Thapsigargin Prodrug G-202 in Treating Patients with Recurrent or Progressive Glioblastoma

Inclusion Criteria

• Written informed consent to participate in this study
• Histological confirmation of glioblastoma
• Documentation of recurrent or progressive GBM following at least one (1) prior therapeutic regimen including upfront radiation and chemotherapy with temozolomide; up to three additional therapeutic regimens for disease progression prior to enrollment to the study is permitted
• Karnofsky performance status (KPS) >= 60%
• Life expectancy > 2 months
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
• Platelet count >= 100 x 10^9/L
• Hemoglobin >= 9.0 g/dL
• White blood cell (WBC) count >= 3.0 x 10^9/L
• Proteinuria level =< 2+
• Serum creatinine =< 1.5 x upper limit of normal (ULN) for the lab, calculated creatinine clearance >= 60 mL/min or 24-hour creatinine clearance >= 50 mL/min
• Albumin >= 2.8 g/dL
• Serum alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) and aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) levels =< 2.5 x ULN
• Alkaline phosphatase (ALP) =< 2.5 x ULN unless considered tumor-related
• Total bilirubin =< 1.5 x ULN for the lab
• Prothrombin time (PT) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN for the lab
• In women of child-bearing potential, negative serum pregnancy test within 14 days of the first infusion of G-202
• Women of child-bearing potential and male subjects with female partners of child-bearing potential must be willing to use acceptable methods of contraception to avoid pregnancy (for example, oral, injectable, or implantable hormonal contraceptive, tubal ligation, intra-uterine device, barrier contraceptive with spermicide, or vasectomized partner) beginning before the first infusion of G-202 and for 3 months after the last infusion of G-202

Exclusion Criteria

• Deteriorating neurological symptoms, or need for increasing doses of corticosteroids or new onset of seizures between the screening assessment and cycle 1 day 1
• Pregnancy or nursing
• 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 prior to the first treatment with G-202
• Investigation 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: * Corrected QT interval on screening electrocardiogram (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 blood pressure [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 gastrointestinal bleeding within 12 weeks of treatment with G-202
• Known history of human immunodeficiency virus (HIV), hepatitis B or hepatitis C
• Documentation of keratosis follicularis (also known as Darier or Darier-White disease)
• Requirement for chronic use of medications known to be strong inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) iso-enzymes; Note: if patients can stop receiving these medications, CYP3A4 inhibitors should be discontinued at least 7 days prior to starting treatment with G-202
• 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 prostate specific antigen (PSA) =< 0.1 ng/mL is allowed