A Feasibility Assessment and a Phase I/II Trial of MLN518 for Treatment of Patients With Recurrent Glioblastoma

Date de début de l'étude : 1 janvier 2007

Criteria: * Histologically confirmed glioblastoma: * Progressive or recurrent disease after prior radiotherapy (with or without chemotherapy) * Patients with a previous low-grade glioma that progressed after prior radiotherapy (with or without chemotherapy) and are found to have glioblastoma by biopsy are eligible * Measurable disease, defined as contrast-enhancing progressive or recurrent glioblastoma by MRI or CT imaging within the past 2 weeks * Must be maintained on a stable corticosteroid regimen from the time of baseline scan to the start of study treatment * Feasibility study only: * Planning to undergo surgical resection or biopsy * Stereotactic biopsy for confirmation of tumor progression or differentiation of tumor progression from treatment-induced effects allowed * Corticosteroids must be tapered to the lowest required steroid dose and patient must be maintained on a stable dose after surgery or biopsy * Karnofsky performance status 60-100% * Absolute neutrophil count \>= 1,500/mm\^3 * Hemoglobin \>= 10 mg/dL * Bilirubin =\< 1.5 mg/dL * AST and ALT =\< 4 times upper limit of normal * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier method contraception during and for 3 months after completion of study treatment * Mini Mental State Exam score \>= 15 * Mean QTc =\< 500 msec (with Bazett's correction) by screening electrocardiogram * LVEF \>= 40% * No history of familial long QT syndrome * No myocardial infarction within the past 6 months * No severe uncontrolled ventricular arrhythmias * No uncontrolled angina * No electrocardiographic evidence of acute ischemia or active conduction system abnormalities * No ongoing vomiting or nausea \>= grade 2 * No gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous alimentation * No active peptic ulcer disease * No other condition that would impair ability to swallow pills or absorb oral medications * No muscular dystrophy * No myasthenia gravis * No other known or suspected primary muscular or neuromuscular disease * No history of allergic reactions attributed to compounds of similar chemical or biologic composition to tandutinib (e.g., erlotinib hydrochloride, gefetinib, or doxazosin mesylate) * Patients who developed an acneiform/maculopustular rash while receiving either gefitinib or erlotinib hydrochloride are eligible unless the rash is considered an allergic reaction (angioedema/urticaria) or Stevens-Johnson syndrome * No ongoing or active infections * No psychiatric illness or social situations that would preclude study compliance * No other serious infection or medical illness * At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) * No other uncontrolled illness * No other malignancy within the past 5 years except for basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast * Recovered from prior therapy * At least 3 months since prior radiotherapy * No prior surgical procedures affecting absorption * No concurrent combination antiretroviral therapy for HIV-positive patients * No other concurrent investigational agents * No concurrent agent that would cause QTc prolongation * No concurrent prophylactic growth factors (e.g., filgrastim \[G-CSF\] or sargramostim \[GM-CSF\]) * At least 10 days since prior and no concurrent anticonvulsant drugs that induce hepatic metabolic enzymes (e.g., primidone, oxcarbazepine, phenytoin, carbamazepine, or phenobarbital) * No prior treatment with small molecule inhibitors of platelet-derived growth factor receptor (e.g., sunitinib malate, sorafenib, or imatinib mesylate) * Platelet count \>= 100,000/mm\^3 * No New York Heart Association class III or IV heart failure * Creatinine =\< 1.5 mg/dL OR creatinine clearance \>= 60mL/min