Genetic Analysis-Guided Dosing of FOLFIRABRAX in Treating Patients With Advanced Gastrointestinal Cancer
A Genotype-Guided Dosing Study of FOLFIRABRAX in Previously Untreated Patients With Advanced Gastrointestinal Malignancies
3 other identifiers
interventional
50
1 country
8
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Dec 2014
Typical duration for phase_1
8 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 2014
CompletedFirst Submitted
Initial submission to the registry
January 5, 2015
CompletedFirst Posted
Study publicly available on registry
January 7, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2017
CompletedMay 31, 2023
May 1, 2023
3 years
January 5, 2015
May 26, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
DLT rate in course 1 for each of the three genotype groups, graded according to NCI CTCAE v 4.0
4 weeks
Secondary Outcomes (3)
Incidence of adverse events graded according to NCI CTCAE v 4.0
Up to 6 months
Response rates (by RECIST 1.1) for patients with each different type of gastrointestinal malignancy
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
Up to 6 months
Study Arms (1)
Treatment (FOLFIRABRAX)
EXPERIMENTALPatients 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.
Interventions
Given IV
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Chicagolead
- National Cancer Institute (NCI)collaborator
Study Sites (8)
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Decatur Memorial Hospital
Decatur, Illinois, 62526, United States
NorthShore University Health System
Evanston, Illinois, 60201, United States
Ingalls Memorial Hospital
Harvey, Illinois, 60426, United States
Fort Wayne Medical Oncology/Hematology
Fort Wayne, Indiana, 46845, United States
Indiana University Medical Center
Indianapolis, Indiana, 46202, United States
The University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109, United States
Virginia Mason
Seattle, Washington, 98101, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Manish Sharma
University of Chicago Comprehensive Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 5, 2015
First Posted
January 7, 2015
Study Start
December 1, 2014
Primary Completion
December 1, 2017
Study Completion
December 1, 2017
Last Updated
May 31, 2023
Record last verified: 2023-05