Lapatinib Ditosylate and Capecitabine in Treating Patients With Metastatic Pancreatic Cancer

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas

• Measurable or non-measurable disease

  • Measurable disease is defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan
• No known brain metastases or leptomeningeal disease

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Life expectancy > 12 weeks
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL
• Albumin ≥ 2.5 g/dL
• Serum bilirubin ≤ 1.5 times upper limit of normal (ULN) (2.5 times ULN if Gilbert's syndrome is present)
• AST and ALT ≤ 3 times ULN (5 times ULN if documented liver metastases are present)
• Creatinine < 1.5 times ULN
• Cardiac ejection fraction normal by ECHO or MUGA scan
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to swallow and retain oral medication
• No gastrointestinal (GI) tract disease resulting in an inability to take oral medication, malabsorption syndrome, requirement for IV alimentation, or uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)
• No active hepatic or biliary disease, except for Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per investigator assessment

• No active cardiac disease within the past 6 months, including any of the following:

  • Uncontrolled angina
  • Clinically significant arrhythmia, except for asymptomatic atrial fibrillation requiring anticoagulation
  • Myocardial infarction
  • Uncontrolled or symptomatic congestive heart failure
  • Any other cardiac condition that, in the opinion of the treating physician, would make this study unreasonably hazardous for the patient
• No concurrent uncontrolled illness including, but not limited to, ongoing or active infection or psychiatric illness/social situation that would limit compliance with study requirements
• No known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to lapatinib ditosylate or any of its excipients, capecitabine, or fluorouracil
• No known dihydropyrimidine dehydrogenase (DPD) deficiency
• No other malignancy within the past 5 years except for completely resected nonmelanoma skin cancer or successfully treated in situ carcinoma

PRIOR CONCURRENT THERAPY:

• Recovered from prior radiotherapy or surgery
• No prior surgical procedures affecting absorption
• No prior EGFR- or ErbB2-targeting therapies
• No prior capecitabine
• No prior chemotherapy for locally advanced or metastatic pancreatic cancer

• At least 3 months since prior adjuvant chemotherapy

  • Prior fluorouracil allowed as a radiosensitizer only
• More than 30 days (or 5 half-lives) since prior investigational drugs
• No concurrent radiotherapy or surgery for metastatic cancer
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent CYP3A4 inducers or inhibitors
• No other concurrent investigational agents or anticancer therapy (e.g., cytotoxic or biologic therapy)
• No concurrent herbal (alternative) medicines