Phase II Trial of Erlotinib in Advanced Pancreatic Cancer

Inclusion Criteria

• •Patients must have histologically or cytologically confirmed pancreatic carcinoma that is locally advanced, unresectable or metastatic.
• •Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan.
• •Previous therapy:
• •Surgery: Previous surgery is permissible. Patients must be \> 4 weeks from any major surgery.
• •Chemotherapy: Patients may have received up to 1 prior line of gemcitabine based systemic therapy (single agent or combination therapy) for locally advanced or metastatic disease. Prior therapy with inhibitors of angiogenesis is permitted. All toxicities must be resolved to \< Grade 1 (CTCAE v 3.0) and the last dose must have been given at least 4 weeks prior to randomization.
• •Patients may also have received prior 5 FU (+/- folinic acid) or gemcitabine given concurrently with radiation as a "radiation sensitizer". All toxicities must be resolved and the last dose of chemotherapy must have been given at least 4 weeks prior to randomization.
• •Radiation: Patients may have received prior radiation treatment for management of local disease providing that disease progression has been documented (either locally or systemically), all toxicities have resolved, and the last fraction of radiation treatment was completed at least 4 weeks prior to randomization.
• •Age \>18 years. Because no dosing or adverse event data are currently available on the use of erlotinib in patients \<18 years of age, children are excluded from this study but will be eligible for future pediatric single-agent trials, if applicable.
• •Life expectancy of greater than or equal to 3 months.
• •ECOG performance status \<2.
• •Patients must have normal organ and marrow function as defined below:
• •* Leukocytes \>/= 3,000/mcL
• •* Absolute neutrophil count \>/= 1,000/mcL
• •* Platelets \>/= 100,000/mcL
• •* Total bilirubin \</= 1.5 UNL
• •* AST(SGOT) \</= 2.5 X institutional upper limit of normal
• •* INR \</= 1.5 unless on warfarin (see 3.1.9)
• •* Creatinine within normal institutional limits OR
• •* Creatinine clearance \>/= 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
• •Since CYP3A4 appears to be the major enzyme responsible for the human hepatic metabolism of erlotinib in vitro, the concurrent use of inhibitors and inducers of CYP3A4 are prohibited during the study treatment period. Concurrent use of CYP3A4 substrates are allowed, however, use caution and monitor the patient for potential drug interactions.
• •There is a potential interaction between erlotinib and warfarin. Patients have experienced elevated INRs and bleeding with this combination of drugs. Patients on warfarin with PT INR \>1.5 are eligible provided that all of the following criteria are met:
• •The patient is therapeutic on a stable dose of warfarin
• •The upper target for INR is no greater than 3.
• •The patient has no active bleeding or pathological condition that carries a high risk of bleeding (e.g., CT evidence of tumor invading the duodenum or known varices).
• •Note: anticoagulation with low molecular weight heparin is permitted.
• •The effects of erlotinib 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; 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.
• •Ability to understand and the willingness to sign a written informed consent document.