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

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ClinicalTrials.gov Identifier: NCT02333188
Recruitment Status : Completed
First Posted : January 7, 2015
Last Update Posted : December 12, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Chicago

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.

Condition or disease Intervention/treatment Phase
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 Drug: Leucovorin Calcium Drug: Irinotecan Hydrochloride Drug: Fluorouracil Other: Laboratory Biomarker Analysis Phase 1 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Genotype-Guided Dosing Study of FOLFIRABRAX in Previously Untreated Patients With Advanced Gastrointestinal Malignancies
Study Start Date : December 2014
Actual Primary Completion Date : December 2017
Actual Study Completion Date : December 2017


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.
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




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

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02333188


Locations
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United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637
Decatur Memorial Hospital
Decatur, Illinois, United States, 62526
NorthShore University Health System
Evanston, Illinois, United States, 60201
Ingalls Memorial Hospital
Harvey, Illinois, United States, 60426
United States, Indiana
Fort Wayne Medical Oncology/Hematology
Fort Wayne, Indiana, United States, 46845
Indiana University Medical Center
Indianapolis, Indiana, United States, 46202
United States, Michigan
The University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
United States, Washington
Virginia Mason
Seattle, Washington, United States, 98101
Sponsors and Collaborators
University of Chicago
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Manish Sharma University of Chicago Comprehensive Cancer Center

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Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT02333188     History of Changes
Other Study ID Numbers: 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 )
First Posted: January 7, 2015    Key Record Dates
Last Update Posted: December 12, 2017
Last Verified: December 2017
Additional relevant MeSH terms:
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Adenocarcinoma
Pancreatic Neoplasms
Stomach Neoplasms
Cholangiocarcinoma
Gallbladder Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gastrointestinal Diseases
Stomach Diseases
Biliary Tract Neoplasms
Biliary Tract Diseases
Gallbladder Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Irinotecan
Fluorouracil
Calcium
Levoleucovorin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators