NCT01204450

Temsirolimus and Valproic Acid in Treating Young Patients With Relapsed Neuroblastoma, Bone Sarcoma, or Soft Tissue Sarcoma

A Multi-center Phase I Trial of Temsirolimus in Combination With Valproic Acid in Children and Adolescents With Multiply Relapsed Pediatric Solid Tumors

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 7 (actual)
• Sponsor: UNC Lineberger Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 2 Years – 18 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Drugs such as temsirolimus and valproic acid may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Valproic acid may also stop the growth of solid tumors by blocking blood flow to the tumor. PURPOSE: This phase I trial is studying the side effects and the best dose of temsirolimus when given together with valproic acid in treating young patients with relapsed neuroblastoma, bone sarcoma, or soft tissue sarcoma.

Detailed description

OBJECTIVES: Primary * To identify the maximum-tolerated dose of temsirolimus in combination with valproic acid in highly pretreated pediatric patients with refractory solid tumors. Secondary * 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 disease response. * 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.

Conditions

• Brain and Central Nervous System Tumors
• Neuroblastoma
• Sarcoma
• Unspecified Childhood Solid Tumor, Protocol Specific

Interventions

Type	Name	Description
DRUG	Temsirolimus	60-230mg/m2 weekly during each 28 day course, for up to 12 courses
DRUG	Valproic Acid	All patients will be given oral VPA (5 mg/kg, 3 times a day for each 28 day course, up to 12 courses

Timeline

• Start date: 2009-11-01
• Primary completion: 2012-11-01
• Completion: 2013-03-01
• First posted: 2010-09-17
• Last updated: 2016-12-23

Locations

2 sites across 1 country: United States