Roche resumes recruitment to AVANT trial

Roche is to resume patient recruitment to its AVANT trial of different combination chemotherapies for post-surgical adjuvant treatment of colon cancer following the AVANT independent Data Safety Monitoring Board's (DSMB) recommendation that "the current safety profile and the death rates from all causes in AVANT were consistent with those seen in other adjuvant colon cancer trials".

The trial, a three-arm global study randomising high-risk stage II and stage III patients with colon cancer to assess the effect of adding Avastin to the chemotherapy regimens FOLFOX-4 or XELOX, was initially suspended in February 2006 because of the DSMB's concern over safety in Arm C (patients taking XELOX and Avastin), where seven deaths (1% of the trial population) had occurred either 'suddenly' or in 'younger patients'. Arm A (FOLFOX-4) had seen four deaths (0.6%) and Arm B (FOLFOX-4 and Avastin), had seen three (0.4%).

The fast recruitment in the trial was also seen as a cause for concern as it 'could prevent adequate and timely intervention'. Since it began recruitment in December 2004, almost two-thirds of the target number of 3,450 patients have been enrolled, with 250 joining in January 2006 alone.

Patients who had already enrolled onto the trial prior to its suspension continued treatment according to the study protocol, and as of 25 April death rates stood at six (0.8%) in Arm A, four (0.5%) in Arm B and eight (1.05%) in Arm C.

In order to gain further insights into the potential occurrence of cardiac events and sudden deaths, the study protocol will be amended to include a Cardiac Monitoring Plan (CMP). Patient recruitment will resume upon clearance by the relevant Independent Review Boards and Health Authorities.

"We welcome this recommendation from the DSMB," said Ed Holdener, head of global development at Roche. "Patient safety is of utmost importance to us and it is essential that safety data are carefully monitored, particularly in the adjuvant treatment setting."

Avastin was approved in February 2004 in the US and in January 2005 in the EU for the treatment of patients with previously untreated metastatic colorectal cancer. The first treatment to inhibit angiogenesis - the growth of a network of blood vessels that supply nutrients and oxygen to cancerous tissues - it targets the naturally occurring protein VEGF (Vascular Endothelial Growth Factor), a key mediator of angiogenesis, to cut off the blood supply that is essential for the growth of a tumour and prevent its spread throughout the body.

Following indications that its mechanism may be relevant in a number of malignant tumours, Roche is investigating its use in breast, lung, pancreatic cancer, ovarian cancer and renal cell carcinoma.