A Phase II Study of Crenolanib (CP-868,596), a Selective and Potent Inhibitor of PDGFR, for the Treatment of Adult Gliomas
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.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
The primary end-point is overall response rate
Tumor response will be assessed by MRI scans every 2 months until disease progression
Elizabeth Maher, M.D., Ph.D.
University of Texas Southwestern Medical Center
United States: Food and Drug Administration
|Harold Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center||Dallas, Texas 75390|