We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

This study is currently recruiting participants.
Verified July 2017 by University of Chicago
Sponsor:
ClinicalTrials.gov Identifier:
NCT02333188
First Posted: January 7, 2015
Last Update Posted: July 11, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Chicago
January 5, 2015
January 7, 2015
July 11, 2017
December 2014
November 2017   (Final data collection date for primary outcome measure)
DLT rate in course 1 for each of the three genotype groups, graded according to NCI CTCAE v 4.0 [ Time Frame: 4 weeks ]
Same as current
Complete list of historical versions of study NCT02333188 on ClinicalTrials.gov Archive Site
  • 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.
  • 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.
  • 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.
Same as current
Not Provided
Not Provided
 
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
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.

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.

Interventional
Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Adenocarcinoma of Unknown Primary
  • Adult Cholangiocarcinoma
  • Gallbladder Carcinoma
  • Gastric Adenocarcinoma
  • Malignant Gastrointestinal Neoplasm
  • Metastatic Pancreatic Adenocarcinoma
  • Pancreatic Adenocarcinoma
  • Stage III Ampulla of Vater Cancer
  • Stage III Pancreatic Cancer
  • Stage IIIA Gallbladder Cancer
  • Stage IIIA Gastric Cancer
  • Stage IIIB Gallbladder Cancer
  • Stage IIIB Gastric Cancer
  • Stage IV Ampulla of Vater Cancer
  • Stage IV Gallbladder Cancer
  • Stage IV Gastric Cancer
  • Stage IV Pancreatic Cancer
  • Drug: Paclitaxel Albumin-Stabilized Nanoparticle Formulation
    Given IV
    Other Names:
    • ABI 007
    • ABI-007
    • Abraxane
  • Drug: Leucovorin Calcium
    Given IV
    Other Name: CF
  • Drug: Irinotecan Hydrochloride
    Given IV
  • Drug: Fluorouracil
    Given IV
  • Other: Laboratory Biomarker Analysis
    Correlative studies
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.
Interventions:
  • Drug: Paclitaxel Albumin-Stabilized Nanoparticle Formulation
  • Drug: Leucovorin Calcium
  • Drug: Irinotecan Hydrochloride
  • Drug: Fluorouracil
  • Other: Laboratory Biomarker Analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
51
Not Provided
November 2017   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
United States
 
 
NCT02333188
IRB14-0595
NCI-2014-02407 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
IRB14-0595 ( Other Identifier: University of Chicago Comprehensive Cancer Center )
P30CA014599 ( U.S. NIH Grant/Contract )
No
Not Provided
Not Provided
University of Chicago
University of Chicago
National Cancer Institute (NCI)
Principal Investigator: Manish Sharma University of Chicago Comprehensive Cancer Center
University of Chicago
July 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP