A Trial of GW572016, Gemcitabine and Oxaliplatin for Metastatic Pancreaticobiliary Cancer Schema

Inclusion Criteria

• Patients are required to have histologically or pathologically confirmed, metastatic or locally advanced adenocarcinoma of the pancreas or biliary tree
• No prior systemic chemotherapy for locally advanced or metastatic pancreaticobiliary cancer. No prior EGFR inhibitors.
• ECOG performance status 0-2 retain ability to swallow oral medications
• Age > 18, non pregnant. Because no dosing or adverse event data are currently available on the use of GW572016 in patients <18 years of age, children are excluded from this study.
• The effects of GW572016 on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

A female is eligible to enter and participate in the study if she is of:

• Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who:
• Has had a hysterectomy,
• Has had a bilateral oophorectomy (ovariectomy),
• Has had a bilateral tubal ligation, or
• Is post-menopausal(a demonstration of total cessation of menses for ³1 year).
• Childbearing potential, has a negative serum pregnancy test at screening, and agrees to one of the following:
• Intrauterine Device (IUD),
• Vasectomized partner who is sterile prior to the female subject's entry and is the sole sexual partner for that female.
• Complete abstinence from sexual intercourse for two weeks before exposure to investigational products, throughout the clinical trial, and for at least one week after the last dose of investigational product.
• Double barrier contraception (condom with spermicidal jelly, foam, suppository, or film; diaphragm with spermicide; or male condom and diaphragm)
• Adequate hematologic function: ANC≥1500/ul,platelets≥100,000/ul,hemoglobin 8
• Adequate hepatic function with total bilirubin ≤ 1.5mg/dL and ALT or AST ≤ 2x ULN. (Patients with liver metastases may have AST/ALT less than or equal to 5x upper limit of normal). Patients with elevated bilirubin secondary to biliary obstruction that have subsequently been stented may enter the protocol with a bilirubin of < 2.0 as long as the bilirubin is falling.
• Adequate renal function: (creatinine ≤1.5mg/dL or estimated creatinine clearance greater than 60ml/min calculated by the Cockcroft Formula).
• Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram or MUGA scan. Note that baseline and on treatment scans should be performed using the same modality and preferably at the same institution.
• No peripheral neuropathy for patients who receive oxaliplatin.
• Life expectancy of at least 12 weeks
• Signed informed consent

Exclusion Criteria

A subject will not be eligible for inclusion in this study if any of the following criteria apply:

• Prior treatment with GW572016 or any EGFR targeting therapies.
• Prior treatment with systemic chemotherapy for metastatic pancreaticobiliary cancer.
• Evidence of brain metastases or leptomeningeal disease
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Known contraindications to the use of oxaliplatin or gemcitabine.
• History of allergy to platinum compounds in patients receiving oxaliplatin. Amendment #2 4/28/05
• The subject has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug.
• HIV-positive patients receiving combination anti-retroviral therapy are excluded from the s