Recruitment Temporarily Suspended In An International Phase III Trial (AVANT) In Post-surgical Adjuvant Colon Cancer

J · medicine forum Guru Joined: 29 Apr 2005 Posts: 612

http://www.medicalnewstoday.com/medicalnews.php?newsid=38022
Recruitment Temporarily Suspended In An International Phase III Trial
(AVANT) In Post-surgical Adjuvant Colon Cancer

Article Date: 20 Feb 2006 - 12:00pm (PDT)

Roche announced that safety data from AVANT, a trial to study different
combination treatments for post-surgical adjuvant colon cancer, will be
further reviewed.

The review has been recommended by the AVANT independent Data Safety
Monitoring Board (DSMB) and is supported by Roche. The DSMB's
recommendation is based on two reasons: a safety concern observed in one
of the three study arms and the fast recruitment in the AVANT trial (more
than 200 patients per month) which could prevent adequate and timely
intervention. To enable the DSMB to undertake a review of 60-day safety
data the recruitment of additional patients will be temporarily halted.
Patients already enrolled into the AVANT trial will continue treatment as
per the study protocol. The safety data from these patients will continue
to be closely monitored by the DSMB. All ongoing Roche studies in the
oncology area will continue as planned.

Professor Aimery de Gramont, Principal Investigator for AVANT stated: “The
AVANT trial provides a unique opportunity to assess the effect of
combining an anti-angiogenic agent with standard chemotherapy in the
adjuvant colon cancer setting. The temporary halting of the recruitment is
necessary because in the adjuvant setting, the threshold for concern is
particularly low. However, we look forward to exciting findings that will
hopefully confirm the efficacy benefits that we have already observed in
the metastatic setting. This will open the avenue for new options for
patients suffering from colon cancer”

Since the AVANT trial began recruitment in December 2004, almost two third
of the target number of 3,450 patients have been enrolled and in January
2006 alone, more than 250 patients were recruited. The all cause mortality
excluding deaths due to the recurrent colon cancer in the AVANT trial for
FOLFOX-4 (Arm A) was 0.6% (4 cases), for FOLFOX-4 + Avastin (Arm B) 0.4%
(3 cases) and for XELOX + Avastin (Arm C) 1% (7 cases). These rates are
consistent with those reported in other adjuvant studies in colon cancer.
An occurrence of sudden deaths (4), especially in three younger patients
was noted in Arm C. Temporarily suspending recruitment will allow the DSMB
to perform a full safety assessment. The DSMB will continue to monitor all
adverse events in the study, including gastrointestinal perforations, a
side effect observed in previous studies of Avastin plus chemotherapy,
that has been observed in the AVANT study at a rate of 1%. This is less
than what has been observed in the metastatic setting (up to 2%).

“We concur with the DSMB's recommendation,” Ed Holdener, Head of Global
Development at Roche said. “Patient safety is of utmost importance to us.
Speed of recruitment in the AVANT trial is exceeding expectations and
safety should be carefully monitored, especially in the adjuvant setting
where the risk/benefit profile is different from that of the metastatic
setting. As such, we are committed to continuous monitoring and evaluation
of all safety data reported from the AVANT trial. Roche has an
unprecedented clinical trial programme in place in Oncology.”

A second study of Avastin plus chemotherapy as an adjuvant treatment for
early-stage colon cancer, called C-08, is continuing recruitment as
scheduled. Conducted primarily in the U.S by the National Surgical Breast
and Bowel Project (NSABP) in collaboration with the National Cancer
Institute (NCI), C-08 will enroll 2,714 patients. Patients are being
randomized into two arms:

* Arm 1: FOLFOX (control arm)
* Arm 2: FOLFOX+Avastin (experimental arm)

Like the AVANT study, the NSABP's C-08 trial has an independent DSMB that
reviews safety data on a regular basis. This study has enrolled more than
1,800 patients since the trial opened in 2004 and the DSMB has not made
any changes to the study protocol.

Avastin was approved in February 2004 in the USA and in the EU in January
2005 for the treatment of patients with previously untreated metastatic
colorectal cancer (mCRC) and has a well-established efficacy and safety
profile demonstrated through its use in over 54,000 patients worldwide.

There are currently more than 9,000 patients taking part in Avastin
clinical trials across several indications. At this time, the DSMB's
recommendation for AVANT does not affect ongoing and planned studies of
Avastin in colorectal cancer or in other tumour types.

J · medicine forum Guru Joined: 29 Apr 2005 Posts: 612

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