December 2008, May 2009
End-of-phase II meetings between AVEO Pharmaceuticals Inc. and FDA result in agreement concerning the design of the phase III trial of tivozanib for advanced renal cell carcinoma.
During the December 2008 meeting, the agency and AVEO discuss several study designs and FDA states that “a substantial, robust improvement in PFS that is clinically meaningful and statistically persuasive may be considered for regulatory decision.”
FDA also states that “a statistically significant improvement in OS is not required for regulatory approval, but a pre-specified OS analysis plan is still helpful in the regulatory decision making process.”
In the May 2009 meeting, the agency and AVEO discuss the final phase III protocol. Crossover design is not discussed and is not included in the phase III study itself (a later protocol added the crossover). See the FDA briefing documents for ODAC.