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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Arog Pharmaceuticals LLC
ClinicalTrials.gov Identifier:
NCT01229644
First received: October 26, 2010
Last updated: November 26, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Glioma
Drug: Crenolanib (CP-868,596)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Crenolanib (CP-868,596), a Selective and Potent Inhibitor of PDGFR, for the Treatment of Adult Gliomas

Resource links provided by NLM:


Further study details as provided by Arog Pharmaceuticals LLC:

Primary Outcome Measures:
  • The primary end-point is overall response rate [ Time Frame: Tumor response will be assessed by MRI scans every 2 months until disease progression ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The secondary end-point for this study is PFS [ Time Frame: 6-months and 12-months PFS will be measured ] [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: April 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Experimental: Cohort B
Adult patients with recurrent high grade glioma, including patients treated with bevacizumab.
Drug: Crenolanib (CP-868,596)
Highly potent inhibitor of both PDGFR receptors alpha and beta
Experimental: Cohort C
Adult patients with biopsy proven low grade glioma who have residual measurable disease.
Drug: Crenolanib (CP-868,596)
Highly potent inhibitor of both PDGFR receptors alpha and beta

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01229644

Locations
United States, Texas
Harold Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
Sponsors and Collaborators
Arog Pharmaceuticals LLC
Investigators
Principal Investigator: Elizabeth Maher, M.D., Ph.D. University of Texas Southwestern Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: Arog Pharmaceuticals LLC
ClinicalTrials.gov Identifier: NCT01229644     History of Changes
Other Study ID Numbers: ARO-BRE-001
Study First Received: October 26, 2010
Last Updated: November 26, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Arog Pharmaceuticals LLC:
Glioma
Brain Cancer
Recurrent glioma
Low grade glioma
PDGFR Inhibitor
Crenolanib (CP-868,596)
Neo-adjuvant Therapy

Additional relevant MeSH terms:
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Crenolanib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 30, 2014