A Phase I Open Label Safety Study to Evaluate the Pharmacokinetic Profile and Tolerance of Mibefradil Dose Finding in Subjects with Recurrent High-Grade Glioma Undergoing Standard, Repeated Temozolomide Treatment
This research is being done because this type of tumor is almost never cured with surgery, radiation, or chemotherapy. For this reason, we are trying to find new drugs to improve treatment for this tumor. The study you are being asked to join uses a drug called mibefradil. Mibefradil is a type of drug known as a calcium channel blocker. Mibefradil has previously been used to treat patients with high blood pressure. It was later found that mibefradilâ??s action on a particular type of calcium channel causes cancer cells to line up in a way that may increase the effect of temozolomide (TMZ), a drug that is used for the treatment of glioma. Mibefradil is considered experimental because it has not been approved by the U. S. Food and Drug Administration (FDA) for treatment of brain tumors.
1.Subjects must have histologically proven high-grade glioma. 2. Subjects must have measurable contrast-enhancing progressive or recurrent high-grade glioma 3. No prior cytotoxic therapies other than temozolomide and Gliadel wafers are allowed. 4.Subjects must have a Karnofsky performance status ï?³ 60% 5. Subjects must have the following organ and marrow function: Hemoglobin greater than 9 g/dL Absolute neutrophil count greater than 1,500/mcL Platelets greater than 100,000/mcL Total bilirubin less than 3 times institutional upper limit of normal AST(SGOT)/ALT(SGPT) less than 3 times institutional upper limit of normal Creatininewithin institutional upper limit of normal
This protocol is an open-label, non-randomized Phase I study that will evaluate the safety and pharmacokinetic profile of mibefradil tablets administered by mouth four times a day for one week immediately prior to the initiation of five days of temozolomide treatment at 150-200 mg/m2 per day. The last dose of mibefradil will be taken approximately 24 hours before the first dose of temozolomide. To accommodate pharmacokinetic sampling, the first day of Cycle 1 in the Dose-Finding portion must be a Monday ECG monitor should be worn continuously (24 hours/day) by the subject while taking mibefradil (Days 1-8) in Cycle 1
05/22/2013 04:02 AM