ZIOPHARM Oncology, Inc. (Nasdaq: ZIOP) today announced the initiation of the pivotal Phase III clinical trial for palifosfamide (ZymafosTM) in patients with front-line metastatic soft tissue sarcoma. The study, called PICASSO 3, is an international, randomized, double-blinded, placebo-controlled trial designed to enroll approximately 424 patients with metastatic soft tissue sarcoma who have never been treated with chemotherapy for metastatic disease. The study is designed to evaluate the safety and efficacy of palifosfamide administered with doxorubicin compared with doxorubicin administered with placebo, with no crossover between arms. Progression-free survival (PFS) is the primary endpoint for accelerated approval, with overall survival (OS) as the primary endpoint for full approval. Palifosfamide has Orphan Drug status in both Europe and the United States.
“Metastatic soft-tissue sarcoma is a disease for which we have seen few advances in treatment and no U.S. regulatory approvals in over two decades. Palifosfamide has demonstrated promising activity and tolerability in Phase II, including a clinically meaningful improvement in PFS.”
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.
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.
PICASSO 3 will be conducted at approximately 150 centers in North America, Europe, South America, Australia, Israel and Korea.
Vitamin K2 reduces the frequency, intensity, and duration of nighttime leg cramps