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A Genotype-guided Dosing Study of mFOLFIRINOX in Previously Untreated Patients With Advanced Gastrointestinal Malignancies

Phase 1
18 Years
Open (Enrolling)
Acinar Cell Adenocarcinoma of the Pancreas, Adenocarcinoma of the Gallbladder, Adenocarcinoma of Unknown Primary, Adult Primary Cholangiocellular Carcinoma, Advanced Adult Primary Liver Cancer, Cholangiocarcinoma of the Extrahepatic Bile Duct, Cholangiocarcinoma of the Gallbladder, Diffuse Adenocarcinoma of the Stomach, Duct Cell Adenocarcinoma of the Pancreas, Intestinal Adenocarcinoma of the Stomach, Localized Unresectable Adult Primary Liver Cancer, Metastatic Carcinoma of Unknown Primary, Metastatic Extrahepatic Bile Duct Cancer, Mixed Adenocarcinoma of the Stomach, Mucinous Adenocarcinoma of the Colon, Mucinous Adenocarcinoma of the Rectum, Newly Diagnosed Carcinoma of Unknown Primary, Signet Ring Adenocarcinoma of the Colon, Signet Ring Adenocarcinoma of the Rectum, Stage III Pancreatic Cancer, Stage IIIA Colon Cancer, Stage IIIA Gallbladder Cancer, Stage IIIA Gastric Cancer, Stage IIIA Rectal Cancer, Stage IIIB Colon Cancer, Stage IIIB Gallbladder Cancer, Stage IIIB Gastric Cancer, Stage IIIB Rectal Cancer, Stage IIIC Colon Cancer, Stage IIIC Gastric Cancer, Stage IIIC Rectal Cancer, Stage IV Gastric Cancer, Stage IV Pancreatic Cancer, Stage IVA Colon Cancer, Stage IVA Gallbladder Cancer, Stage IVA Rectal Cancer, Stage IVB Colon Cancer, Stage IVB Gallbladder Cancer, Stage IVB Rectal Cancer, Unresectable Extrahepatic Bile Duct Cancer

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Trial Information

A Genotype-guided Dosing Study of mFOLFIRINOX in Previously Untreated Patients With Advanced Gastrointestinal Malignancies


I. To determine the dose-limiting toxicity (DLT) rate in cycle #1 in each of two UGT1A1
genotype groups (*1*1, *1*28) using genotype-guided dosing of irinotecan as part of the
modified (m) FOLFIRINOX regimen.


I. To determine the cumulative dose intensity of irinotecan achieved in each genotype group.

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


Patients receive oxaliplatin intravenously (IV) over 2 hours, irinotecan hydrochloride IV
over 1.5 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46
hours on days 1 and 15. Treatment repeats every 4 weeks for up to 6 courses in the absence
of disease progression or unacceptable toxicity.

Inclusion Criteria:

- Histologically or cytologically confirmed locally advanced or metastatic pancreatic
adenocarcinoma, colorectal 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 mFOLFIRINOX
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) >= l500/ul,

- Hemoglobin >= 9g/dL,

- Platelets >= 100,000/ ul,

- Total bilirubin < 1.5 x upper limit of normal,

- Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate
transaminase (SGPT) < 2.5 x upper limit of normal for patients without liver
metastases OR SGOT and SGPT < 5 x upper limit of normal for patients with liver

- Creatinine =< 1.5 x upper limit of normal,

- Measurable or non-measurable disease will be allowed,

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation, up until 30 days after final study
treatment; should a woman become pregnant or suspect that she is pregnant while
participating in this study, she should inform her treating physician immediately,

- Patients taking substrates, inhibitors, or inducers of Cytochrome P450 3A4 (CYP3A4)
should be encouraged to switch to alternative drugs whenever possible, given the
potential for drug-drug interactions with irinotecan

- 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, v. 4.0); pancreatic cancer patients with
clinical evidence of pancreatic insufficiency must be taking pancreatic enzyme

- 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

- 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

- Patients with any polymorphism in UGT1A1 other than *1 or *28.

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

DLT rate in course 1 for each of the two most common genotype groups (*1*1 and *1*28)

Outcome Description:

To show that the DLT rate is less than 33% with at least 70-80% confidence, which is comparable to the standard 3+3 phase I design with 0 out of 3 or 1 out of 6 patients experiencing a DLT.

Outcome Time Frame:

4 weeks

Safety Issue:


Principal Investigator

Hedy Kindler

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Chicago Comprehensive Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

March 2012

Completion Date:

March 2014

Related Keywords:

  • Acinar Cell Adenocarcinoma of the Pancreas
  • Adenocarcinoma of the Gallbladder
  • Adenocarcinoma of Unknown Primary
  • Adult Primary Cholangiocellular Carcinoma
  • Advanced Adult Primary Liver Cancer
  • Cholangiocarcinoma of the Extrahepatic Bile Duct
  • Cholangiocarcinoma of the Gallbladder
  • Diffuse Adenocarcinoma of the Stomach
  • Duct Cell Adenocarcinoma of the Pancreas
  • Intestinal Adenocarcinoma of the Stomach
  • Localized Unresectable Adult Primary Liver Cancer
  • Metastatic Carcinoma of Unknown Primary
  • Metastatic Extrahepatic Bile Duct Cancer
  • Mixed Adenocarcinoma of the Stomach
  • Mucinous Adenocarcinoma of the Colon
  • Mucinous Adenocarcinoma of the Rectum
  • Newly Diagnosed Carcinoma of Unknown Primary
  • Signet Ring Adenocarcinoma of the Colon
  • Signet Ring Adenocarcinoma of the Rectum
  • Stage III Pancreatic Cancer
  • Stage IIIA Colon Cancer
  • Stage IIIA Gallbladder Cancer
  • Stage IIIA Gastric Cancer
  • Stage IIIA Rectal Cancer
  • Stage IIIB Colon Cancer
  • Stage IIIB Gallbladder Cancer
  • Stage IIIB Gastric Cancer
  • Stage IIIB Rectal Cancer
  • Stage IIIC Colon Cancer
  • Stage IIIC Gastric Cancer
  • Stage IIIC Rectal Cancer
  • Stage IV Gastric Cancer
  • Stage IV Pancreatic Cancer
  • Stage IVA Colon Cancer
  • Stage IVA Gallbladder Cancer
  • Stage IVA Rectal Cancer
  • Stage IVB Colon Cancer
  • Stage IVB Gallbladder Cancer
  • Stage IVB Rectal Cancer
  • Unresectable Extrahepatic Bile Duct Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Carcinoma
  • Colonic Neoplasms
  • Rectal Neoplasms
  • Cystadenocarcinoma
  • Liver Neoplasms
  • Stomach Neoplasms
  • Pancreatic Neoplasms
  • Gallbladder Neoplasms
  • Bile Duct Neoplasms
  • Carcinoma, Acinar Cell
  • Cholangiocarcinoma
  • Neoplasms, Unknown Primary



University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470
Evanston CCOP-NorthShore University HealthSystemEvanston, Illinois  60201