Study of Platelet Derived Growth Factor Receptor (PDGFR) in Recurrent Malignant Gliomas
The purpose of this study is to determine the survival, disease response, and side effects of Tasigna® (nilotinib) in patients who have malignant gliomas and are positive for Platelet Derived Growth Factor Receptor (PDGFR) amplification. This study is designed to test the hypothesis that patients with malignant gliomas with PDGFR amplification are sensitive to PDGFR kinase inhibitors.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of PDGFR Kinase Inhibitor in Biomarker-Enriched Recurrent Malignant Gliomas|
- To determine the efficacy of nilotinib in patients with recurrent malignant gliomas with PDGFR amplification as measured by 6-month progression-free survival. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- To define the safety of nilotinib in this population based on frequency of adverse events leading to study discontinuation and number of significant laboratory abnormalities. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
- To characterize the pharmacokinetics of nilotinib in this population by serum and cerebrospinal fluid (CSF) examination of drug and metabolites. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
|Study Start Date:||May 2010|
|Estimated Study Completion Date:||June 2016|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
400mg po (orally) BID (twice daily)
Other Name: Tasigna
Malignant gliomas (MG), including anaplastic gliomas (AG) and glioblastoma (GBM), are the most common primary brain tumor. Standard of care (surgery, radiotherapy, and temozolomide at initial diagnosis) results in a median survival of only 14 months. For patients with recurrent disease, conventional chemotherapy is generally ineffective with response rates <20%. Clearly there is need for improved treatments. Recent genome-wide studies have confirmed that GBM is a heterogeneous group of diseases that can be subclassified by shared genetic aberrations. The implication is that, in part, the underlying genetics may determine responsiveness to treatments and thus allow us to personalize therapy.
This is an, open-label, non-randomized, phase II study with oral nilotinib in adult patients with biomarker-enriched, recurrent malignant gliomas who have developed tumor progression after standard therapy. Patients will be treated with oral nilotinib (starting with the labeled dose of 400 mg) daily until disease progression or intolerance. One cycle is defined as 28 days.
Approximately 50 evaluable patients will be enrolled in this study, with 32 (grade IV) and 18 (grade III) in separate arms.
All patients will undergo clinical evaluation after each 28-day cycle. Neuroimaging studies (MRI) will be performed at baseline, 4 weeks, 8 weeks and then after every 2 cycles (8 weeks). If a contraindication for MRI's exists, patients will undergo contrast-enhanced CT scans. Laboratory tests will be obtained weekly during the first 4 weeks, and then on days 1 and 15 of all subsequent cycles. Patients will remain on study medication unless they develop tumor progression or unacceptable toxicity.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01140568
|Contact: Angel Nguyenfirstname.lastname@example.org|
|Contact: Joanne Brechlin||858-822-5352||Jbrechlin@ucsd.edu|
|United States, California|
|The Rebecca and John Moores UCSD Cancer Center||Recruiting|
|La Jolla, California, United States, 92093|
|Principal Investigator:||Santosh Kesari, MD, PhD||University of California Medical Center|