Mibefradil Dihydrochloride and Temozolomide in Treating Patients With Recurrent Glioma
Condition: Brain and Central Nervous System Tumors
MeSH terms: Glioma; Nervous System Neoplasms; Central Nervous System Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Mibefradil dihydrochloride may stop the growth of tumor cells by blocking some of
      the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in
      different ways to stop the growth of tumor cells, either by killing the cells or by stopping
      them from dividing.

      PURPOSE: This phase I trial is studying the best dose of mibefradil dihydrochloride when
      given together with temozolomide in treating patients with glioma.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine the maximum-tolerated dose (MTD) of mibefradil dihydrochloride administered
           prior to five days of temozolomide (TMZ) at 150-200 mg/m² in subjects with progressive
           or recurrent high-grade glioma.

      Secondary

        -  Assess the safety of mibefradil dihydrochloride administered prior to five days of TMZ
           at 150-200 mg/m² when the mibefradil dihydrochloride dose is escalated from a starting
           dose of 100 mg/day, given four times a day for seven consecutive days.

        -  Determine the pharmacokinetic profile of mibefradil.

        -  Determine the steady state levels of mibefradil dihydrochloride on the last day of
           dosing.

        -  Assess the severity and frequency of adverse events for tested mibefradil
           dihydrochloride dose levels including cumulative toxicity and/or tolerance to adverse
           effects.

        -  Estimate the number and type of radiographic responses to treatment with mibefradil
           dihydrochloride and temozolomide.

        -  Assess the potential effect of mibefradil dihydrochloride on tumor metabolism as
           determined by Fluorothymidine Positron Emission Tomography (FLT PET) scans with the
           radiotracer [18F]-3'-fluoro-3'-deoxy-L-thymidine (dose-expansion cohort only).

      OUTLINE: This is a dose-escalation study of mibefradil dihydrochloride followed by a
      dose-expansion study.

      Patients receive mibefradil dihydrochloride orally (PO) 4 times a day on days 1-7 (days 1-8
      on first course) and temozolomide PO on days 8-12 (days 9-13 on first course). Treatment
      repeats every 28 days in the absence of disease progression or unacceptable toxicity.

      Blood samples are collected during the first course for pharmacokinetic studies.

      Patients in the dose-expansion cohort undergo [18F]-3'-fluoro-3'-deoxy-L-thymidine
      (FLT)-positron emission tomography (PET) at baseline and on day 7 of the first course of
      therapy.

      After completion of study therapy, patients are followed up every 2 months.
    

Intervention name(s): temozolomide; 3'-deoxy-3'-[18F]fluorothymidine; pharmacological study; Mibefradil
Intervention type(s): Drug; Other; Other; Drug
Intervention description(s): standard of care drug; tracer used for FLT PET CT
Intervention MeSH terms: Temozolomide; Mibefradil
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adult giant cell glioblastoma; adult glioblastoma; adult anaplastic astrocytoma; adult anaplastic ependymoma; adult anaplastic oligodendroglioma; adult mixed glioma; recurrent adult brain tumor