This study is a Phase I study using vinblastine and sirolimus in patients with relapsed solid tumors including selected brain tumors and lymphoma. The investigators hypothesis is that the combination administration of weekly vinblastine and sirolimus is safe.
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advantage of the vinblastine-sirolimus regimen vs single agent in an orthopotic neuroblastoma mouse model and our unpublished data support a VBL in vitro pro-apoptotic plasma concentration of 1-2 nM range and an anti angiogenic concentration of 2pM.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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
14
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
Rady Children's Hospital-San Diego
San Diego, California, United States
SSM Cardinal Glennon Children's Medical Center
St Louis, Missouri, United States
Fletcher Allen Health Care
Burlington, Vermont, United States
The Hospital for Sick Children
Toronto, Ontario, Canada
Maximum tolerated dose of vinblastine in combination with sirolimus
Maximum tolerated dose (as defined by protocol) of vinblastine in combination with sirolimus
Time frame: 12 months
Safety data
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.
Time frame: 12 months
Response Rate
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.
Time frame: 12 months
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CHU Sainte-Justine
Montreal, Quebec, Canada