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GlioblastomaPhase 1/2NCT03782415

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

A Phase 1/2 study testing MN-166 and Temozolomide in people with Glioblastoma and Recurrent Glioblastoma, run by MediciNova at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioblastoma, Recurrent Glioblastoma, GBM
What is being tested?
MN-166 and Temozolomide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
64 participants
Where
1 siteUnited States
Study dates
29 Dec 2018to 7 Aug 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

None listed.

Who cannot join

  • 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;
  • 7) 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:
Show all 11Show fewer
  • 4 weeks or 5 half-lives (whichever is shorter) from any investigational agent;
  • 4 weeks from cytotoxic therapy (except 23 days for TMZ; 6 weeks from nitrosoureas);
  • 6 weeks from antibodies treatment (i.e., anti-VEGF antibody);
  • 4 weeks or 5 half-lives (whichever is shorter) from other anti-tumor therapies;
  • 2 days from NOVO-TTF (Optune®).

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: Phase 1b/2a 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

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.

Read the 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.

Being tested
MN-166, Temozolomide
Keywords
MN-166, GBM, glioblastoma, recurrent GBM, temozolomide, newly diagnosed glioblastoma
Medical subject headings
Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MN-166Drug

    Also called ibudilast

    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).

  • TemozolomideDrug

    Also called TMZ, Temodar, Temodal, Temcad

    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.

Study groups in NCT03782415
Study groupRoleWhat they receive
MN-166 and temozolomideExperimentalPart 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.
Receives: Drug: MN-166; Drug: Temozolomide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: 1-6 months

  2. Evaluate efficacy of ibudilast and TMZ combination treatment

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

    Measured: 1-6 months

Secondary outcomes (8)

  1. Evaluate Tmax

    Time from start of dosing at which the maximum concentration is observed)

    Measured: 1-6 months

  2. Cmax

    Maximum observed concentration)

    Measured: 1-6 months

  3. AUC

    Area under the concentration versus time curve from the start of dose administration to the last quantifiable point within the dosing interval.

    Measured: 1-6 months

  4. Terminal rate constant

    Calculated from the terminal slope of the log-linear regression of concentration with time.

    Measured: 1-6 months

  5. Terminal half-life

    Time required for the plasma concentration of a drug to decrease 50% in the final stage of its elimination

    Measured: 1-6 months

  6. Maximum tolerated dose determination

    Determine maximum tolerable dose of ibudilast taken in combination with TMZ

    Measured: 1-6 months

  7. Evaluate the safety of fixed-dose ibudilast in combination with TMZ

    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).

    Measured: 1-6 months

  8. Evaluate overall survival, response rate, and median 6-month progression-free survival (PFS6)

    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.

    Measured: 1-6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Dec 2018
  2. Study start29 Dec 2018
  3. Primary completion7 Aug 2023
  4. Study completion7 Aug 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
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.
Masking
None (open label)
Enrolment
64 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03782415
Sponsor's protocol ID
MN-166-GBM-1201
Status last verified
May 2025
First submitted
17 Dec 2018
Last updated
21 May 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 20534506

  • 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.

    PubMed 16674936

  • 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.

    PubMed 19925385

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing MN-166 and Temozolomide in people with Glioblastoma and Recurrent Glioblastoma, run by MediciNova at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 0 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Evaluate safety and tolerability of ibudilast and temozolomide combination treatment (time frame: 1-6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03782415, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2025.

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