Gemcitabine/Cisplatin +/-Cetuximab in Patients With Locally Advanced or Metastatic EGFR-Positive Pancreatic Cancer (SPaCe-01)

This is multicenter, open-label, randomized, phase II trial in patients with locally advanced or metastatic pancreatic cancer. Primary objective: objective response rate. Secondary objectives: safety, time to disease progression, median duration of response, time to treatment failure, overall survival time, correlation between bio-pathological characterization (EGFR, akt, MAPks) objective response and survival

During the last years, the esocrine pancreatic carcinoma presented a slow but constant increase of incidence. Chemotherapy determined disappointing results. Gemcitabine determined a slight advantage in survival and clinical benefit in comparison with gemcitabine with cisplatin or oxaliplatin Elevated expression of EGFR or its ligand correlates with worse prognosis in a variety of human cancers including pancreatic cancer. Therefore, blockade of EGFR activity would provide a novel strategy for the treatment of cancer. Cetuximab (C225) is a human/murine chimeric monoclonal antibody directed to the EGFR binding site. In a preclinical setting, Cetuximab has demonstrated anticancer activity both in cell culture experiments and in "in vivo" tumor xenograft animal model Since the combination of gemcitabine and cisplatin seems to be the more effective treatment for advanced pancreatic cancer and Cetuximab may improve activity of this combination we designed this phase II randomised trial to assess the role of Cetuximab in combination with gemcitabine and cisplatin in pancreatic cancer.

Inclusion Criteria:

• Age ≥ 18 years
• Histologically confirmed diagnosis of adenocarcinoma of the pancreas
• Locally advanced (non-resectable) or metastatic pancreatic cancer
• Presence of at least one uni-dimensional indicator lesion measurable by CT scan or MRI in not an irradiated area (RECIST criteria)
• Immunohistochemical evidence or positive EGFR expression prior to study entry in primary tumor and/or at least one metastasis
• Life expectancy of ≥ 3 months
• Karnofsky performance status of ≥70 at study entry
• Neutrophils ≥ 1.5 x 109/L, platelets ≥100 x 109/L, and hemoglobin ≥ 9 g/dL
• Bilirubin level either normal or < 1.5 x ULN
• ASAT and ALAT ≤ 2.5 X ULN (≤ 5 x ULN if liver metastasis are present)
• Serum creatinine < 1.5 x ULN
• Effective contraception for both, male and female patients if the risk of conception exists
• Signed written informed consents prior to beginning protocol specific procedures

Exclusion Criteria:

• Brain metastasis
• Previous chemotherapy for locally advanced or metastatic pancreatic cancer
• Adjuvant therapy is allowed if recurrence is documented > 6 months after the end of adjuvant treatment
• Radiotherapy within 4 weeks prior to study entry
• Concurrent chronic systemic immune therapy
• Any investigational agent(s) 4 weeks prior to entry
• Previous exposure to EGF, monoclonal antibodies, signal transduction inhibitors or EGFR targeting therapy
• Clinically relevant coronary artery disease or a history of a myocardial infarction within the last 12 months
• Known grade 3 or 4 allergic reaction to any of the components of the treatment
• Known drug abuse/ alcohol abuse
• Legal incapacity or limited legal capacity
• Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent
• Women who are pregnant or breastfeeding
• Any concurrent malignancy other than non-melanoma skin cancer, or carcinoma in situ of the cervix. (Patients with a previous malignancy but without evidence of disease for ≥ 5 years will be allowed to enter the trial).