Study of Crenolanib, a Selective and Potent Inhibitor of PDGFR, for the Treatment of Adult Gliomas

July 2, 2018 updated by: Arog Pharmaceuticals, Inc.

A Phase II Study of Crenolanib (CP-868,596), a Selective and Potent Inhibitor of PDGFR, for the Treatment of Adult Gliomas

The purpose of this study is to evaluate the antitumor efficacy of crenolanib (CP-868,596) in patients with recurrent high grade glioma and in patients with low grade glioma.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This Phase II study is designed to evaluate the antitumor efficacy of crenolanib (CP-868,596) in patients with recurrent high grade glioma and in patients with low grade glioma. Concurrently, the pharmacokinetics, tumor penetration and ability of crenolanib (CP-868,596) to inhibit PDGFR signaling will be evaluated when given as neo-adjuvant therapy to patients with radiographic evidence of malignant glioma prior to initial surgery.

The study will enroll 3 different cohorts of patients in parallel. Cohort A will enroll patients scheduled to undergo craniotomy and resection of newly diagnosed gliomas (both low and high grade). Patients in cohort A will be treated with crenolanib (CP-868,596) (300mg once daily, on an empty stomach) in the neo-adjuvant setting for a minimum of 3 days prior to surgical resection of their tumor mass. Twelve patients will be accrued on this neo-adjuvant cohort that will allow us to assess the ability of crenolanib (CP-868,596) to penetrate the tumor, not only in grade 3 and 4 gliomas (anaplastic astrocytomas and glioblastomas) that have a leaky BBB, but also in grade 2 gliomas (low grade gliomas) that tend to have a more intact blood-brain barrier (BBB).

Pharmacokinetic, pharmacodynamic and biological assessments will be conducted with tissue samples (plasma and brain tissue) obtained from these patients, when feasible.

Cohorts B and C will enroll patients with recurrent high grade gliomas or biopsy proven low grade glioma, respectively, who have residual measurable disease. Patients in cohorts B and C will be treated with crenolanib (CP-868,596) (300mg once daily on an empty stomach) continuously until they fulfill one of the criteria for study discontinuation. Magnetic resonance imaging (MRI) will be done to assess the tumor response as well as progression free survival (PFS). The primary endpoint for both cohorts B and C will be overall response rate according to the Response Evaluation Criteria In Solid Tumors (RECIST), as assessed by standard imaging modalities. In addition, 6-month Progression-free survival (cohort B) and 1-year PFS will also be assessed.

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Dallas, Texas, United States, 75390
        • Harold Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female, of any racial or ethnic group
  • Age 18 years or older
  • Patient able and willing to provide informed consent
  • Adequate kidney and liver function
  • Karnofsky Performance Status ≥ 70%
  • Negative serum pregnancy test or child bearing potential terminated by surgery, radiation, menopause or current use of two approved methods of birth control
  • Imaging suggestive of malignant glioma (Cohort A)
  • History of glioma with measurable disease by MRI (Cohorts B and C)
  • Histologically confirmed GBM with radiographic progression (Cohort B). These patients are permitted to have had prior therapy including surgery, radiation, Temozolomide, irinotecan and bevacizumab.
  • Histological confirmation of a low-grade glioma (Cohort C)

Exclusion Criteria:

  • Patient unable to provide informed consent (comatose or markedly cognitively impaired)
  • Female participants that are pregnant or breastfeeding
  • Any other concurrent anticancer therapy
  • Karnofsky Performance status < 70%
  • Any other concurrent investigational agents within 4 weeks of start of study drug
  • Patients with liver disease (known or active Hepatitis B or C; steatohepatitis; cirrhosis)

  • Hepatic:

    • Bilirubin greater than 1x the upper limit of normal
    • Transaminases greater than 1x the upper limit of normal

  • Abnormal renal function

    o Serum creatinine >1.7 ng/dl

  • Patients on concomitant medications that induce or inhibit CYP450, such as enzyme inducing anti-epileptic drugs (EIAEDs) (Appendix III) and troglitazone

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort A
Adult newly diagnosed glioma (both low and high grade) patients, who are able to to take Crenolanib (CP-868,596) for at least 3 days prior to surgical resection.
Drug: Crenolanib (CP-868,596)
Highly potent inhibitor of both PDGFR receptors alpha and beta
Other Names:
  • Crenolanib Besylate
Experimental: Cohort B
Adult patients with recurrent high grade glioma, including patients treated with bevacizumab. Patients are treated with Crenolanib (CP-868,596) continuously until they fulfill one of the criteria for study discontinuation.
Drug: Crenolanib (CP-868,596)
Highly potent inhibitor of both PDGFR receptors alpha and beta
Other Names:
  • Crenolanib Besylate
Experimental: Cohort C
Adult patients with biopsy proven low grade glioma who have residual measurable disease. Patients are treated with Crenolanib (CP-868,596) continuously until they fulfill one of the criteria for study discontinuation.
Drug: Crenolanib (CP-868,596)
Highly potent inhibitor of both PDGFR receptors alpha and beta
Other Names:
  • Crenolanib Besylate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The primary end-point is overall response rate
Time Frame: Tumor response will be assessed by MRI scans every 2 months until disease progression
Tumor response will be assessed by MRI scans every 2 months until disease progression

Secondary Outcome Measures

Outcome Measure
Time Frame
The secondary end-point for this study is PFS
Time Frame: 6-months and 12-months PFS will be measured
6-months and 12-months PFS will be measured

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Arog Pharmaceuticals, Inc.

Investigators

  • Principal Investigator: Elizabeth Maher, M.D., Ph.D., University of Texas Southwestern Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

  • Elizabeth A. Maher1, Clinton Stewart2, Kimmo Hatanpaa1, Jack Raisanen1, Tomoyuki Mashimo1, Xiao-Li Yang1, Chaitanya Muralidhara3, Christopher Madden1, Abhijit Ramachandran3, Bruce Mickey1, Robert Bachoo1, 1University of Texas Southwestern Medical Center, Dallas, TX, 2St. Jude's Children's Research Hospital, Memphis, TN, 3AROG Pharmaceuticals, LLC, Dallas, TX Neoadjuvant administration of the potent PDGFR inhibitor, crenolanib, to malignant gliomas at initial diagnosis: does it hit the target?

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2011

Primary Completion (Actual)

June 1, 2012

Study Completion (Actual)

December 1, 2012

Study Registration Dates

First Submitted

October 26, 2010

First Submitted That Met QC Criteria

October 27, 2010

First Posted (Estimate)

October 28, 2010

Study Record Updates

Last Update Posted (Actual)

July 5, 2018

Last Update Submitted That Met QC Criteria

July 2, 2018

Last Verified

July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ARO-BRE-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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