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Also known as mibefradil, mibefradil dihydrochloride, Posicor, hypo fractionated radiation, intensity modulated radiation, IMRT
Mibefradil with Radiation · 2 trials · 2 indications
Determine the maximum tolerated dose (MTD) of mibefradil administered prior to five days of temozolomide (TMZ) at 150-200 mg/m2 in subjects with progressive or recurrent high grade glioma.
| Arm | Type | Description |
|---|---|---|
| Mibefradil with Radiation | EXPERIMENTAL | Patients will receive mibefradil dihydrochloride, which will be dose escalated from 150mg/day until the maximum tolerated dose (MTD) is determined, or until a dose of 350 mg/day is reached using a standard 3 + 3 design. Mibefradil dihydrochloride will be dosed orally in 4 divided doses per day for 17 consecutive days to the MTD. This will be given concurrently with hypofractionated radiation therapy. |
| Dose Finding and Dose Expansion | EXPERIMENTAL | DOSE FINDING 4 Levels For all Levels: Cycle 1 Mibefradil QID dosing, Days 1-8 (to accommodate PKs) (\*2 doses on Days 1 and 8) Temozolomide daily at 150-200 mg/m2, Days 9-13; Cycles 2+ Mibefradil QID, Days 1-7 Temozolomide daily at 150-200 mg/m2, Days 8-12 DOSE EXPANSION 28-day cycles FLT PET scans, Baseline x2, Day 7 Mibefradil MTD determined at Dose Finding QID, Days 1-7 Temozolomide daily at 150-200 mg/m2, Days 8-12 |
| Name | Type | Description |
|---|---|---|
| Mibefradil with Radiation | DRUG | Patients will receive mibefradil dihydrochloride, which will be dose escalated from 150mg/day until the maximum tolerated dose (MTD) is determined, or until a dose of 350 mg/day is reached using a standard 3 + 3 design. Mibefradil dihydrochloride will be dosed orally in 4 divided doses per day for 17 consecutive days to the MTD. This will be given concurrently with hypofractionated radiation therapy. |
| temozolomide | DRUG | standard of care drug |
| 3'-deoxy-3'-[18F]fluorothymidine | OTHER | tracer used for FLT PET CT |
| pharmacological study | OTHER | - |
| Mibefradil | DRUG | - |
Inclusion Criteria: * Sign written informed consent. * Histologically proven glioblastoma multiforme (GBM) that is progressive or recurrent following standard radiation therapy (RT) and temozolomide (i.e., at least "biopsy-proven" recurrent disease). Previous salvage therapies after first recurrenc...
Mibefradil with radiation is being studied in oncology for brain and central nervous system tumors, including glioblastoma multiforme (GBM). The approach combines the small molecule mibefradil with radiation therapy, and in one trial it was given with hypofractionated re-irradiation in patients with recurrent GBM.
Jazz Pharmaceuticals plc, which trades on Nasdaq under the ticker JAZZ, is the developer of mibefradil with radiation. The company is the sponsor associated with this oncology program, which pairs the small molecule mibefradil with radiation treatment for brain and central nervous system tumors.
Mibefradil with radiation is in Phase 1 clinical development. It is investigational and has not been approved for any indication. The program has one completed Phase 1 trial, and no trials are currently active.
Two completed Phase 1 trials have studied this approach. NCT02202993 tested mibefradil with hypofractionated re-irradiation therapy in recurrent GBM and enrolled 18 patients. NCT01480050 tested mibefradil dihydrochloride with temozolomide in patients with recurrent glioma and enrolled 28 patients. Both were conducted in the United States.
In recurrent GBM, mibefradil was studied with hypofractionated re-irradiation therapy in the completed Phase 1 trial NCT02202993, which enrolled 18 patients. That study was uncontrolled, non-randomized, and not double blinded, and it enrolled adults aged 18 years and older.