NDA 21-063

4/13/00

Click here to start

Table of Contents

Regulatory standard for first line therapy of colorectal cancer is to improve overall survivalOncologic Drugs Advisory Committee Recommendation contained inFDA Guidance on Requirements for Approval of New Drugs for Treatment of Colon and Rectal Cancers

5-FU plus leucovorin has been the standard of care and will prolong survival compared to 5-FU monotherapy

Lack of correlation between progression free survival and overall survival in 7 published controlled studies

Regulatory History

The sponsor submitted information on 33 clinical studies, and provided datasets for 8 studies of which 2 were randomized controlled studies comparing 5-FU/LV to 5-FU/LV plus oxaliplatin in first line treatment of patients with colorectal cancer

Study 2962-Enrolled patients August 1995 - July 1997

Study 2962 Amended Analysis Plan

Adverse Event Differences in Study 2961

Adverse Event Differences in Study 2962

Neurotoxicity in Study 2962

Cumulative Neurotoxicity in Study 2962

randomized controlled multicenter studies

Weaknesses of Application

“Moreover, a single favorable study among several similar attempts that failed to support a finding of effectiveness would not constitute persuasive support for a product use” FDA Guidance on Providing Clinical Evidence of Effectiveness, 1998

“Although an unexplained failure to substantiate the results of a favorable study in a second controlled trial is not proof that the favorable study was in error — studies of effective agents can fail to show efficacy for a variety of reasons — it is often reason not to rely on the single favorable study.”FDA Guidance on Providing Clinical Evidence of Effectiveness, 1998

Criteria for submitting a single study

FDA Review Team

Author: Steven Hirschfeld