Study to Evaluate Ibudilast and TMZ Combo Treatment in Newly Diagnosed and Recurrent Glioblastoma

NCT03782415 | Completed Phase 1 FDA Drug

• 1 other identifier: MN-166-GBM-1201
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

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.

Conditions

Glioblastoma; Recurrent Glioblastoma; GBM; Newly Diagnosed Glioblastoma

Keywords

MN-166; GBM; glioblastoma; recurrent GBM; temozolomide; newly diagnosed glioblastoma

Outcome Measures

Primary Outcomes (2)

• Evaluate safety and tolerability of ibudilast and temozolomide combination treatment

  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).

  1-6 months

• Evaluate efficacy of ibudilast and TMZ combination treatment

  Proportion of patients who are progression free at 6 months (PFS6) using the RANO criteria.

  1-6 months

Secondary Outcomes (8)

• Evaluate Tmax

  1-6 months

• Cmax

  1-6 months

• AUC

  1-6 months

• Terminal rate constant

  1-6 months

• Terminal half-life

  1-6 months

Study Arms (1)

MN-166 and temozolomide

EXPERIMENTAL

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.

Drug: MN-166; Drug: Temozolomide

Interventions

MN-166 DRUG

MN-166 is an anti-inflammatory/neuroprotective agent. MN-166 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 selectively inhibits macrophage migration inhibitory factor (MIF) (Cho et al 2010) and, secondarily, PDE3, 4 and 10 (Gibson et al 2006).

Also known as: ibudilast

MN-166 and temozolomide

Temozolomide DRUG

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.

Also known as: TMZ, Temodar, Temodal, Temcad

MN-166 and temozolomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 or older;
• Histologically confirmed GBM (glioblastoma), WHO Grade 4;
• Patients must have a Karnofsky Performance Status (KPS) ≥70 or Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (see Appendix 7);
• Previously received standard front-line GBM treatment including maximal surgical resection followed by external beam radiation therapy and TMZ therapy. Prior use of NovoTTF (Optune) and Gliadel wafers is allowed;
• Patients must be in first relapse;
• Relapse is defined as progression following initial therapy (i.e., radiation and/or chemotherapy). The intent therefore is that patients had no more than 1 prior therapy (i.e., initial treatment). If the patient had a surgical resection for relapsed disease and no anti-cancer therapy was instituted for up to 12 weeks, and the patient undergoes another surgical resection, this is considered to constitute one (1) relapse;
• Documented recurrence or progression by brain MRI imaging ≤14 days before study registration;
• Measurable disease by RANO criteria (≥ 10 mm x 10 mm).
• Ages 18 or older;
• Newly diagnosed glioblastoma or gliosarcoma (WHO Grade 4) confirmed by histology or astrocytomas with molecular features of gliobastoma;
• Starting maintenance therapy with temozolomide (150 mg/m\^2 on Days 1-5 every 28 days) within 4 weeks prior to screening phase;
• If patient is receiving corticosteroid, dose must be stable or decreasing for at least 5 days prior to the scan. If steroids are added or the steroid dose is increased between the date of the pretreatment MRI and the start of study, a new baseline MRI or CT scan is required;
• Karnofsky Performance Status ≥60 at time of screening;
• ECOG score of 0 or 1 at time of screening;
• Life expectancy of at least 3 months.

You may not qualify if:

• History of Grade 2 (CTCAE v4.0) or greater intracranial or intratumoral hemorrhage confirmed by either MRI or CT scan;
• Current use of anticoagulant treatment with coumadin (low-molecular-weight heparin and factor Xa inhibitors are permitted);
• Any systemic illness or unstable medical condition that might pose additional risk, including: cardiac, unstable metabolic or endocrine disturbances, renal or liver disease;
• Patients with a history of a different malignancy except the following circumstances:
• They have been disease-free for at least 2 years prior to starting study drug and are deemed by the investigator to be at low risk for recurrence of that malignancy. Patients with the following cancers are eligible if diagnosed and treated within the past 2 years: i. Cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin;
• \) Patients who have not recovered to ≤ Grade 1 toxicity by NCI CTCAE v4.0 from the toxic effects of previous therapy with exception of lymphopenia, alopecia and fatigue; 9) For use of other investigational drug or other anti-tumor treatment, the following time periods must have elapsed from the projected start of scheduled study treatment:
• weeks or 5 half-lives (whichever is shorter) from any investigational agent;
• weeks from cytotoxic therapy (except 23 days for TMZ; 6 weeks from nitrosoureas);
• weeks from antibodies treatment (i.e., anti-VEGF antibody);
• weeks or 5 half-lives (whichever is shorter) from other anti-tumor therapies;
• days from NOVO-TTF (Optune®).

Sponsors & Collaborators

• MediciNova: lead

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (3)

• Cho Y, Crichlow GV, Vermeire JJ, Leng L, Du X, Hodsdon ME, Bucala R, Cappello M, Gross M, Gaeta F, Johnson K, Lolis EJ. Allosteric inhibition of macrophage migration inhibitory factor revealed by ibudilast. Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11313-8. doi: 10.1073/pnas.1002716107. Epub 2010 Jun 8.

  PMID: 20534506 BACKGROUND

• Gibson LC, Hastings SF, McPhee I, Clayton RA, Darroch CE, Mackenzie A, Mackenzie FL, Nagasawa M, Stevens PA, Mackenzie SJ. The inhibitory profile of Ibudilast against the human phosphodiesterase enzyme family. Eur J Pharmacol. 2006 May 24;538(1-3):39-42. doi: 10.1016/j.ejphar.2006.02.053. Epub 2006 Mar 13.

  PMID: 16674936 BACKGROUND

• Sanftner LM, Gibbons JA, Gross MI, Suzuki BM, Gaeta FC, Johnson KW. Cross-species comparisons of the pharmacokinetics of ibudilast. Xenobiotica. 2009 Dec;39(12):964-77. doi: 10.3109/00498250903254340.

  PMID: 19925385 BACKGROUND

MeSH Terms

Conditions

Glioblastoma

Interventions

ibudilast; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Kazuko Matsuda, MD PhD MPH

  MediciNova, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1b/2a Single-center, Open-label, Dose-escalation study followed by a fixed-dose study to evaluate the safety, tolerability, and preliminary efficacy of MN-166 plus temozolomide in patients with newly diagnosed or recurrent glioblastoma.

Study Record Dates

• First Submitted: December 17, 2018
• First Posted: December 20, 2018
• Study Start: December 29, 2018
• Primary Completion: August 7, 2023
• Study Completion: August 7, 2023
• Last Updated: May 21, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)