PDGFR Inhibitor Crenolanib in Children/Young Adults With Diffuse Intrinsic Pontine Glioma or Recurrent High-Grade Glioma

Diffuse Intrinsic Pontine Glioma Clinical Trial

Official title: Platelet Derived Growth Factor Receptor (PDGFR) Inhibitor Crenolanib in Children and Young Adults With Newly Diagnosed Diffuse Intrinsic Pontine Glioma or Recurrent High-Grade Glioma Including Diffuse Intrinsic Pontine Glioma

Status Completed

Clinical Trial Summary

This is a Phase I clinical trial evaluating crenolanib (CP-868,596), an inhibitor of Platelet Derived Growth Factor Receptor (PDGFR)-kinase in children and young adults with newly diagnosed diffuse intrinsic pontine glioma (DIPG) (Stratum A) or in recurrent, progressive or refractory High Grade Glioma (HGG) including DIPG (Stratum B). This study drug targets the most commonly amplified region of genome found in DIPG and pediatric high grade glioma (HGG) which encodes for the PDGF receptor kinase. An oral investigational agent crenolanib will be administered daily during and after local radiation therapy (RT) in Diffuse Intrinsic Pontine Glioma DIPG (Stratum A), or daily for children with recurrent/refractory HGG (Stratum B).

Clinical Trial Description

Primary Objectives:

• To estimate the maximum tolerated dose (MTD) of crenolanib administered concurrently with RT in pediatric research participants with DIPG

• To estimate the MTD of crenolanib in children and young adults with recurrent/refractory HGG including DIPG

• To characterize the pharmacokinetics of crenolanib in pediatric patients and relate drug disposition to toxicity

Exploratory Secondary Objectives:

• To characterize toxicities and/or adverse events associated with the chronic use of crenolanib

• To evaluate the association between specific polymorphisms of drug metabolizing enzymes and the pharmacokinetics of crenolanib

• To evaluate changes in phosphorylation of targets of PDGF pathway activation in peripheral blood mononuclear cells and investigate the possible relationship between these changes, plasma drug levels of crenolanib and outcome measures

• To evaluate PDGFR, genotype, protein expression and DNA amplification in tumor tissue where available

• To investigate whether magnetic resonance imaging (MRI) techniques that reflect tumor pathophysiology (metabolism, oxygenation, perfusion and vessel wall integrity) are correlated with clinical response

• To characterize the neural tract involvement and tumor progression routes of pediatric brainstem glioma based upon anatomical magnetic resonance imaging and diffusion tensor imaging

• To assess the pattern of failure in radiation therapy in Stratum A participants.

• To describe the research participants' and parents' perspective of symptoms and the quality of life of children enrolled on this phase I trial

• To describe the quality of life and the impact of self-care activities of parents of pediatric research participants enrolled on this phase I trial

• To assess the impact of therapeutic alliance and social support on peace of mind, hope, anxiety/depression and quality of life among parents of pediatric research participants enrolled on this phase I trial

Stratum A- Appropriate dose RT will be administered in 30-33 fractions over approximately 6 weeks for Stratum A patients. Treatment with crenolanib will start on the same day as RT and continue daily during and after Radiation Therapy for a maximum treatment duration of 2 years. We plan to treat a maximum of 5 cohorts of research participants (dosage levels 0, 1, 2, 3, and 4) with escalating doses of crenolanib. A cycle is defined as 28 days and the first 8 weeks of therapy will constitute the dose-limiting toxicity (DLT)-evaluation period.

Stratum B - Crenolanib will be administered orally on a daily basis continuously for 28 days, which defines one cycle. The maximum treatment duration will be 2 years. We plan to treat a maximum of 5 cohorts of research participants (dosage levels 0, 1, 2, 3, and 4) with escalating doses of crenolanib. Dose escalation will be independent of Stratum A escalation. The DLT evaluation period will be four weeks. ;

Related Conditions & MeSH terms

• Diffuse Intrinsic Pontine Glioma
• Glioma
• Progressive or Refractory High-Grade Glioma

• NCT number: NCT01393912
• Study type: Interventional
• Source: St. Jude Children's Research Hospital
• Status: Completed
• Phase: Phase 1
• Start date: July 2011
• Completion date: October 2016