Roche, Genentech: Recruitment to resume in Avastin phase 3 trial in early stage colon cancer

By E. Janene Geiss

Philadelphia, May 23 - Genentech announced Tuesday a decision by Roche, following a recommendation from an independent Data Safety Monitoring Board, to resume patient recruitment into Avant, an international phase 3 study of Avastin (bevacizumab), Xelox and Folfox chemotherapy regimens in early stage colon cancer.

Patient recruitment will resume upon clearance by the relevant Independent Review Boards and European Health Authorities, according to a company news release.

The board based its recommendation to resume enrollment on a detailed analysis of safety data from the trial, officials said.

The halt in enrollment was implemented to conduct a 60-day safety review for recently recruited patients and assess occurrences of cardiac and unknown deaths in one of the treatment arms.

Company officials said the board concluded that the current safety profile and overall mortality observed in the trial are consistent with those seen in other early stage colon cancer trials.

Currently, there is no indication of an imbalance of cardiac events between the treatment arms of the Avant study.

However, to gain further insight on the overall occurrence of cardiac events and sudden deaths, the Avant study protocol will be amended to include a cardiac monitoring plan that will involve an enhanced baseline cardiac assessment and additional basic cardiac investigations, officials said.

"Following rapid patient enrollment into the Avant study, we believe the temporary halt of recruitment to assess safety was the right thing to do for patients," Hal Barron, Genentech's senior vice president of development and chief medical officer, said in the release.

The U.S.-based adjuvant trial, Nsabp C-08, has continued to enroll as planned with no changes to its protocol, officials said.

The company said that the Avant and Nsabp C-08 trials, which have different treatment arms, provide an opportunity to investigate whether adding Avastin to standard chemotherapy as adjuvant therapy may be safe and effective in patients with early stage colon cancer.

Avant is a study being conducted by Roche to evaluate whether the addition of Avastin to chemotherapy as an adjuvant treatment following surgery can reduce the chance of recurrence in patients with stage 2 and 3 colorectal cancer. The study will randomize 3,450 patients into three regimens. Since the Avant trial was begun in December 2004, about two-thirds of the target number of 3,450 patients has been enrolled.

Patients who had already enrolled into the Avant trial prior to the recruitment suspension continued treatment according to the study protocol, officials said.

The data review undertaken by the monitoring board, with a cut-off date of April 25, revealed that mortality from all causes in the Avant trial, excluding deaths due to recurrent colon cancer, was 0.8%, or six cases, for Folfox-4 (Arm A), was 0.5%, or four cases, for Folfox-4 plus Avastin (Arm B), and was 1.05%, or eight cases, for Xelox plus Avastin (Arm C).

These rates are consistent with those reported in other adjuvant studies in colon cancer, officials said.

Broad use of Avastin eyed

Genentech said it is pursuing a broad development program for Avastin that includes more than 130 clinical trials across 25 different types of cancer. Avastin is being evaluated in phase 3 clinical trials for its potential use in adjuvant and metastatic colorectal, renal cell (kidney), breast, pancreatic, non-small cell lung, prostate and ovarian cancers.

In April, Genentech submitted a supplemental Biologics License Application to the FDA for Avastin in combination with platinum-based chemotherapy for first-line treatment of advanced, non-small cell lung cancer other than predominant squamous histology.

The company said it also plans to submit a sBLA for Avastin for the treatment of metastatic breast cancer in the second quarter of 2006. Avastin also is being evaluated in earlier-stage trials as an investigational agent in a variety of solid tumor cancers and hematologic malignancies.

Genentech is a South San Francisco, Calif., biotechnology company.

Roche, which owns the majority interests in Genentech, is a Basel, Switzerland, pharmaceutical company.

© 2015 Prospect News.
All content on this website is protected by copyright law in the U.S. and elsewhere. For the use of the person downloading only.
Redistribution and copying are prohibited by law without written permission in advance from Prospect News.
Redistribution or copying includes e-mailing, printing multiple copies or any other form of reproduction.