A Phase II Study of Crenolanib (CP-868,596), a Selective and Potent Inhibitor of PDGFR, for the Treatment of Adult Gliomas
18 Years
N/A
Both
Glioma
Trial Information
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
The primary end-point is overall response rate
Outcome Time Frame:
Tumor response will be assessed by MRI scans every 2 months until disease progression
Safety Issue:
No
Principal Investigator
Elizabeth Maher, M.D., Ph.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Texas Southwestern Medical Center
Authority:
United States: Food and Drug Administration
Study ID:
ARO-BRE-001
NCT ID:
NCT01229644
Start Date:
April 2011
Completion Date:
December 2014
Related Keywords:
- Glioma
- Glioma
- Brain Cancer
- Recurrent glioma
- Low grade glioma
- PDGFR Inhibitor
- Crenolanib (CP-868,596)
- Neo-adjuvant Therapy
- Glioma
Name | Location |
|---|---|
| Harold Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center | Dallas, Texas 75390 |
