Open, Randomized, Multicenter Phase II Trial With Cetuximab /5-FU/FA/Irinotecan or Cetuximab/5-FU/FA /Irinotecan/Oxaliplatin in K-ras/B-raf Wild Type Patients or With Irinotecan/Oxaliplatin/5-FU/FA With or Without Bevacizumab in K-ras Mutant Patients as Neoadjuvant Treatment in Patients With Non- Resectable Colorectal Liver Metastases.
Patients with liver metastases from colorectal and without known extrahepatic metastases
will be screened for this study. During screening, tumour blocks and blood samples will be
sent for central diagnostic of k-ras/b-raf and UGT1A1 status. B-raf mutant patients are not
treated within the trial.
Patients receive chemotherapy according to the allocation and are re-evaluated for
resectability every 8 weeks for a maximum of 6 months. Resectable patients will be resected
and receive an adjuvant treatment to complete 12 cycles. In circumstances detailed in the
protocol, a second resection is allowed within the study.
Patients will be randomized using a web-based computer system that allows randomization if
the key basic characteristics are entered.
Patients with k-ras and b-raf wild-type tumours will be randomized to receive:
- Cetuximab/FOLFIRI or
Patients with k-ras mutations will be randomized to receive:
- FOLFOXIRI or
Chemotherapy doses are adjusted to the risk of toxicity in all treatment arms.
Stratification will be performed according to:
- Number of metastases (< 5 vs. ≥ 5 metastases)
- Primary tumour in situ
For dose reductions and conditions to continue please refer to the full protocol. All drugs
are used within the label and approved doses.
Patients are evaluated for response by the same imaging technique as at baseline every 8
weeks. The findings will be discussed for resectability within two weeks after tumour
assessment in a local multidisciplinary team.
Technically resectable patients should be offered liver resection. The treatment will
continue until liver resection or for a maximum of six months (12 cycles).
After liver resection, an adjuvant treatment is recommended with the same schedule as
preoperatively, for a maximum combined pre- and postoperative treatment of 12 cycles. If
less than three postoperative cycles remain, no postoperative treatment will be started.
After resection, patients will be followed up for 5 years after randomization. This includes
- imaging and clinical investigation every three months for the first 2 years, then every
six months (patients without tumour progression / recurrence)
- survival status and surgical/medical treatment every three months for the first 2 years
and then every six months (all patients).
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Rate of patients with partial or complete response according to modified RECIST criteria.
up to 1 year after randomization
Gunnar Folprecht, PD Dr.
University hospital "Carl Gustav Carus" Dresden