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

Protocol # :
Recurrent Glioblastoma
Newly Diagnosed Glioblastoma
Disease Sites
Brain and Nervous System
Principal Investigator
Wen, Patrick, Yung
Site Investigator
Forst, Deborah
Site Research Nurses
Chau, Johny, E.
Gribbin, Nicola

Trial 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.

Eligibility Requirements

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

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

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®).