A Multi-center Phase I Trial of Temsirolimus in Combination With Valproic Acid in Children and Adolescents With Multiply Relapsed Pediatric Solid Tumors
- To identify the maximum-tolerated dose of temsirolimus in combination with valproic
acid in highly pretreated pediatric patients with refractory solid tumors.
- To estimate the objective response rate in patients treated with this regimen.
- To estimate the progression-free survival of patients treated with this regimen.
- To explore the association between tumor IGF-IR, mTOR expression, HDAC, autophagy
biomarkers, and sera levels of temsirolimus, valproate, and VEGF-A with toxicity and
- To evaluate the ability of selected member divisions of a newly developed North
Carolina-based pediatric oncology consortium to cooperate in clinical trials.
OUTLINE: This a multicenter, dose-escalation study of temsirolimus.
Patients receive temsirolimus IV over 30-60 minutes on days 1, 8, 15, and 22 and oral
valproic acid* 3 times daily on days 1-28. Treatment repeats every 28 days for up to 12
courses in the absence of disease progression or unacceptable toxicity.
Blood samples are collected at baseline and periodically during study for pharmacokinetic
and VEGF-A studies. Tumor tissue samples from archived biopsy are also analyzed for IGF-IR,
mTOR expression, HDAC, and autophagy biomarkers.
After completion of study therapy, patients are followed every 3 months for 1 year, every 4
months for 2 years, and then every 6 months for 2 years.
NOTE: * Doses of valproic acid are titrated beginning 3-7 days prior to starting
temsirolimus to achieve plasma levels of 75-100 µg/mL.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (MTD) of temsirolimus in combination with valproic acid
The planned starting dose of Temsirolimus is 60mg/M2. The traditional 3+3 design will be used, where the MTD is defined as the dose with the probability of a DLT of 0.20
Julie Blatt, MD
UNC Lineberger Comprehensive Cancer Center
United States: Food and Drug Administration
|Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill||Chapel Hill, North Carolina 27599-7570|
|Carolina Healthcare System||Charlotte, North Carolina|