Spots Global Cancer Trial Database for Erlotinib and Sirolimus in Treating Patients With Recurrent Malignant Glioma

Study Description

Brief Summary: RATIONALE: Erlotinib and sirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I/II trial is studying the side effects and best dose of erlotinib when given together with sirolimus and to see how well they work in treating patients with recurrent malignant glioma.

Detailed Description: OBJECTIVES: Primary * Determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of escalating doses of erlotinib hydrochloride in combination with sirolimus in adult patients with malignant glioma, who are not receiving enzyme-inducing anti-epileptic drugs (EIAED). (Phase I) * Evaluate preliminary efficacy (response rate \[RR\], progression-free survival \[PFS\], and overall survival \[OS\]) of erlotinib hydrochloride and sirolimus combination therapy in glioblastoma multiforme (GMB)/gliosarcoma (GS) patients who are not undergoing surgery at the time of recurrence or relapse (dose-expansion arm). (Phase II) * Evaluate molecular determinants of response to the combination of erlotinib hydrochloride and sirolimus, especially the roles of the mutation of EGFR (e.g., vIII mutant, other somatic mutations of vIII, and mutation/deletion of PTEN). Secondary * To characterize the safety and tolerability of erlotinib hydrochloride and sirolimus combination therapy in these patient populations. * To characterize the single-dose and repeated-dose pharmacokinetic (PK) profiles of erlotinib hydrochloride (in serum) and sirolimus (in whole blood) combination therapy in these patient populations. * To characterize, in pre- and/or post-treatment tumor samples, when available, expression levels of total and activated phosphorylated proteins relevant to the EGFR, VEGFR, and PI3K/mTOR signaling pathways, relevant downstream signaling network components, EGFR and VEGFR-related ligands, apoptosis (TUNEL), cell cycle control, and proliferation. * To assess pre- and/or post-treatment tumor samples, when available, for DNA-based changes (e.g., EGFR \[DNA\] amplification, EGFR and EGFRvIII mutations, and mutations/deletions in the PTEN gene) relevant to the molecular biology in GBM. OUTLINE: Patients receive oral erlotinib hydrochloride and sirolimus once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor tissue and blood sample collection periodically for pharmacological and biological studies. Samples are analyzed for concentrations of erlotinib hydrochloride and trough serum levels of sirolimus via HPLC, EGFR, EGFRvIII, PTEN and the phospho-specific antibodies associated with the MAPK and PI3K pathways via IHC, and EGFRvIII and sequencing of EGFR, PTEN and other critical genes via PCR, gene expression, and SNP analysis. Germline DNA will also be used to distinguish polymorphisms from somatic mutations in gene sequenced. After completion of study treatment, patients are followed periodically.

Keywords

Eligibility

Minimum Age: 18 Years

Eligible Ages: ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: No

Locations

Contact Details

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