Efficacy of Cetuximab in Combination With Irinotecan and 5- FU/FA in Treatment of Metastatic Gastric Cancer

An Open-label, Non-randomized Phase II Trial of Cetuximab in Combination With Irinotecan and 5-FU/FA for Patients With Metastatic Gastric Cancer

Based on the current promising results with irinotecan and cetuximab in patients with recurrent metastatic colorectal cancer, and the excellent results of Irinotecan and 5-FU in gastric cancer , the present clinical study to evaluate the overall response rate, the time to progression and the overall survival of the combined treatment of cetuximab and irinotecan and 5-FU in patients with esophagogastric cancer is urgently needed.

Cetuximab will be analysed with biological markers

Inclusion Criteria:

Signed and dated informed consent before the start of specific protocol procedures;

• Histologically proven gastric adenocarcinoma including adenocarcinoma of the esophagogastric junction or Barrett carcinoma (adenocarcinoma of lower oesophagus);

• Measurable metastatic disease according to the RECIST criteria. If locally recurrent disease, it must be associated with at least one measurable lymph node (> 20 mm by CT scan or > 10 mm with spiral CT);

• Age: 18-75 years;

• ECOG Performance Status 0-2

• Life expectancy > 12 weeks;

• Adequate hematological, hepatic and renal functions: ANC

  ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L; hemoglobin ≥ 10g/dl; creatinine ≤ 2 x UNL; total bilirubin ≤ 3 x UNL, ASAT (SGOT) and ALAT (SGPT) ≤ 3 × UNL; in case of liver metastases: total bilirubin ≤ 5 x UNL, ASAT (SGOT) and ALAT (SGPT) ≤ 5 × UNL;

• At least 4 weeks from surgery;

• Recovery from side effects of any prior therapy;

• Able to comply with scheduled assessments and with management of toxicity.

• If of childbearing potential, willingness to use effective contraceptive method for the study duration and 2 months post-dosing.

Exclusion Criteria:

• Other tumor type than adenocarcinoma (e.g., leiomyosarcoma, lymphoma) or a second cancer except in patients with squamous or basal cell carcinoma of the skin or carcinoma in situ of the cervix which has been effectively treated. Patients curatively treated and disease free for at least 5 years will be discussed with the sponsor before inclusion;

  • Concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy not indicated in the study protocol;
  • Any prior palliative chemotherapy, adjuvant (and/or neoadjuvant) chemotherapy or radiotherapy ;
  • Concurrent treatment with any other anti-cancer therapy;
  • Patients with known brain or leptomeningeal metastasis;
  • Hypercalcemia not controlled by bisphosphonates;
  • Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection (> hemicolectomy or extensive small intestine resection with chronic diarrhea), Crohn's disease, ulcerative colitis;
  • Other serious illness or medical conditions:

• Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry; congestive heart failure NYHA grade 3 and 4;

• Current history of chronic diarrhea;

• History of significant neurologic or psychiatric disorders including dementia or seizures;

• Active uncontrolled infection;

• Active disseminated intravascular coagulation;

• Other serious underlying medical conditions which could impair the ability of the patient to participate in the study;

  • Known deficit in DPD
  • Contraindications to the use of atropine;
  • Concomitant or within a 4-week period administration of any other experimental drug under investigation;
  • Pregnant or lactating women;
  • Previous exposure to monoclonal antibodies, signal transduction inhibitors or EGFR pathway targeting therapy;
  • Known allergic/hypersensitivity reaction to any of the components of the treatment;
  • Known drug abuse/alcohol abuse.