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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

Phase 2
18 Years
Not Enrolling
Colorectal Cancer, Liver Metastases

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Trial Information

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
the patient.

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.

Inclusion Criteria:

- Patients with non-resectable, histologically confirmed, synchronous or metachronous
colorectal liver metastases. Patients with non-resectable metastases are defined as;
patients with five or more liver metastases; and/or patients with liver metastases
that are technically non-resectable (local surgeon in cooperation with local
radiologist will define non-resectability on the basis of remaining functional liver
tissue, infiltration of all liver veins, infiltration of both liver arteries, both
portal branches or both bile ducts).

- Patients with simultaneous liver metastases are eligible, if the primary tumor has
been resected at least 1 month prior to chemotherapy.

- Karnofsky Performance Status ≥ 80

- Informed consent

- Adequate bone marrow function, liver and renal function (neutrophils > 1.5 x 10^9/l;
thrombocytes > 100 x 10^9/l; hemoglobin > 8.0 g/l; bilirubin ≤ 1.5 x upper limit of
normal [ULN] and not increasing more than 25% within the last 4 weeks; ALAT and ASAT
< 5 x UNL; serum creatinine ≤ 1.5 x UNL)

- Age ≥ 18 years

Exclusion Criteria:

- Any evidence of extrahepatic metastases, lymph node metastases and primary tumor

- Prior chemotherapy (except adjuvant chemotherapy with an interval of ≥ 6 months)

- Previous exposure to EGFR (epidermal growth factor receptor)-targeting therapy

- Radiotherapy or major abdominal or thoracic surgery (excluding diagnostic biopsy or
port implantation) ≤ 4 weeks before study entry

- Concurrent systemic immune therapy, chemotherapy, or hormone therapy

- Investigational agents or participation in clinical trials within 30 days before
start of the treatment in study

- Clinically relevant coronary disease or myocardial infarction within 12 months before
study entry

- Peripheral neuropathy > CTC grade I

- Inflammatory bowel disease

- Previous malignancy (except colorectal cancer, history of basal cell carcinoma of
skin or pre-invasive carcinoma of the cervix with adequate treatment)

- History of severe psychiatric illness

- Drug or alcohol abuse

- Breast feeding or pregnant women, no effective contraception if risk of conception
exists (male and female patients)

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Principal Investigator

Claus-Henning Köhne, Prof. Dr.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Klinikum Oldenburg GmbH, Dr.-Eden-Str.10; 26133 Oldenburg


Germany: Paul-Ehrlich-Institut

Study ID:




Start Date:

November 2004

Completion Date:

Related Keywords:

  • Colorectal Cancer
  • Liver Metastases
  • Cetuximab
  • Oxaliplatin
  • Irinotecan
  • 5-FU
  • Chemotherapy
  • Resection
  • Liver resection
  • Neoadjuvant
  • Colorectal Neoplasms
  • Neoplasm Metastasis
  • Neoplasms, Second Primary
  • Liver Neoplasms