Open, Randomized, Multicenter, Randomized Phase II Trial Comparing the Combination of Cetuximab With Oxaliplatin/5-FU/FA Versus the Combination of Cetuximab With Irinotecan/5-FU/FA as Neoadjuvant Treatment in Patients With Non-Resectable Colorectal Liver Metastases
Patients with liver metastasis will be screened for this study. Eligible patients will
complete the pretreatment evaluation including an abdominal CT scan that will be presented
to the local surgeon and the radiologist for proving of resectability of hepatic lesions.
Additionally, CT scans will be reviewed by three reference surgeons. In case of
non-resectability, as defined above, CT- or ultrasound- guided biopsy of one of the liver
metastases will be performed, unless biopsy material is available from prior biopsy of one
of the liver metastases.
Instead of an ultrasound-guided biopsy, a CT-guided biopsy may be performed.
Formalin-fixed, paraffin embedded metastatic tissue will be sent to reference laboratory
(Prof. Störkel, Wuppertal) for immunohistochemical analysis of EGFR- expression.
Additionally tissue will be stored in "RNA later" for gene expression analysis if agreed by
Additionally, the primary tumor will be collected and sent to the reference laboratory for
analysis of EGFR- expression (if agreement of the patient exists).
Patients will be randomized to a combination of:
Cetuximab/FOLFIRI (irinotecan/5-FU/FA) or Cetuximab/FOLFOX6 (oxaliplatin/5-FU/FA)
All patients receive a four month treatment (eight cycles) of the allocated treatment.
Resection is planned after completion of neoadjuvant treatment and should be performed
between 4 and 6 weeks after the last dose of chemotherapy. Probes of the resected material
(in liquid nitrogen and paraffin embedded material will be collected).
If a resection is not possible after eight administrations of chemotherapy, chemotherapy
will be continued until tumor progression (maximal duration of treatment 2 years) and the
patient will be evaluated for a potential resection every two months.
After resection, postoperative treatment is planned for 3 months (6 cycles). Treatment start
is planned between 4 and 8 weeks after the operation.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Tumor response, defined as partial and complete response according to RECIST (Response Evaluation Criteria in Solid Tumors) - criteria in the intention-to-treat [ITT-] population
Claus-Henning Köhne, Prof. Dr.
Klinikum Oldenburg GmbH, Dr.-Eden-Str.10; 26133 Oldenburg