Study to Evaluate Ibudilast and TMZ Combo Treatment in Newly Diagnosed and Recurrent Glioblastoma
- Conditions
- Newly Diagnosed GlioblastomaRecurrent GlioblastomaGBMGlioblastoma
- Interventions
- Registration Number
- NCT03782415
- Lead Sponsor
- MediciNova
- Brief Summary
Part 1 is an open-label, single-arm, dose escalation study of MN-166 (ibudilast) and temozolomide (TMZ) combination treatment. Evaluate safety and tolerability of ibudilast (MN-166) and TMZ combination treatment for 1 cycle (28 days); determine dosage in dose-finding study. Part 2 will evaluate efficacy of fixed-dose MN-166 (ibudilast) and TMZ combination treatment for 6 cycles (\~6 months) until disease progression, unacceptable tolerability and/or toxicity or loss of life.
- Detailed Description
This is a single-center open-label, dose-escalation study to evaluate the safety, tolerability and efficacy of MN-166 (ibudilast) and Temozolomide combination treatment in patients with newly diagnosed or recurrent glioblastoma. To be eligible, subjects are histologically confirmed glioblastoma or gliosarcoma, or astrocytomas with molecular features of glioblastoma, WHO Grade 4. Recurrent glioblastoma patients must have a Karnofsky Performance Status (KPS) ≥70 or Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Patients having newly diagnosed glioblastoma, gliosarcoma, or astrocytomas with molecular features of glioblastoma must have a KPS ≥60 and ECOG score 0-1. This is divided into a dose-escalation phase (Part 1) followed by a fixed-dose phase (Part 2).
Part 1 will evaluate the safety and tolerability of MN-166 when given in combination with temozolomide, and determine the dose of MN-166 to be used in Part 2 of the study. Up to 18 adult subjects are planned to be enrolled in Part 1.
Part 2 will evaluate the efficacy of MN-166 and temozolomide combination treatment as measured by the proportion of subjects who are progression-free at 6 months. Other outcome measures include the evaluation of overall survival, response rate, and median six-month progression-free survival up to 2 years and up to 50 subjects are planned to be enrolled in Part 2.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 64
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description MN-166 and temozolomide MN-166 Part 1: Combination treatment of MN-166 60 mg/day (30 mg twice a day) for 28 days and temozolomide 150 mg/m² on Days 1-5 of 28-day cycle. Part 2: Open-label, fixed-dose MN-166 and temozolomide combination treatment for 6 cycles until disease progression, unacceptable tolerability and/or toxicity or loss of life. MN-166 and temozolomide Temozolomide Part 1: Combination treatment of MN-166 60 mg/day (30 mg twice a day) for 28 days and temozolomide 150 mg/m² on Days 1-5 of 28-day cycle. Part 2: Open-label, fixed-dose MN-166 and temozolomide combination treatment for 6 cycles until disease progression, unacceptable tolerability and/or toxicity or loss of life.
- Primary Outcome Measures
Name Time Method Evaluate safety and tolerability of ibudilast and temozolomide combination treatment 1-6 months Determine the proportion of patients with
* Treatment-emergent adverse events (TEAEs) as measured by the CTCAE v4.0 and
* Treatment discontinuations due to TEAEs and Dose-Limiting Toxicities (DLTs).Evaluate efficacy of ibudilast and TMZ combination treatment 1-6 months Proportion of patients who are progression free at 6 months (PFS6) using the RANO criteria.
- Secondary Outcome Measures
Name Time Method Evaluate overall survival, response rate, and median 6-month progression-free survival (PFS6) 1-6 months Overall survival will be measured for each subject with time origin at the date of Study Day 1 until recorded date or death or last follow-up visit.
Cmax 1-6 months Maximum observed concentration)
AUC 1-6 months Area under the concentration versus time curve from the start of dose administration to the last quantifiable point within the dosing interval.
Terminal rate constant 1-6 months Calculated from the terminal slope of the log-linear regression of concentration with time.
Terminal half-life 1-6 months Time required for the plasma concentration of a drug to decrease 50% in the final stage of its elimination
Evaluate the safety of fixed-dose ibudilast in combination with TMZ 1-6 months Reporting of treatment-emergent adverse events
* Treatment-emergent adverse events (TEAEs) as measured by the CTCAE v4.0 and
* Treatment discontinuations due to TEAEs and Dose-Limiting Toxicities (DLTs).Evaluate Tmax 1-6 months Time from start of dosing at which the maximum concentration is observed)
Maximum tolerated dose determination 1-6 months Determine maximum tolerable dose of ibudilast taken in combination with TMZ
Trial Locations
- Locations (1)
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States