Phase 3 Trial Sample Clauses

Phase 3 Trial. Based on phase I/II results (above), Onconova has initiated a pivotal Phase 3 study with Rigosertib in previously untreated patients with metastatic pancreatic cancer. Patients are randomized in a 2:1 ratio to the combination of gemcitabine plus Rigosertib. vs. gemcitabine alone. The primary endpoint of this trial is overall survival. There will be a formal enrollment pause after 150 patients are entered in the trial. After 100 deaths have occurred in these patients, the DSMC will review overall safety and efficacy findings and make a recommendation for trial expansion (Q4, 2013). Assuming a positive recommendation, the DSMC will also perform a sample size re-estimation at this time. **. **. It is important to initiate a pivotal trial (vs. a stand-alone Phase 2 trial) while gemcitabine alone is still considered the standard of care (SOC) treatment for first-line pancreatic cancer. In addition, we desire a high level of assurance in a successful outcome and will be able to re-estimate our required sample size to achieve a statistically valid difference in overall survival between the two arms. The pancreatic cancer landscape is replete with compounds that have improved response rates and/or PFS in Phase 2 trials and subsequently failed in Phase 3. Response rates do not predict for survival in pancreatic cancer, and PFS is a difficult endpoint to accurately determine In addition, measuring progression is subject to the usual biases associated with open-label trials. Therefore, we have chosen to use the very “hard” endpoint of survival for the formal interim futility analysis of this randomized Phase 3 trial. ** **. ** **: **. **. **. Rigosertib CDP Addendum Confidential 1. PK-PD modeling analysis and responder analyses for dose justification 2. Target Product Profile per FDA guidance to use as gap identification and planning tool to ensure timely regulatory submission. 3. Additional regulatory and development risks and potential mitigation mechanisms. 4. Oral formulation: 1. Rigosertib IV for the treatment of higher risk MDS Relapsing or Progressing after Treatment with Azacitidine or Decitabine 2. Rigosertib IV combined with gemcitabine as first line treatment of metastatic pancreatic cancer 3. Rigosertib oral as first line therapy for transfusion dependent patients with lower risk MDS