Oxaliplatin, Gemcitabine, Erlotinib, and Radiation Therapy in Treating Patients With Unresectable and/or Metastatic Pancreatic Cancer or Biliary Tract Cancer
Oxaliplatin, Gemcitabine, Erlotinib, and Radiation Therapy in Treating Patients With Unresectable and/or Metastatic Pancreatic Cancer or Biliary Tract Cancer
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and gemcitabine, work in different
 ways to stop the growth of tumor cells, either by killing the cells or by stopping them from
 dividing. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed
 for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving
 oxaliplatin together with gemcitabine, erlotinib, and radiation therapy may kill more tumor
 cells.

 PURPOSE: This phase I trial is studying the side effects and best dose of oxaliplatin,
 gemcitabine, and erlotinib when given together with radiation therapy in treating patients
 with unresectable and/or metastatic pancreatic cancer or biliary tract cancer.
OBJECTIVES:

 -  Determine the maximum tolerated dose (MTD) of oxaliplatin and gemcitabine hydrochloride
 when combined with radiotherapy in patients with unresectable and/or metastatic
 pancreatic or biliary tract adenocarcinoma. (Part 1)

 -  Determine the MTD of erlotinib hydrochloride and gemcitabine hydrochloride when combined
 with oxaliplatin at the MTD and radiotherapy in these patients. (Part 2)

 OUTLINE: This is a multicenter, nonrandomized, parallel group, uncontrolled, open-label,
 dose-escalation study of gemcitabine hydrochloride, oxaliplatin, and erlotinib hydrochloride.

 -  Part 1: Patients receive gemcitabine hydrochloride IV over 30-60 minutes and oxaliplatin
 IV on day 1. Patients also undergo external beam radiotherapy (EBRT) once daily on days
 1-5. Treatment repeats every 7 days for up to 6 courses.

 Cohorts of 3-6 patients receive escalating doses of gemcitabine hydrochloride and oxaliplatin
 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
 preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT). Up
 to 10 patients are treated at the MTD.

 -  Part 2: Patients receive gemcitabine hydrochloride, oxaliplatin*, and EBRT as in part 1.
 Patients also receive oral erlotinib hydrochloride once daily on days 1-5. Treatment
 repeats every 7 days for up to 6 courses.

 Cohorts of 3-6 patients receive escalating doses of gemcitabine hydrochloride and erlotinib
 hydrochloride until the MTD is determined. The MTD is defined as the dose preceding that at
 which 2 of 3 or 2 of 6 patients experience DLT. Up to 10 patients are treated at the MTD.

 NOTE: *Patients receive oxaliplatin at the MTD determined in part 1.

 After completion of study treatment, patients are followed every 3 months.
DISEASE CHARACTERISTICS:

 -  Biopsy confirmed diagnosis of any of the following:

 -  Pancreatic carcinoma

 -  Ampullary carcinoma

 -  Biliary tract (gallbladder or bile duct) carcinoma

 -  Unresectable and/or biopsy-proven metastatic disease

 -  Suitable for bimodality therapy, as determined by a medical oncologist and radiation
 oncologist

 PATIENT CHARACTERISTICS:

 -  ECOG performance status 0-2

 -  Life expectancy > 2 months

 -  ANC > 1,500/mm³

 -  Platelet count > 100,000/mm³

 -  Creatinine < 1.5 mg/dL

 -  Total bilirubin < 2 times upper limit of normal (ULN)

 -  AST < 3 times ULN (< 5 times ULN if liver metastases are present)

 -  Not pregnant or nursing

 -  Negative pregnancy test

 -  Fertile patients must use effective contraception

 -  No known hypersensitivity to platinum agent or gemcitabine hydrochloride

 -  No serious medical or psychiatric illnesses that would preclude giving informed
 consent

 PRIOR CONCURRENT THERAPY:

 -  No prior radiotherapy to the upper abdomen

 -  More than 3 weeks since prior chemotherapy

 -  No prior erlotinib hydrochloride

 -  At least 5 days since prior and no concurrent CYP3A4 inducer/inhibitor