Vorinostat and Temsirolimus With or Without Radiation Therapy in Treating Younger Patients With Newly Diagnosed or Progressive Diffuse Intrinsic Pontine Glioma

Diffuse Intrinsic Pontine Glioma Clinical Trial

Official title: A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA, Vorinostat) With Temsirolimus in Children With Newly Diagnosed or Progressive Diffuse Intrinsic Pontine Glioma (DIPG)

Status Active, not recruiting

Clinical Trial Summary

This phase I trial studies the side effects and best dose of temsirolimus when given together with vorinostat and with or without radiation therapy in treating younger patients with newly diagnosed or progressive diffuse intrinsic pontine glioma, a tumor that arises from the middle portion of the brain stem. Vorinostat and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving temsirolimus and vorinostat with or without radiation therapy may be a better treatment for younger patients with diffuse intrinsic pontine glioma.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) or recommended phase 2 dose of temsirolimus in combination with vorinostat given every four weeks in patients with diffuse intrinsic pontine glioma (DIPG).

II. To define and describe the toxicities of the combination vorinostat and temsirolimus administered on this schedule.

SECONDARY OBJECTIVES:

I. To define the antitumor activity of the combination of vorinostat and temsirolimus within the confines of a phase 1 study.

II. To assess the biologic effects of vorinostat and temsirolimus on the signaling pathways of interest in these tumors.

III. To evaluate response with advanced neuroimaging (including magnetic resonance spectroscopy) and correlate with fiber tract changes using tractography and fractional anisotropy.

OUTLINE: This is a dose-escalation study of temsirolimus. Patients are assigned to 1 of 2 arms.

ARM I:

CHEMORADIOTHERAPY PHASE: Patients receive vorinostat once daily (QD) and undergo radiation therapy QD for 30 fractions over 6-7 weeks.

MAINTENANCE PHASE: Four to six weeks after the completion of radiation therapy, patients receive vorinostat PO QD and temsirolimus intravenously (IV) over 30-90 minutes on days 1-8 of each cycle. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive vorinostat PO QD and temsirolimus IV over 30-90 minutes on days 1-8 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months. ;

Related Conditions & MeSH terms

• Diffuse Intrinsic Pontine Glioma
• Glioma

• NCT number: NCT02420613
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: October 5, 2015
• Completion date: October 31, 2024