A Phase II Study of Gemcitabine and Erlotinib As Adjuvant Therapy In Patients With Resected Pancreatic Cancer

• Overall survival [ Time Frame: 2-5 years ] [ Designated as safety issue: No ]
• Level of expression and mutation of EGFR and its downstream markers on tumor tissue and correlate with patient outcome. [ Time Frame: 1-2 years ] [ Designated as safety issue: No ]
• Serum levels of EGFR protein before and after administration of erlotinib and correlate with tumor recurrence and patient survival. [ Time Frame: 1-2 years ] [ Designated as safety issue: No ]

• To evaluate overall survival of patients with pancreatic cancer when treated with adjuvant erlotinib and gemcitabine.
• To evaluate level of expression and mutation of EGFR and its downstream markers on tumor tissue and correlate with patient outcome
• To evaluate the serum levels of EGFR protein before and after administration of erlotinib and correlate with tumor recurrence and patient survival.

Study Hypothesis: To estimate time to recurrence in pancreatic cancer patients treated with adjuvant erlotinib and gemcitabine. Combination therapy will be given for 4 months followed by single agent erlotinib for a total of 12 months.

PATIENT POPULATION Resected pancreatic cancer patients (R0 resection) within 10 weeks of surgery will be eligible, provided that they meet standard eligibility criteria.

STUDY DESIGN Phase II, open-label trial of erlotinib and gemcitabine. SAFETY PLAN Safety as assessed by CTCAE 3.0 STUDY TREATMENT Erlotinib 150 mg/day x 12 months. (oral) Gemcitabine 1500 mg/m2 IV over 150 minutes q 2 weeks x 4 months Patients will be monitored with serial CT scans for the first 2 years after completion of therapy.

Clinical Practice: Therapy will be administered as an outpatient. Primary Evaluations: Time to recurrence CONCOMITANT THERAPY AND CLINICAL PRACTICE No other anti-cancer therapy will be allowed while on study.

• Drug: Gemcitabine
  1500mg/m2 IV over 150 min IV q 2 weeks 4 months
  Other Name: Gemzar
• Drug: Erlotinib
  150 mg/d Daily, oral 12 months
  Other Name: Tarceva

Inclusion Criteria:

• Patients with potentially resectable pancreatic cancer (including ampullary cancer), prior to or after surgery will be accrued to this study.
• Patients who sign consent prior to surgery must have appropriate diagnostic imaging and be evaluated by one of the surgical co-investigators as having resectable disease, and probable pancreatic adenocarcinoma.
• Patients, who sign consent after surgery, must have adenocarcinoma of the pancreas with negative surgical margins.
• Adjuvant therapy should start within 10 weeks of surgery
• Age 18 years or older
• ECOG performance status of 0 - 1 (see Appendix A)
• Ability to take oral medications without difficulty
• Adequate bone marrow function as evidenced by an absolute neutrophil content (ANC) > 1500/mL and platelet count > 100,000/mL
• Adequate renal function as evidenced by serum creatinine within institutional limits or creatinine clearance > 50 ml/minute if above upper institutional limits (ULN)
• Adequate hepatic function as evidenced by ALT and total bilirubin within 2 times ULN.
• Provision of written informed consent.
• Men and women of childbearing potential must be willing to practice acceptable methods of birth control to prevent pregnancy.

Exclusion Criteria:

• Positive margins on post operative surgical specimen or evidence of metastatic disease (positive retroperitoneal margin is allowed)
• Biliary tree cancers are not allowed (Note: Ampullary cancer allowed).
• Known severe hypersensitivity to erlotinib or any of the excipients of these products
• Any prior treatment with radiation therapy or chemotherapy or vaccines for pancreatic cancer.
• Other coexisting malignancies or malignancies diagnosed within the last 3 years, with the exception of basal cell carcinoma or squamous cell carcinoma of the skin or cervical cancer in situ.
• Concomitant use of phenytoin, carbamazepine, barbiturates, rifampicin, phenobarbital, or St. John's Wort. Other agents which inhibit CYP3A4 may be used with caution (Appendix B)
• Treatment with a non-approved or investigational drug prior to treatment.
• Incomplete healing from previous oncologic or other major surgery.
• Pregnancy or breast feeding (women of childbearing potential).
• As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease).
• Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the trial.