Genetic Analysis-Guided Dosing of FOLFIRABRAX in Treating Patients With Advanced Gastrointestinal Cancer

May 26, 2023 updated by: University of Chicago

A Genotype-Guided Dosing Study of FOLFIRABRAX in Previously Untreated Patients With Advanced Gastrointestinal Malignancies

This phase I/II trial studies the side effects of genetic analysis-guided dosing of paclitaxel albumin-stabilized nanoparticle formulation, fluorouracil, leucovorin calcium, and irinotecan hydrochloride (FOLFIRABRAX) in treating patients with gastrointestinal cancer that has spread to other parts of the body and usually cannot be cured or controlled with treatment. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, fluorouracil, leucovorin calcium, and irinotecan hydrochloride, 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. Genetic analysis may help doctors determine what dose of irinotecan hydrochloride patients can tolerate.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the dose-limiting toxicity (DLT) rate in cycle #1 in each of three uridine diphosphate (UDP) glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) genotype groups (*1/*1, *1/*28, *28/*28) using genotype-guided dosing of irinotecan (irinotecan hydrochloride) as part of the FOLFIRABRAX regimen.

SECONDARY OBJECTIVES:

I. To determine the cumulative dose of each chemotherapy drug (nab-paclitaxel [paclitaxel albumin-stabilized nanoparticle formulation], irinotecan, 5-FU [fluorouracil]) administered in each genotype group.

II. To determine the response rates (in patients with measurable disease) by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) for each different disease (pancreatic cancer, biliary tract cancer, esophageal/gastric cancer, adenocarcinoma of unknown primary) treated in the study.

OUTLINE:

Patients receive FOLFIRABRAX comprising paclitaxel albumin-stabilized nanoparticle formulation intravenously (IV) over 0.5 hours, leucovorin calcium IV over 2 hours, irinotecan hydrochloride IV over 1.5 hours, and fluorouracil IV over 46 hours on days 1 and 15. Courses repeat every 4 weeks for up to 6 months in the absence of disease progression or unacceptable toxicity.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 1

Contacts and Locations

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

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Comprehensive Cancer Center
      • Decatur, Illinois, United States, 62526
        • Decatur Memorial Hospital
      • Evanston, Illinois, United States, 60201
        • NorthShore University Health System
      • Harvey, Illinois, United States, 60426
        • Ingalls Memorial Hospital
    • Indiana
      • Fort Wayne, Indiana, United States, 46845
        • Fort Wayne Medical Oncology/Hematology
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • The University of Michigan Comprehensive Cancer Center
    • Washington
      • Seattle, Washington, United States, 98101
        • Virginia Mason

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.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed locally advanced or metastatic pancreatic adenocarcinoma, gastric adenocarcinoma, cholangiocarcinoma, gall bladder adenocarcinoma, ampullary carcinoma, adenocarcinoma of unclear primary (with a gastrointestinal primary suspected), or other primary gastrointestinal malignancy for which the treating physician feels that FOLFIRABRAX is a reasonable therapeutic option
  • Patients with a history of obstructive jaundice due to the primary tumor must have a metal biliary stent in place
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1
  • Life expectancy > 3 months
  • Absolute neutrophil count (ANC) >= 1500/ul
  • Hemoglobin > 9 g/dL
  • Platelets > 100,000/ul
  • Total bilirubin =< 1.25 times upper limit of normal
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 times upper limit of normal
  • Alkaline phosphatase =< 2.5 times the upper limit of normal, unless bone metastasis is present in the absence of liver metastasis
  • Creatinine =< 1.5 mg/dL
  • Measurable or non-measurable disease will be allowed, but only those with measurable disease will be evaluable for the response rate endpoint
  • Women of childbearing potential and sexually active males must use an effective contraception method during treatment and for three months after completing treatment
  • Negative serum or urine beta human chorionic gonadotropin (beta-hCG) pregnancy test at screening for patients of childbearing potential
  • Signed informed consent

Exclusion Criteria:

  • Prior chemotherapy or radiation therapy for any cancer
  • Inflammatory bowel disease (Crohn's disease, ulcerative colitis)
  • Diarrhea, grade 1 or greater by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version [v.] 4.0); pancreatic cancer patients with clinical evidence of pancreatic insufficiency must be taking pancreatic enzyme replacement
  • Neuropathy, grade 2 or greater by NCI-CTCAE, v. 4.0
  • Documented brain metastases
  • Serious underlying medical or psychiatric illnesses that would, in the opinion of the treating physician, substantially increase the risk for complications related to treatment
  • Active uncontrolled bleeding
  • Pregnancy or breastfeeding
  • Major surgery within 4 weeks
  • Previous or concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or any other cancer for which the patient has been previously treated and the lifetime recurrence risk is less than 30%
  • Patients taking substrates, inhibitors and inducers of cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) should be encouraged to switch to alternative drugs whenever possible
  • Patients with any polymorphism in UGT1A1 other than *1 or *28 (e.g., *6)
  • History of interstitial lung disease, idiopathic pulmonary fibrosis, silicosis or connective tissue disorders
  • Subjects known to be human immunodeficiency virus (HIV)-positive, including those on combination antiretroviral therapy, are ineligible

Study Plan

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

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (FOLFIRABRAX)
Patients receive FOLFIRABRAX comprising paclitaxel albumin-stabilized nanoparticle formulation IV over 0.5 hours, leucovorin calcium IV over 2 hours, irinotecan hydrochloride IV over 1.5 hours, and fluorouracil IV over 46 hours on days 1 and 15. Courses repeat every 4 weeks for up to 6 months in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Fluorouracil
Given IV
Drug: Leucovorin Calcium
Given IV
Other Names:
  • CF
Drug: Irinotecan Hydrochloride
Given IV
Drug: Paclitaxel Albumin-Stabilized Nanoparticle Formulation
Given IV
Other Names:
  • ABI-007
  • Abraxane
  • ABI 007

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
DLT rate in course 1 for each of the three genotype groups, graded according to NCI CTCAE v 4.0
Time Frame: 4 weeks
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of adverse events graded according to NCI CTCAE v 4.0
Time Frame: Up to 6 months
Adverse events will be summarized by type, grade, and attribution.
Up to 6 months
Response rates (by RECIST 1.1) for patients with each different type of gastrointestinal malignancy
Time Frame: Up to 6 months
These results will be compared descriptively to appropriate historical controls. Exact 90% confidence intervals will be generated for the response rates.
Up to 6 months
Cumulative doses of the drugs will be calculated as the sum of all doses received on protocol therapy for each patient
Time Frame: Up to 6 months
The means and standard deviations for patients in each genotype group will be reported.
Up to 6 months

Collaborators and Investigators

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

Sponsor

University of Chicago

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Manish Sharma, University of Chicago Comprehensive Cancer Center

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 Major Dates

Study Start

December 1, 2014

Primary Completion (Actual)

December 1, 2017

Study Completion (Actual)

December 1, 2017

Study Registration Dates

First Submitted

January 5, 2015

First Submitted That Met QC Criteria

January 6, 2015

First Posted (Estimated)

January 7, 2015

Study Record Updates

Last Update Posted (Actual)

May 31, 2023

Last Update Submitted That Met QC Criteria

May 26, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB14-0595 (Other Identifier: University of Chicago Comprehensive Cancer Center)
  • P30CA014599 (U.S. NIH Grant/Contract)
  • NCI-2014-02407 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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