Efficacy, Safety and CNS Exposure of G-202 (Mipsagargin) in Patients With Recurrent or Progressive Glioblastoma

Inclusion Criteria:

- Written informed consent to participate in this study

- Histological or radiological confirmation of glioblastoma

- Recurrent or progressive GBM following at least one (1), but no more than two (2)
prior regimens; one of the prior regimens must have included surgery and/or
radiotherapy

- Age > 18 years

- Karnofsky Performance Status (KPS) ≥ 60%

- Life expectancy > 2 months

- Adequate hematologic, renal and hepatic function

- Adequate coagulation profile

- Not pregnant, nursing or planning to become pregnant; willing to use contraception

Exclusion Criteria:

- Deteriorating neurological symptoms, or need for increasing doses of corticosteroids
or new onset of seizures

- Surgical resection or major surgery within 4 weeks or stereotactic biopsy within 1
week of first G-202 treatment

- Toxicity from prior therapy (excluding alopecia) that has not resolved to ≤ Grade 1
unless otherwise specified

- Investigational or cytotoxic therapy within 28 days or nitrosoureas within 42 days of
the first treatment with G-202

- Currently requiring any type of full-dose anti-coagulation treatment, systemic
administration of antibiotics or chronic administration of anti-viral agents.

- History or evidence of cardiac risk, including QTc interval on screening ECG >470
msec, left ventricular ejection fraction (LVEF) < 50%, clinically significant
uncontrolled arrhythmias or arrhythmia requiring treatment with the exceptions of
atrial fibrillation and paroxysmal supraventricular tachycardia, history of acute
coronary syndromes within 6 months prior to the first dose of study therapy
(including myocardial infarction and unstable angina, coronary artery bypass graft,
angioplasty, or stenting)

- Uncontrolled cardiac or coronary artery disease

- Uncontrolled hypertension (mean systolic BP ≥ 160 mm Hg and/or mean diastolic BP ≥
100 mm Hg on 3 determinations 5 minutes apart while on 2 anti-hypertensive agents) or
hypertension requiring treatment with more than 2 anti-hypertensive agents

- Severe or uncontrolled medical disease, including uncontrolled diabetes, congestive
heart failure, chronic renal disease or chronic pulmonary disease

- Severe GI bleeding within 12 weeks of treatment with G-202

- Known history of HIV, hepatitis B or hepatitis C

- Documentation of keratosis follicularis (also known as Darier or Darier-White
disease)

- Requirement for chronic use of strong inhibitors or inducers of cytochrome (CYP3A4)
iso-enzymes

- Known hypersensitivity to any study drug component including thapsigargin
derivatives, polysorbate 20, or propylene glycol

- Any other condition, including concurrent medical condition, social circumstance or
drug dependency, which in the opinion of the investigator could compromise patient
safety and/or compliance with study requirements

- Another primary malignancy that has not been in remission for at least 2 years;
non-melanoma skin cancer, intraepithelial carcinoma of the cervix, or prostate cancer
with a current PSA ≤ 0.1 ng/mL is allowed