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

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
metastases,

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