This phase I trial is studying the side effects and best dose of erlotinib hydrochloride when given with isotretinoin in treating patients with recurrent malignant glioma. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Isotretinoin may help cells that are involved in the body's immune response to work better. Giving erlotinib hydrochloride together with isotretinoin may kill more tumor cells
PRIMARY OBJECTIVES: 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). SECONDARY OBJECTIVES: 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
5
Given PO
Given PO
Correlative study
Correlative study
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
Recommended phase II doses of erlotinib hydrochloride and isotretinoin
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.
Time frame: 3 weeks
Toxicity as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0
Time frame: Up to 2 years
Progression-free survival
Time frame: At 6 months
Overall survival
Time frame: At 6 months
Response rates (complete or partial response)
Time frame: Up to 2 years
EGFRvIII, PTEN, cyclin D1, cyclin E, and RARbeta1 expression in tumor samples
Time frame: Pre-study
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