Integration of Cetuximab, in Combination With Local Radiotherapy, in Perioperative Chemotherapy of Resectable and Locally Advanced Gastric Cancer. A Pilot Phase Ib-trial
• To determine the maximum tolerated dose of radio-chemo-immunotherapy - in patients with
localized or locally advanced gastric cancer
- To determine the efficacy, as measured by major histopathological response rates (tumor
regression grade 1 and 2)
- Metabolic response
- Secondary resectability
- R-0 resection rate
- Surgical morbidity
- Overall survival
- Time to local and systemic progression after R0-resection
OUTLINE: Prospective, multicenter, open-label dose escalating phase Ib trial
During induction chemo-immuno-therapy, patients receive cetuximab IV over 1-2 hours on days
1, cisplatin IV over 1 hour on day 1 and capecitabine twice daily per os from the evening of
day 1 to the morning of day 15. Treatment repeats every 3 weeks for up to 3 courses in the
absence of disease progression or unacceptable toxicity.
Radiotherapy will start after the end of the third cycle of chemotherapy and be performed
concomitantly with weekly cetuximab and cisplatin.
Cohorts of 3-6 patients receive escalating doses of radiotherapy (levels of 36/39.6/45 Gy)
until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
preceding that at which maximum 3 of 12 patients experience dose-limiting toxicity.
Gastric resection should be performed within 4-6 weeks after completion of neoadjuvant
4-6 weeks after surgery, a further 3 cycles of chemo-immuno-therapy will be administered if
the patient has recovered from surgery and the treatment is considered as feasible by the
For note: Cisplatin may be replaced by oxaliplatin during induction chemotherapy and
postoperative chemotherapy. In case if oxaliplatin is used to replace cisplatin during
induction chemotherapy, replacement of cisplatin by oxaliplatin during
radio-chemo-immunotherapy may also be considered by the investigator.
Capecitabine may be replaced by infusional 5-FU on day 1-5 every 21 days in case of
contraindications to capecitabine.
In case if both cisplatin and capecitabine are to be replaced, 4 cycles of FOLFOX-6 (d-l
leucovorin, followed by 5-FU bolus and a continuous infusion of over 46 hours every 2 weeks
should be administered in combination with cetuximab).
Patients undergo tumor tissue and blood sample collection periodically for biological
studies. Samples are analyzed for major histopathological response.
After completion of study treatment, patients are followed periodically for at least 5
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Dose limiting toxicity
Patients will be evaluated for dose limiting toxicities until four weeks after combined radio-chemo-immunotherapy
Anna Dorothea Wagner, MD
Centre Hospitalier Universitaire Vaudois