Erlotinib Hydrochloride and Isotretinoin in Treating Patients With Recurrent Malignant Glioma
Adult Anaplastic Astrocytoma
Adult Anaplastic Oligodendroglioma
Adult Diffuse Astrocytoma
Adult Giant Cell Glioblastoma
Adult Mixed Glioma
Recurrent Adult Brain Tumor
Drug: erlotinib hydrochloride
Other: laboratory biomarker analysis
Genetic: protein expression analysis
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Single Arm Open Label Study of Erlotinib and 13-cis-Retinoic Acid (CRA) in Patients With Recurrent Malignant Gliomas|
- Recommended phase II doses of erlotinib hydrochloride and isotretinoin [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]At least 3 patients will be treated at each dose level and the maximum tolerated dose (MTD) will be determined. Patients will be evaluated for dose-limiting toxicity (DLT) in the first 3 weeks on protocol.
- Toxicity as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
- Progression-free survival [ Time Frame: At 6 months ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: At 6 months ] [ Designated as safety issue: No ]
- Response rates (complete or partial response) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
- EGFRvIII, PTEN, cyclin D1, cyclin E, and RARbeta1 expression in tumor samples [ Time Frame: Pre-study ] [ Designated as safety issue: No ]
|Study Start Date:||May 2010|
|Study Completion Date:||March 2013|
|Primary Completion Date:||January 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (enzyme inhibitor, immunotherapy)
Patients receive isotretinoin PO QD on days 1-21 and erlotinib hydrochloride PO QD on days 1-28.
Drug: erlotinib hydrochloride
Other Names:Drug: isotretinoin
Other Names:Other: laboratory biomarker analysis
Correlative studyGenetic: protein expression analysis
I. To determine the recommended phase II doses of erlotinib (erlotinib hydrochloride) and 13-cis-retinoic acid (CRA) when administered to adults with recurrent malignant glioma who are not receiving cytochrome P450 enzyme-inducing antiepileptic drugs (EIAEDs).
I. To assess dose-related toxicities. II. To measure 6 month progression-free survival and overall survival. III. To estimate response rates in those patients with measurable disease. IV. To evaluate for epidermal growth factor receptor (EGFR)vIII, phosphatase and tensin homolog (PTEN), cyclin D1, cyclin E, and RARbeta1 expression in tumor samples from enrolled patients as predictors of clinical benefit from this combination.
OUTLINE: This is a dose-escalation study.
Patients receive isotretinoin orally (PO) once daily (QD) on days 1-21 and erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed for up to 2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01103375
|United States, North Carolina|
|Wake Forest University Health Sciences|
|Winston-Salem, North Carolina, United States, 27157|
|Principal Investigator:||Glenn Lesser||Wake Forest University Health Sciences|