Study to Evaluate Ibudilast and TMZ Combo Treatment in Recurrent GBM
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|ClinicalTrials.gov Identifier: NCT03782415|
Recruitment Status : Recruiting
First Posted : December 20, 2018
Last Update Posted : February 5, 2019
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma Recurrent Glioblastoma GBM Recurrent GBM||Drug: MN-166 Drug: Temozolomide||Phase 1 Phase 2|
This is a multi-center open-label, dose escalation study to evaluate the safety, tolerability and efficacy of MN-166 (ibudilast) and Temozolomide combination treatment in patients with recurrent glioblastomas. To be eligible, subjects are histologically confirmed GBM (glioblastoma), WHO Grade IV, must have a Karnofsky Performance Status (KPS) ≥ 70 or Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
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 (ibudilast) when given in combination with TMZ, and determine the dose of MN-166 (ibudilast) to be used in Part 2 of the study. A total of 15-18 adult subjects are planned to be enrolled in Part 1.
Part 2 will evaluate the efficacy of MN-166 (ibudilast) and temozolomide combination treatment in patients with recurrent GBM as measured by the proportion of patients 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 and approximately 32 subjects are planned to be enrolled in Part 2.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Phase 1b/2a Multi-center, Open-label, Dose Escalation Study|
|Masking:||None (Open Label)|
|Official Title:||Phase 1b/2a Multi-center, Open-label, Dose Escalation Study to Evaluate the Safety, Tolerability and Efficacy of MN-166 (Ibudilast) and Temozolomide Combination Treatment in Patients With Recurrent Glioblastoma|
|Actual Study Start Date :||December 29, 2018|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||December 2020|
Experimental: MN-166 (ibudilast)
Part 1: Open-label, single arm, dose escalation of MN-166 (ibudilast) 60 mg/day and temozolomide (TMZ) 150 mg/m² combination treatment. Part 2: Open-label, fixed-dose MN-166 (ibudilast) and temozolomide (TMZ) combination treatment for 6 cycles until disease progression, unacceptable tolerability and/or toxicity or loss of life.
MN-166 (ibudilast) is an anti-inflammatory/neuroprotective agent. MN-166 (ibudilast) distributes well to the CNS (Sanftner et al. 2009) and it is a selective inhibitor of certain cyclic nucleotide phosphodiesterases (PDE) and the pro-inflammatory cytokine, macrophage migration inhibitory factor (MIF). At clinically-relevant plasma or CNS concentrations, MN-166 (ibudilast) selectively inhibits macrophage migration inhibitory factor (MIF) (Cho et al 2010) and, secondarily, PDE3, 4 and 10 (Gibson et al 2006).
Other Name: ibudilast
Part 1: Temozolomide (TMZ) (150 mg/m²) will be given orally once daily without food to all subjects on Days 1-5 during a 28-day cycle.
Part 2: If the TMZ-related toxicities are tolerated in Cycle 1, the dose of TMZ will be escalated to 200 mg/m² in combination with the fixed-dose MN-166 (ibudilast) for 6 cycles until disease progression, unacceptable tolerability and/or toxicity or loss of life.
Temozolomide is an oral chemotherapy drug. It is an alkylating agent used as a treatment of some brain cancers; and a first-line treatment for glioblastoma multiforme.
- Determine Progression-free survival pf patients at 6 months [ Time Frame: 6 months ]Determine proportion of patients (who take ibudilast & TMZ combination) who are progression-free at 6 months
- Safety Evaluation (Adverse events or discontinuation due to Dose limiting toxicities) [ Time Frame: 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)
- Maximum tolerated dose determination [ Time Frame: 6 months ]Determine maximum tolerable dose of ibudilast taken in combination with TMZ
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03782415
|Contact: Joanna Dojillo, MSc||8583731500 ext firstname.lastname@example.org|
|Contact: Kazuko Matsuda, MD, PhD, MPHemail@example.com|
|Principal Investigator:||Patrick Wen, MD||Dana-Farber Cancer Institute|