Phase I trial using a time-to-event continual reassessment strategy for dose escalation of @entity900 combined with XXXX and @entity1161 in @entity788 .

@entity1 @entity788 @entity137 @entity1161 @entity900 @entity262 @entity3 @entity136
PURPOSE: The primary objective of this study was to determine the maximum-tolerated dose of @entity900 that could be added to full-dose @entity136 and @entity1161 ( @entity1161 ) in @entity1 with @entity788 . @entity1 AND METHODS: Nineteen @entity1 were treated. @entity136 1,000 mg/m(2) was administered over 30 minutes on days 1, 8, and 15 of a 28-day cycle. @entity900 followed @entity136 on days 1 and 15. The initial dose level of @entity900 was 30 mg/m(2), escalated to a targeted dose of 50 mg/m(2) using Time-to-Event Continual Reassessment Method. @entity1161 was initiated on cycle 1, day 1, in 2.4 Gy fractions to a total dose of 36 Gy. A second cycle of chemotherapy was planned following a 1-week rest. RESULTS: Four of eight @entity1 experienced acute dose limiting @entity137 at the 50 mg/m(2) @entity900 dose level. @entity1 treated at 30 and 40 mg/m(2) @entity900 dose level tolerated therapy without dose-limiting @entity137 . Median survival was 10.7 months (95% CI, 5.4 to 18.2) for all @entity1 , and 12.9 months (95% CI, 7.4 to 21.2) for those without @entity3 . CONCLUSION: @entity900 at doses up to 40 mg/m(2) may be safely added to full-dose @entity136 and conformal @entity1161 . The Time-to-Event Continual Reassessment Method trial design allowed rapid completion of the study and confidence in the conclusion about the maximum tolerated dose, but accrued more @entity1 to a dose level above the maximum tolerated dose than the typical phase I design. Local and @entity262 control and survival in this study cohort supports further investigation of @entity136 -based @entity1161 and combination chemotherapy in this disease.
