Liposomal Irinotecan, Fluorouracil, Leucovorin Calcium, and Rucaparib in Treating Patients With Metastatic Pancreatic, Colorectal, Gastroesophageal, or Biliary Cancer
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|ClinicalTrials.gov Identifier: NCT03337087|
Recruitment Status : Recruiting
First Posted : November 8, 2017
Last Update Posted : May 13, 2020
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Biliary Tract Carcinoma Metastatic Colorectal Carcinoma Metastatic Gastroesophageal Junction Adenocarcinoma Metastatic Malignant Digestive System Neoplasm Metastatic Pancreatic Adenocarcinoma Stage IV Colorectal Cancer AJCC v7 Stage IV Pancreatic Cancer AJCC v6 and v7 Stage IVA Colorectal Cancer AJCC v7 Stage IVB Colorectal Cancer AJCC v7||Drug: Fluorouracil Other: Laboratory Biomarker Analysis Drug: Leucovorin Calcium Drug: Liposomal Irinotecan Drug: Rucaparib||Phase 1 Phase 2|
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 both unselected and selected for BRCA 1/2 and PALB2 mutations (=< 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/leucovorin calcium (LV) with rucaparib (MFR). (Phase II)
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/LV with rucaparib (MFR). (Phase II) II. To assess the toxicity of the combination of nal-IRI and 5-FU/LV 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)
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.
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.
After completion of study treatment, patients are followed up every 6 months for 3 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||110 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of Irinotecan Liposome (Nal-IRI), Fluorouracil, Leucovorin 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)|
|Actual Study Start Date :||November 2, 2018|
|Estimated Primary Completion Date :||November 7, 2020|
|Estimated Study Completion Date :||November 7, 2021|
Experimental: Treatment (nal-IRI, leucovorin, fluorouracil, rucaparib)
Patients receive liposomal irinotecan IV over 90 minutes, leucovorin calcium IV, 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.
Other: Laboratory Biomarker Analysis
Drug: Leucovorin Calcium
Drug: Liposomal Irinotecan
- Number of participants with dose limiting toxicities (Phase I) [ Time Frame: Up to 28 days from start of treatment ]Will be assessed to determine maximum tolerated dose (MTD) of the combination of liposomal irinotecan (nal-IRI) and fluorouracil (5FU) with rucaparib (MFR). MTD is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients (at least 2 of a maximum of 6 new patients). A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD.
- Objective response (Phase Ib) [ Time Frame: Baseline up to 3 years ]Will evaluate changes in size of target lesions according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease.
- Best response rate (Phase II) [ Time Frame: At 32 weeks ]Will be defined as the number of patients who had response =< 32 weeks of registration divided by the number of evaluable patients. Response is defined as either complete response (CR) or partial response (PR), per RECIST 1.1.
- Disease control rate (DCR) [ Time Frame: Up to 3 years ]Will be defined as achieving complete response (CR), partial response (PR), or maintaining stable disease (per RECIST version 1.1) as the tumor assessment result for at least 24 weeks. DCR will be estimated by the number of evaluable patients achieving disease control divided by the total number of evaluable patients. Point estimates will be generated for disease control rates within each cohort along with 95% binomial confidence intervals.
- Overall survival (Phase II) [ Time Frame: Time from registration to death due to any cause, assessed up to 3 years ]Will be estimated using the method of Kaplan-Meier.
- Progression-free survival (Phase II) [ Time Frame: Time from registration to the earliest date documentation of disease progression or death due to any cause, assessed up to 3 years ]The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.
- Incidence of adverse events (Phase II) [ Time Frame: Up to 3 years ]Will be assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. The overall adverse event rates for grade 3 or higher adverse events will be compared using Chi-square or Fisher's exact tests between the two treatment groups.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03337087
|United States, Arizona|
|Mayo Clinic in Arizona||Recruiting|
|Scottsdale, Arizona, United States, 85259|
|Contact: Laurie A. Mihalik 480-342-3256 firstname.lastname@example.org|
|Principal Investigator: Tanios S. Bekaii-Saab|
|United States, Georgia|
|Emory University Hospital/Winship Cancer Institute||Recruiting|
|Atlanta, Georgia, United States, 30322|
|Contact: Christina S. Wu 404-778-0202 email@example.com|
|Principal Investigator: Christina S. Wu|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Contact: Lori L. Henrichs 507-538-8059 firstname.lastname@example.org|
|Principal Investigator: Wen Wee MA|
|United States, Utah|
|Huntsman Cancer Institute/University of Utah||Withdrawn|
|Salt Lake City, Utah, United States, 84112|
|Principal Investigator:||Tanios S Bekaii-Saab||Academic and Community Cancer Research United|