A Phase I Study of Vinblastine and Sirolimus in Pediatric Patients With Recurrent or Refractory Solid Tumors Including CNS Tumors
Published data demonstrating a survival advantage of the vinblastine-sirolimus regimen vs
single agent in an orthopotic neuroblastoma mouse model and our unpublished data support a
VBL in vitro pro-apoptotic plasma concentration of 1-2 nM range and an anti angiogenic
concentration of 2pM. These plasma concentrations are achievable with a 6 mg/m2 (apoptosis)
and 1 mg/m2 VBL regimen (anti-angiogenesis) weekly regimen. We expect that vinblastine
delivered at any given dose, as described in the protocol, will carry both anti-apoptotic
and antiangiogenic activity. Safety and preliminary efficacy of both drugs in pediatric
tumors support the development of a clinical trial.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of vinblastine in combination with sirolimus
Dose will be escalated every 3 to 6 patients using the 3+3 standard design regimen. Enrollment of the next cohort will occur after the previous cohort has completed a full cycle without any dose limiting toxicity (DLT). If a DLT is observed in 1 out of 3 patients during the first cycle, 3 additional patients will be enrolled to receive the same dose. If a DLT is observed in another patient, 3 additional patients will be enrolled to receive a dose level below this dose. The MTD will be defined as the dose level below which DLTs are seen in ≥ 2 of at least 6 patients dosed.
12 months
Yes
Sylvain Baruchel, MD
Principal Investigator
The Hospital for Sick Children, Toronto Canada
Canada: Health Canada
1000016324
NCT01135563
April 2010
April 2012
Name | Location |
---|---|
Fletcher Allen Health Care | Burlington, Vermont 05401 |
Rady Children's Hospital-San Diego | San Diego, California 92123 |
SSM Cardinal Glennon Children's Medical Center | St. Louis, Missouri 63104 |