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

NCT01393912 | Completed Phase 1

• 2 other identifiers: SJPDGFV Fdn
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

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

Keywords

crenolanib; radiation therapy; malignant brain tumors; pediatric

Outcome Measures

Primary Outcomes (3)

• Estimate the maximum tolerated dose (MTD) of crenolanib in pediatric research participants with newly diagnosed DIPG

  This is done using rolling 6 -design

  2.5 years

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

  This is done using rolling 6 design

  2.5years

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

  Individual pharmacokinetic parameters will be estimated using nonlinear mixed effects modeling methods (NONMEM) to estimate both the inter- and intra-subject variability.

  2.5 years

Study Arms (2)

Stratum A Patients

OTHER

The patients are newly diagnosed Diffuse Intrinsic Pontine Glioma patients. Patients may take crenolanib as an intact tablet or crushed in apple sauce/juice. Currently accruing to dose level 3 (170 mg/m\^2).

Drug: Crenolanib

Stratum B Patients

OTHER

The patients are recurrent, refractory or progressive high-grade glioma including Diffuse Intrinsic Pontine Glioma patients. Patients may take crenolanib as an intact tablet or crushed in apple sauce/juice. Currently accruing to dose level 4 (220 mg/m\^2).

Drug: Crenolanib

Interventions

Crenolanib DRUG

Crenolanib orally administered as whole or crushed tablets once per day with concurrent Radiation Therapy. Crenolanib will continue at the same dose level post Radiation Therapy

Also known as: CP-868,596

Stratum A Patients; Stratum B Patients

Eligibility Criteria

• Age: 18 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age must be ≥ 18 months and \< or equal to 21 years
• Body surface Area (BSA) ≥ 0.55 m\^2
• Lansky (for research participants ≤ 16 years) or Karnofsky (for research participants \> 16 years) performance score ≥ 40 at the time of study enrollment
• Adequate organ function at the time of study enrollment as follows:
• Bone marrow: Absolute neutrophil count (ANC) ≥ 1,000/μL, platelet count ≥ 75,000/μL (transfusion independent), hemoglobin concentration ≥ 8g/dL (may be transfused)
• Renal: Normal serum creatinine concentration based on age as shown below or glomerular filtration rate (GFR) \> 70 ml/min/1.73m\^2
• Age (years): \< or equal to 5 and the maximum serum creatinine (mg/dL) is 0.8;
• \< age \< or equal to 10 and the maximum serum creatinine (mg/dL) is 1.0;
• \< age \< or equal to 15 and the maximum serum creatinine (mg/dL) is 1.2;
• \>15 and the maximum serum creatinine (mg/dL) is 1.5;
• Hepatic: Total bilirubin concentration \< or equal to 1.5 times the institutional upper limit of normal for age; SGPT \< or equal to 3 times the institutional upper limit of normal
• Pancreatic: Serum amylase \< or equal to 3 times the institutional upper limit of normal for age; lipase \< or equal to 3 times the institutional upper limit of normal
• Female research participants of childbearing age must not be pregnant as confirmed by a serum or urine pregnancy test within 1 week of start of treatment. Participants must not be breast-feeding.
• Males or females of reproductive potential may not participate unless they have agreed to use two effective contraceptive methods. Abstinence in a non-sexually active child will be sufficient birth control.
• Diagnosis of DIPG or high-grade glioma originating from the brainstem.

You may not qualify if:

• Metastatic disease outside the CNS.
• Use of enzyme-inducing anticonvulsants (EIACs) within 7 days prior to registration.
• Research participants with uncontrolled infection
• Research participants with any concomitant significant medical illness that in the investigator's opinion cannot be adequately controlled with appropriate therapy, or that would impair the evaluation of side effects related to this treatment, alter drug metabolism or the tolerance to this treatment
• Research participants receiving any other anticancer or investigational drug therapy
• Prior therapy with crenolanib
• Of note, the use of any concomitant medication that may affect CYP3A function except for dexamethasone, should be discussed with the principal investigator of this study (or her designee).

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• Arog Pharmaceuticals, Inc.: collaborator
• The V Foundation for Cancer Research: collaborator

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Diffuse Intrinsic Pontine Glioma; Glioma

Interventions

crenolanib

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Alberto Broniscer, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2011
• First Posted: July 13, 2011
• Study Start: July 1, 2011
• Primary Completion: September 1, 2014
• Study Completion: October 1, 2016
• Last Updated: April 26, 2017

Record last verified: 2016-10

Locations

US (1)