The pivotal trial protocol was developed in a process with the U.S. Food and Drug Administration (FDA) that included discussion at an End of Phase II meeting and a subsequent dialogue for Special Protocol Assessment (SPA). FDA advised that PFS could be used as a primary endpoint outside of formal SPA with the study outcome subject to review. Regulatory acceptability will depend on the magnitude of the difference between the trial study arms as well as a risk and benefit analysis. Having reached consensus with FDA, including on the methodology of radiologic evaluation of PFS, and based upon external expert opinion, the Company elected to initiate the pivotal Phase III trial without formal SPA and retaining PFS as a primary endpoint.
Soft Tissue Sarcomas (American Cancer Society Atlas of Clinical Oncology)
The PICASSO 3 trial has 85% power to detect a 0.60 hazard ratio (HR) advantage for the palifosfamide combination arm for PFS. Following a pre-determined number of PFS events and Independent Data Monitoring Committee (IDMC) review and recommendation, coupled with review of the then available survival data by the IDMC (to which the Company and Investigators will remain blinded), the Company could file for accelerated approval based on PFS. The Company and its external advisors estimate that a median increase in PFS of 3 months or greater over the control arm (control arm median PFS estimated to be 4.3 months) could achieve a targeted hazard ratio (HR=0.60; p=0.0005, one-tailed) and also predict a demonstrable improvement in overall survival. Sarcoma and oncology experts consulted by the Company believe that this would represent a clinically meaningful improvement in PFS in this disease setting and that this study design is a statistically reliable evaluation regarding whether the experimental intervention is safe and provides clinically meaningful benefit. The PICASSO 3 study is designed as a close follow-on study to the publicly-reported PICASSO trial, which demonstrated a statistically significant improvement in PFS (HR=0.39; median PFS improvement of 3.4 months, p=0.023) for the combination over doxorubicin alone.
PICASSO 3 will be conducted at approximately 150 centers in North America, Europe, South America, Australia, Israel and Korea.
About Soft Tissue Sarcoma
Soft tissue sarcomas are cancers of the body soft tissues, including cartilage, muscle, fat, nerves, blood vessels and other connective tissue. They may develop in any part of the body, but are most common in the trunk, arms, and legs.
According to the American Cancer Society, 10,520 new cases of adult soft tissue sarcomas will be diagnosed in the United States in 2010. No new therapies have been approved for use in sarcoma in the U.S. in over 20 years.
Source: ZIOPHARM Oncology, Inc.
