Capecitabine/Erlotinib Followed of Gemcitabine Versus Gemcitabine/Erlotinib Followed of Capecitabine

Randomized Phase III Trial With Capecitabine/Erlotinib Followed of Gemcitabine Versus Gemcitabine/Erlotinib Followed of Capecitabine in Patients With Advanced Pancreatic Cancer

This crossover trial is performed in advanced and metastatic pancreatic cancer not previously exposed to chemotherapy. The study compares a standard arm with gemcitabine plus erlotinib to an experimental arm with capecitabine plus erlotinib. It is the first trial of its kind to incorporate second-line treatment into the study design. Patient who fail on first-line therapy are switched to the comparator chemotherapy without erlotinib. The trial therefore not only compares two different regimens of first-line treatment, it also compares two sequential treatment strategies.

Inclusion Criteria:

• Age between 18 and 75 years
• Histologically proven pancreatic cancer stage III or IV (T1-3 N1M0 or T1 3N0 1M1)
• No option for resection with curative intent
• At least one measurable or not measurable lesion (according to RECIST)
• No previous chemotherapy or other systemic tumor therapy
• No previous radiation
• Performance-Status 0-2 according to WHO/ECOG
• Life expectancy of at least 3 months
• Adequate kidney-, liver- and bone marrow function, defined as
• Absolute neutrophil count * 1,5 x 109/l
• Hemoglobin * 8 g/dl
• Thrombocytes * 100 x 109/l
• Bilirubin * 2 x upper norm (with liver mets < 5-fold)
• Serum Creatinine * 1,25 x upper norm
• Creatinine clearance > 30 ml/min (Cockroft/Gault)
• Transaminases * 2,5 x upper norm (with liver mets < 5-fold)
• Possibility of regular long-term follow-up
• Negative pregnancy test in women at childbearing age
• All patients must have signed an informed consent before study entry.

Exclusion Criteria:

• Known secondary cancer other than curatively treated basalioma or carcinoma in situ of the cervix uteri
• Clinically unstable CNS-metastases
• Known hypersensitivity against study medication
• Severe impairment of renal function (creatinine clearance < 30 ml/min)
• Severe impairment of liver function (bilirubin > 2,0 x above upper norm, transaminases > 2,5 x upper norm, or with known liver metastasis >5 x upper norm)
• Clinically relevant disease of the cardiovascular system or other vital organs
• Known polyneuropathy
• Known DPD-deficiency (screening not required)
• Simultaneous treatment with the antiviral agent sorivudin or chemically related agents such as brivudin
• Pregnancy, lactation or lack of reliable contraception in women at childbearing age
• Mental disease, drug- or alcohol abuse
• Participation in another clinical trial within the last 4 weeks
• All other diseases which may prevent adequate participation in the trial
• Indication of lack of compliance with study regulations