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Diffuse Intrinsic Pontine GliomaPhase 1NCT01393912

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

A Phase 1 study testing Crenolanib in people with Diffuse Intrinsic Pontine Glioma and Progressive or Refractory High-Grade Glioma, run by St. Jude Children's Research Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages 18 months to 21 years
What is being tested?
Crenolanib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
55 participants
Where
1 siteUnited States
Study dates
Jul 2011to Oct 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 months to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
Show all 27Show fewer
  • Age (years): < or equal to 5 and the maximum serum creatinine (mg/dL) is 0.8;
  • 5 < age < or equal to 10 and the maximum serum creatinine (mg/dL) is 1.0;
  • 10< 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.
  • Patients have had no previous treatment except corticosteroid use.
  • Patients must have radiologic evidence of recurrent, refractory or progressive high-grade glioma or DIPG. Patients must have either a diagnosis of HGG within the brain and/or spinal cord including DIPG or other high-grade glioma originating from the brainstem. A histologically confirmed diagnosis of anaplastic astrocytoma (WHO grade III), anaplastic oligodendroglioma (WHO grade III), anaplastic oligoastrocytoma (WHO grade III), anaplastic ganglioglioma (WHO grade III), pleomorphic xanthoastrocytoma with anaplastic features (WHO grade III), malignant glioneuronal tumor, glioblastoma multiforme (WHO grade IV) or gliosarcoma (WHO grade IV) is required. For patients with radiologic features of DIPG histologic confirmation of diagnosis is not required.
  • Patients must be able to swallow pills or take pills crushed in water based juice or puree (e.g. applesauce, apple juice) by mouth or gastric tube.
  • Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration.
  • Patients who are on dexamethasone must be on a stable or decreasing dose for at least one week prior to registration.
  • Patients must have fully recovered from the acute toxic effects of chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
  • Myelosuppressive chemotherapy: Patients must have received their last dose of known myelosuppressive anticancer chemotherapy at least four weeks prior to study registration or at least six weeks if nitrosourea. At least two weeks must have lapsed if patients received lower dose oral etoposide (50 mg/2) without experiencing evidence of myelosuppression (i.e. neutropenia or requiring transfusion with blood products)
  • Biologic agent: Patient must have recovered from any toxicity potentially related to the agent and received their last dose of the biologic agent ≥ 7 days prior to study registration. For biologic agents that have a prolonged half-life, the appropriate interval since last treatment should be discussed with the study chair prior to registration.
  • Monoclonal antibody treatment: At least three half-lives must have elapsed prior to registration. Such patients should be discussed with the study chair prior to registration.
  • Radiation: Patient has received radiation therapy prior to study registration Patients must have had their last fraction of local irradiation to the primary tumor ≥ 3 months prior to registration and their last fraction of craniospinal irradiation (>24Gy) > or equal to 3 months prior to registration. Patient has not received focal irradiation for symptomatic metastatic sites within 2 weeks prior to registration.
  • Bone Marrow Transplant: Patient must be ≥ 3 months since high dose chemotherapy and peripheral blood stem cell rescue prior to registration.
  • Growth factors: Patients must be off all colony forming growth factors(s) for at least 1 week prior to registration (filgrastim, sargramostim, erythropoietin) and at least 2 weeks for long-acting formulations (e.g. neupogen).

Who cannot join

  • 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).

Trial locations and contacts

1 site in 1 country.

United States1 site

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

Other trials in United States

About this study

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

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).

Read the detailed 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.

Being tested
Crenolanib
Keywords
crenolanib, radiation therapy, malignant brain tumors, pediatric
Medical subject headings
Diffuse Intrinsic Pontine Glioma, Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CrenolanibDrug

    Also called CP-868,596

    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

Study groups in NCT01393912
Study groupRoleWhat they receive
Stratum A PatientsOtherThe 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).
Receives: Drug: Crenolanib
Stratum B PatientsOtherThe 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).
Receives: Drug: Crenolanib

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    This is done using rolling 6 -design

    Measured: 2.5 years

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

    This is done using rolling 6 design

    Measured: 2.5years

  3. 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.

    Measured: 2.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jul 2011 (estimated)
  2. Study startJul 2011
  3. Primary completionSep 2014
  4. Study completionOct 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
55 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01393912
Sponsor's protocol ID
SJPDGF
Other IDs
V Fdn
Status last verified
Oct 2016
First submitted
11 Jul 2011
Last updated
26 Apr 2017
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Crenolanib in people with Diffuse Intrinsic Pontine Glioma and Progressive or Refractory High-Grade Glioma, run by St. Jude Children's Research Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Estimate the maximum tolerated dose (MTD) of crenolanib in pediatric research participants with newly diagnosed DIPG (time frame: 2.5 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01393912.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2017.

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