients with metastatic disease from pancreatic cancer (up to 2 lines of prior therapy), colorectal cancer (up to 3 lines of prior therapy), gastroesophageal cancer (up to 1 line of prior therapy) and biliary tract cancer (with 1 line of prior therapy allowed). (Phase I) II. To assess, in a preliminary fashion, antitumor efficacy, in terms of disease control rate and further tolerability, of the recommended dose level of combination of nal-IRI and 5-FU with rucaparib in patients with metastatic disease from pancreatic cancer (=\< 1 line of prior therapy in the metastatic setting). (Phase Ib) III. To estimate the proportion of evaluable patients who reach complete response (CR)/partial response (PR) =\< 32 weeks after registration among patients with metastatic adenocarcinoma of the pancreas with genomic markers (signature) of homologous recombination deficiency (HRD), specifically BRCA1, BRCA2, and PALB2 mutation, treated with the combination of nal-IRI and 5FU with rucaparib (MFR). (Phase II) SECONDARY OBJECTIVES: I. To estimate the progression-free survival (PFS) and overall survival (OS) for patients with metastatic adenocarcinoma of the pancreas with genomic markers (signature) of homologous recombination deficiency (HRD), specifically BRCA1, BRCA2, and PALB2 mutation, treated with the combination of nal-IRI and 5-FU with rucaparib (MFR). (Phase II) II. To assess the toxicity of the combination of nal-IRI and 5-FU with rucaparib in patients with metastatic adenocarcinoma of the pancreas with genomic markers (signature) of homologous recombination deficiency (HRD), specifically BRCA1/2 and PALB2 mutations. (Phase II) EXPLORATORY OBJECTIVES: I. To evaluate the role of genomic markers (signature) of HRD, mutation other than BRCA1, BRCA2, and PALB2 as predictive biomarkers of response to MFR. II. To evaluate BRCA1, BRCA2, and PALB2 mutations as predictive biomarker of response to MFR. OUTLINE: This is phase I, dose-escalation study of liposomal irinotecan and rucaparib and followed by a phase II study. PHASE Ia: Patients receive liposomal irinotecan intravenously (IV) over 90 minutes, leucovorin calcium IV, and fluorouracil IV over 46 hours on days 1 and 15. Patients also receive rucaparib orally (PO) twice daily (BID) on days 4-13 and 18-27. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity. PHASE Ib/II: Patients receive liposomal irinotecan IV over 90 minutes and fluorouracil IV over 46 hours on days 1 and 15. Patients also receive rucaparib PO BID on days 4-13 and 18-27. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity. After completion of study treatment, patients are followed up every 6 months for 3 years.

Conditions

Interventions

Type	Name	Description
DRUG	Fluorouracil	Given IV
DRUG	Irinotecan Sucrosofate	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Leucovorin Calcium	Given IV
DRUG	Rucaparib	Given PO

Timeline

Start date: 2018-11-02
Primary completion: 2021-03-31
Completion: 2025-08-09
First posted: 2017-11-08
Last updated: 2024-05-17
Results posted: 2024-05-17

Locations

3 sites across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT03337087. Inclusion in this directory is not an endorsement.