Study of Vinblastine and Sirolimus in Pediatric Patients With Recurrent or Refractory Solid Tumors Including Central Nervous System Tumors
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|ClinicalTrials.gov Identifier: NCT01135563|
Recruitment Status : Completed
First Posted : June 2, 2010
Last Update Posted : December 3, 2013
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumors Central Nervous System Tumors||Drug: Vinblastine and Sirolimus||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Vinblastine and Sirolimus in Pediatric Patients With Recurrent or Refractory Solid Tumors Including CNS Tumors|
|Study Start Date :||April 2010|
|Primary Completion Date :||April 2012|
|Study Completion Date :||April 2012|
Experimental: Vinblastine and Sirolimus
The standard 3+3 Phase 1 trial design will be used for the conduct of this study. Three to six patients can be concurrently enrolled onto a dose level. Accrual is suspended when a cohort of three has been enrolled until toxicity data for that cohort have been reported, or when the study endpoints have been met.
Drug: Vinblastine and Sirolimus
Patients will be enrolled to receive vinblastine and sirolimus in 28 day cycles. Using the 3+3 standard Phase1 design, vinblastine will be administered via IV push on Days 1, 8, 15, 22. The starting dose of 4 mg/m2 (Dose Level 1) is 67% of the established MTD (6 mg/m2) for this schedule in pediatrics. Dose escalation will take place in a standard 3+3 design, in which doses will increase by approximately 20 to 25% in successive 3-patient cohorts.
Sirolimus (rapamycin) will be given by mouth (tablet or suspension) once daily throughout the cycle. Ideally patients will remain on the same dose form (tablet or suspension) for the duration of the study. All patients will be assigned a target sirolimus serum trough
- Maximum tolerated dose of vinblastine in combination with sirolimus [ Time Frame: 12 months ]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.
- Safety data [ Time Frame: 12 months ]Safety data will be described for all patients receiving at least one dose of vinblastine and sirolimus. Safety data will include values for hematology, serum chemistry, vital signs, and adverse events. The proportion of patients experiencing adverse events, serious adverse events, dose limiting toxicities and treatment delays will be summarized for each dosing cohort.
- Response Rate [ Time Frame: 12 months ]The proportion of patients experiencing progressive disease, stable disease, partial responses or complete responses will be summarized in tabular format. Progression free survival and duration of any responses will also be summarized.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01135563
|United States, California|
|Rady Children's Hospital-San Diego|
|San Diego, California, United States, 92123|
|United States, Missouri|
|SSM Cardinal Glennon Children's Medical Center|
|St. Louis, Missouri, United States, 63104|
|United States, Vermont|
|Fletcher Allen Health Care|
|Burlington, Vermont, United States, 05401|
|The Hospital for Sick Children|
|Toronto, Ontario, Canada, M5G 1X8|
|Montreal, Quebec, Canada, H3T 1C5|
|Principal Investigator:||Sylvain Baruchel, MD||The Hospital for Sick Children, Toronto Canada|