Name of the study
Treatment strategies in colorectal cancer patients with initially unresectable liver-only metastases CAIRO5 a randomized phase 3 study of the Dutch Colorectal Cancer Group (DCCG)
Researchers and contact information
Prof. dr. C.J.A. Punt, Prof. dr. T.M. van Gulik
Trial coordinator: K. Bolhuis
Academic Medical Center, IWO IA1-115
University of Amsterdam
1100 DE Amsterdam, The Netherlands
Colorectal cancer patients with unresectable liver-only metastases may be cured after downsizing of metastases by neoadjuvant systemic therapy. However, the optimal neoadjuvant induction regimen has not been defined, and the lack of consensus on criteria for (un)resectability complicates the interpretation of published results.
CAIRO5 is a multicentre, randomised, phase 3 clinical study. Colorectal cancer patients with initially unresectable liver-only metastases are eligible, and will not be selected for potential resectability. The (un)resectability status is prospectively assessed by a central panel consisting of at least one radiologist and three liver surgeons, according to predefined criteria. Tumours of included patients will be tested for RAS and BRAF mutation status and primary tumor location will be defined. Patients with RAS and BRAF wild type and left-sided colorectal tumours will be treated with doublet chemotherapy (FOLFOX or FOLFIRI) and randomised between the addition of either bevacizumab or panitumumab, and patients with RAS or BRAF mutant and/or right-sided primary colon tumours will be randomised between doublet chemotherapy (FOLFOX or FOLFIRI) plus bevacizumab or triple chemotherapy (FOLFOXIRI) plus bevacizumab. Radiological evaluation to assess conversion to resectability will be performed by the central panel, at an interval of two months.
The primary study endpoint is median progression-free survival. Secondary endpoints are the R0/1 resection rate, median overall survival, response rate, toxicity, pathological response of resected lesions, postoperative morbidity, and correlation of baseline and follow-up evaluation with respect to outcomes by the central panel.
RAS and BRAF wildtype AND left-sided primary tumor
Arm C: FOLFOX/FOLFIRI + bevacizumab
Arm D: FOLFOX/FOLFIRI + panitumumab
RAS or BRAF mutant and/or right-sided primary tumor
Arm A: FOLFOX/FOLFIRI + bevacizumab
Arm B: FOLFOXIRI + bevacizumab