Genentech and Roche suspend enrollment in Phase III adjuvant treatment trial (AVANT)

Genentech, the manufacturers of Avastin, announced on February 12, 2005 that they were temporarily suspending enrollment in a large, international trial of Avastin™ (bevacizumab) and chemotherapy for early-stage colon cancer to give safety monitors an opportunity to review information about an unusually high number of deaths of patients in one arm of the trial.

In addition, enrollment to the trial has been unexpectedly high — over 200 patients a month — and data safety monitors need more time to ensure that trial treatment is safe.

The AVANT trial compares three regimens for treating stage III and high-risk stage II colon cancer after surgery to remove the tumor in the colon.

• ARM A:  FOLFOX (oxaliplatin, leucovorin, and continuous infusion 5FU) alone
• ARM B:  FOLFOX plus Avastin™ (bevacizumab)
• ARM C:  XELOX (oxaliplatin and oral capecitabine) plus Avastin™

Since the study opened in December of 2004, there have been an usually high number of participant deaths in Arm C — the XELOX plus Avastin arm.  Excluding deaths from recurrent colon cancer, there have been

• 4 deaths (0.6%) in Arm A
• 3 deaths(0.4%) in Arm B
• 7 deaths (1%) in Arm C

Accrual to the trial has been rapid, with over two-thirds of the targeted 3,450 participants enrolled by January 2006.  The trial is being conducted internationally, including in the United States, in 308 centers in 33 countries.  Patients who have already been enrolled in the trial will continue treatment.

Gastrointestinal perforation rates in the trial have been about 1%, lower than those in previous trials with Avastin™ for people with metastatic colorectal cancer.

Roche, the manufacturers of Eloxatin™ (oxaliplatin), also released information about the trial suspension.

Another Phase III trial for stage II and III patients that compares FOLFOX alone to FOLFOX plus Avastin™ will continue accrual.  NSABP C-08 is a two-arm trial that does not include a capecitabine regimen.  The National Surgical Adjuvant Breast and Bowel Project (NSABP), a cooperative group conducting the trial, has consulted with their own Data Safety Monitoring Board.  The DSMB has found no discrepancies in either deaths or gastrointestinal perforation in the C-08 trial participants.