Clinical Trials /

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

NCT03782415

Description:

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.

Related Conditions:
  • Astrocytoma
  • Gliosarcoma
  • Malignant Glioma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study to Evaluate Ibudilast and TMZ Combo Treatment in Newly Diagnosed and Recurrent Glioblastoma
  • 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 Newly Diagnosed or Recurrent Glioblastoma

Clinical Trial IDs

  • ORG STUDY ID: MN-166-GBM-1201
  • NCT ID: NCT03782415

Conditions

  • Glioblastoma
  • Recurrent Glioblastoma
  • GBM
  • Recurrent GBM

Interventions

DrugSynonymsArms
MN-166ibudilastMN-166 (ibudilast) and temozolomide
TemozolomideTMZ, Temodar, Temodal, TemcadMN-166 (ibudilast) and temozolomide

Purpose

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 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
      newly diagnosed or recurrent glioblastomas. To be eligible, subjects are histologically
      confirmed GBM (glioblastoma) or gliosarcoma, or astrocytomas with molecular features of GBM,
      WHO Grade 4. Recurrent GBM patients must have a Karnofsky Performance Status (KPS) ≥70 or
      Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Newly diagnosed
      glioblastoma GBM, gliosarcoma, or astrocytomas with molecular features of GBM 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 (ibudilast) when given in
      combination with TMZ, and determine the dose of MN-166 (ibudilast) 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 (ibudilast) 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 and up to 32 subjects are planned to be enrolled in Part
      2.
    

Trial Arms

NameTypeDescriptionInterventions
MN-166 (ibudilast) and temozolomideExperimentalPart 1: Combination treatment of MN-166 (ibudilast) 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 (ibudilast) and temozolomide combination treatment for 6 cycles until disease progression, unacceptable tolerability and/or toxicity or loss of life.
  • MN-166
  • Temozolomide

Eligibility Criteria

        Major Inclusion Criteria for Recurrent GBM Patients:

          1. Age 18 or older;

          2. Histologically confirmed GBM (glioblastoma), WHO Grade 4;

          3. Patients must have a Karnofsky Performance Status (KPS) ≥70 or Eastern Cooperative
             Oncology Group (ECOG) performance status of 0-2 (see Appendix 7);

          4. 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;

          5. Patients must be in first relapse;

               1. 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;

               2. Documented recurrence or progression by brain MRI imaging ≤14 days before study
                  registration;

               3. Measurable disease by RANO criteria (≥ 10 mm x 10 mm).

        Major Inclusion criteria for newly diagnosed patients:

          1. Ages 18 or older;

          2. Newly diagnosed glioblastoma or gliosarcoma (WHO Grade 4) confirmed by histology or
             astrocytomas with molecular features of gliobastoma;

          3. Starting maintenance therapy with temozolomide (150 mg/m^2 on Days 1-5 every 28 days)
             within 4 weeks prior to screening phase;

          4. 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;

          5. Karnofsky Performance Status ≥60 at time of screening;

          6. ECOG score of 0 or 1 at time of screening;

          7. Life expectancy of at least 3 months.

        Exclusion Criteria (applied to all patients):

          1. History of Grade 2 (CTCAE v4.0) or greater intracranial or intratumoral hemorrhage
             confirmed by either MRI or CT scan;

          2. Current use of anticoagulant treatment with coumadin (low-molecular-weight heparin and
             factor Xa inhibitors are permitted);

          3. Any systemic illness or unstable medical condition that might pose additional risk,
             including: cardiac, unstable metabolic or endocrine disturbances, renal or liver
             disease;

          4. Patients with a history of a different malignancy except the following circumstances:

               1. 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:

          1. 4 weeks or 5 half-lives (whichever is shorter) from any investigational agent;

          2. 4 weeks from cytotoxic therapy (except 23 days for TMZ; 6 weeks from nitrosoureas);

          3. 6 weeks from antibodies treatment (i.e., anti-VEGF antibody);

          4. 4 weeks or 5 half-lives (whichever is shorter) from other anti-tumor therapies;

          5. 2 days from NOVO-TTF (Optune®).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Evaluate safety and tolerability of ibudilast and temozolomide combination treatment
Time Frame:1-6 months
Safety Issue:
Description: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).

Secondary Outcome Measures

Measure:Evaluate Tmax
Time Frame:1-6 months
Safety Issue:
Description:Time from start of dosing at which the maximum concentration is observed)
Measure:Cmax
Time Frame:1-6 months
Safety Issue:
Description:Maximum observed concentration)
Measure:AUC
Time Frame:1-6 months
Safety Issue:
Description:Area under the concentration versus time curve from the start of dose administration to the last quantifiable point within the dosing interval.
Measure:Terminal rate constant
Time Frame:1-6 months
Safety Issue:
Description:Calculated from the terminal slope of the log-linear regression of concentration with time.
Measure:Terminal half-life
Time Frame:1-6 months
Safety Issue:
Description:Time required for the plasma concentration of a drug to decrease 50% in the final stage of its elimination
Measure:Maximum tolerated dose determination
Time Frame:1-6 months
Safety Issue:
Description:Determine maximum tolerable dose of ibudilast taken in combination with TMZ
Measure:Evaluate the safety of fixed-dose ibudilast in combination with TMZ
Time Frame:1-6 months
Safety Issue:
Description: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).
Measure:Evaluate overall survival, response rate, and median 6-month progression-free survival (PFS6)
Time Frame:1-6 months
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:MediciNova

Trial Keywords

  • ibudilast
  • MN-166
  • GBM
  • glioblastoma
  • recurrent GBM
  • temozolomide

Last Updated

May 22, 2020