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

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