Tarceva and Capecitabine for Pancreatic Cancer

A Phase II Study of OSI-774 (Tarceva) in Combination With Capecitabine in Previously Treated Patients With Metastatic Pancreatic Cancer

This phase II trial is designed to investigate the effectiveness of Tarceva (OSI-774) combined with capecitabine in treating patients with metastatic pancreatic cancer.

Patients will be treated once daily with Tarceva, twice daily with capecitabine for 14 consecutive days, followed by 7 days off of capecitabine (a cycle is 21 days). At week 1 of each cycle a physical exam and blood work will be performed. Reassessment of tumor size will be conducted at 6 weeks (2 cycles), 12 weeks (4 cycles) and then every 9 weeks thereafter. Patients will remain on treatment until one of the following occur: disease progression, illness that prevents further treatment or unacceptable adverse events.

Inclusion Criteria:

• Metastatic pancreatic carcinoma (excluding pancreatic endocrine tumors)

• Only patients with measurable disease

• ECOG performance status < or equal to 1

• Life expectancy >12 weeks

• Signed informed consent

• Failed or intolerance to first-line therapy for metastatic disease with a gemcitabine-containing regimen. Patients may have received adjuvant therapy in addition to one prior regimen for metastatic disease.

• >4 weeks must have elapsed from the completion of previous chemotherapy and patients must have recovered from any related toxicities

• >4 weeks must have elapsed from the participation in any investigational drug study

• Laboratory values:

  • ANC > 1500/mm3;
  • Hemoglobin > 9.0 gm/dl;
  • Platelets > 100,000/mm3;
  • SGOT <2.5 X upper limit of normal; or <5 X upper limit of normal if evidence of liver metastases; Alkaline phosphatase < 2.5 X upper limit of normal; or < 5 X upper limit of normal if evidence of liver metastases; Total bilirubin < 1.5 X upper limit of normal; Creatinine clearance > 50 cc/min (by Cockroft - Gault or as determined from a 24-hour urine collection).

Exclusion Criteria:

• Prior therapy with capecitabine or epidermal growth factor receptor (EGFR) inhibitors
• More than one prior chemotherapy treatment regimen for metastatic disease
• Clinically apparent central nervous system (CNS) metastases or carcinomatous meningitis
• Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication or heart attack within the last 12 months).
• Major surgery within 4 weeks of the start of study treatment, without complete recovery.
• Evidence of CNS metastases (unless CNS metastases have been stable for > 3 months) or history of uncontrolled seizures, central nervous system disorders
• Uncontrolled serious medical or psychiatric illness
• Women must not be pregnant or lactating
• Concurrent radiation therapy
• Other active malignancy
• Inability to swallow tablets
• Patients lacking physical integrity of the upper gastrointestinal tract or who have malabsorption syndrome
• Prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity to 5-fluorouracil