Safety of Combining Irinotecan With 5-FU, Leucovorin/Folinic Acid, Oxaliplatin, and Docetaxel Chemotherapies

Inclusion Criteria:

1. Histologically or cytologically confirmed locally advanced or metastatic pancreaticadenocarcinoma, gastroesophageal adenocarcinoma, cholangiocarcinoma, gallbladderadenocarcinoma, ampullary carcinoma, adenocarcinoma of unclear primary (with upperGI primary suspected), or other primary GI malignancy for which the treatingphysician feels that I-FLOAT is a reasonable therapeutic option.

2. Patients with a history of obstructive jaundice due to the primary tumor must haveresolved to <1.5 X upper limit of normal and a metal biliary stent in place

3. Age greater than or equal to 18 years.

4. Eastern Cooperative Oncology Group (ECOG) performance status =1

5. Life expectancy > 3 months

6. Adequate organ function, as defined by each of the following: Absolute neutrophil count (ANC) = 1500/uL Hemoglobin > 9g/dL (transfusion permittedwith stability for > 1 week) Platelets > 100,000/uL Total bilirubin = 1.5 mg/dL ASTand ALT = 2.5 X upper limit of normal; alkaline phosphatase = 2.5 X upper limit ofnormal, unless bone metastasis is present in the absence of liver metastasis. AST and ALT = 5 X upper limit of normal if hepatic metastases are present.Creatinine = 1.5 mg/dL

7. Measurable or non-measurable disease will be allowed.

8. Women of childbearing potential and sexually active males must use an effectivecontraception method during treatment and for three months after completingtreatment.

9. Negative serum or urine B-hCG pregnancy test at screening for patients ofchildbearing potential

10. Patients taking substrates, inhibitors, or inducers of CYP3A4 should be encouragedto switch to alternative drugs whenever possible, given the potential for drug-druginteractions with irinotecan.

Exclusion Criteria:

1. Prior radiation therapy for any cancer.

2. Prior chemotherapy for metastatic disease Recurrence of disease within 6 months ofperioperative chemotherapy are eligible if other eligibility criteria are met

3. Inflammatory bowel disease (Crohn's disease, ulcerative colitis)

4. Diarrhea, grade 1 or greater by the National Cancer Institute Common TerminologyCriteria for Adverse Events (NCI-CTCAE, v. 4.0*). Pancreatic cancer patients withclinical evidence of pancreatic insufficiency must be taking pancreatic enzymereplacement.

5. Neuropathy, grade 2 or greater by NCI-CTCAE, v. 4.0.

6. Documented brain metastases

7. Serious underlying medical or psychiatric illnesses that would, in the opinion ofthe treating physician, substantially increase the risk for complications related totreatment.

8. Active uncontrolled bleeding.

9. Pregnancy or breastfeeding.

10. Major surgery within 4 weeks.

11. Previous or concurrent malignancy, except for adequately treated basal cell orsquamous cell skin cancer, in situ cervical cancer, or any other cancer for whichthe patient has been previously treated and the lifetime recurrence risk is lessthan 30%, and meets all other eligibility criteria.