CALIVER (Colorectal Cancer Aflibercept in LIVER only metastases)
Research type
Research Study
Full title
A multicentre randomised phase II study of aflibercept plus chemotherapy in patients with colorectal liver-only metastases deemed to be inoperable or unsuitable for upfront liver resection
IRAS ID
140816
Contact name
Ian Chau
Contact email
Sponsor organisation
The Royal Marsden NHS Foundation Trust
Eudract number
2014-000845-64
Research summary
Colorectal cancer is one of the commonest cancers in the world. Although treatment options have improved in recent years, the outcome from un-resectable and/or metastatic colorectal cancer (mCRC)(i.e cancer with secondaries that have spread beyond the bowel) remains poor with high mortality and 5-year survival of less than 5%. Up to 50% of the patients with metastatic disease have colorectal liver metastases (CLM); 75-90% of the patients with CLM may not be able to have surgery due to the extent of their metastatic liver disease. Effective chemotherapy regimens utilising all the active chemotherapy drugs available in management of mCRC may enhance the liver resection rates and thus convert potentially un-resectable disease into resectable one; finally this may result in long-term disease control or even cure in a proportion of patients. Phase II studies have previously shown better overall response rate (ORR) when FOLFOXIRI regimen was used (Irinotecan, oxaliplatin and 5-FU).
Other studies have shown that tumours survive by having their own blood supply through a process called angiogenesis. One of the proven treatment strategies in management of mCRC includes using agents that can block the blood supply of the tumour (anti-angiogenic therapy). Aflibercept is a recombinant fusion protein that works by binding to vascular endothelial growth factor(VEGF) and placental growth factor(PIGF), which are the two important components in the angiogenic pathway.
Aflibercept has shown improvement in overall survival (OS) when used as second line therapy in combination with 5-FU and Irinotecan (FOLFIRI) in refractory mCRC patients in a randomised phase III study. CALIVER will be the first study defining the role of various combination therapies in patients with CLM, who were initially deemed unresectable. The study comprises of 1) safety run-in phase evaluating the optimal dose for aflibercept+FOLFOXIRI (9-12 patients) and 2) Main study (677 patients)
REC name
London - Riverside Research Ethics Committee
REC reference
14/LO/1673
Date of REC Opinion
14 Oct 2014
REC opinion
Favourable Opinion