Safety Study of VAL-083 and Radiotherapy in Patients With Newly Diagnosed GBM Having Unmethylated MGMT Expression

Prior treatment

• Prior chemotherapy within the last 5 years.
• Prior radiation therapy of the head.
• Receiving concurrent investigational agents or has received an investigational agent within the past 30 days prior to the first dose of VAL-083.
• Prior systemic anti-angiogenic therapy.
• Placement of Gliadel® wafer at surgery.
• Concurrent illness, including severe infection, which may jeopardize the ability of the subject to receive the procedures outlined in this protocol with reasonable safety.
• Current alcohol dependence or drug abuse.

Other illness

• Planned surgery for other diseases (e.g. dental extraction).
• History of recent peptic ulcer disease (endoscopically proven gastric ulcer, duodenal ulcer, or esophageal ulcer) within 6 months of enrollment.
• History of coagulation disorder associated with bleeding or recurrent thrombotic events.
• Clinically manifest myocardial insufficiency (New York Heart Association \[NYHA\] III, IV) or history of myocardial infarction during the past 6 months; or uncontrolled arterial hypertension.
• Known hypersensitivity to the study treatment.
• Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Lab values

• Subject is pregnant (positive serum beta human chorionic gonadotropin \[b-HCG\] test at screening) or is currently breast-feeding, anticipates becoming pregnant/ impregnating their partner during the study or within 6 months after study participation, or subject does not agree to follow acceptable methods of birth control, such as hormonal contraception, intra-uterine pessar, condoms or sterilization, to avoid conception during the study and for at least 6 months after receiving the last dose of study treatment.

Age

• History of malignancy. Subjects with curatively treated cervical carcinoma in situ or basal cell carcinoma of the skin, or subjects who have been free of other malignancies for ≥5 years are eligible for this study.

Other

• Inability to undergo Gd-MRI.
• Legal incapacity or limited legal capacity.
• Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such.

• Newly diagnosed histologically proven supratentorial GBM
• Tumor tissue specimens from the GBM surgery or open biopsy must be available for MGMT gene promoter status analysis and central pathology review.
• Documented unmethylated MGMT gene promoter status
• Males or females ≥18\< 70 years of age.
• Interval of ≥2 weeks but ≤7 weeks after surgery or biopsy before first administration of study treatment.
• Cranial MRI must have been performed within 21 days of study entry and MRI must be used throughout the period of protocol treatment for tumor measurement. If the surgical procedure was a resection, cranial MRI performed within 72 hours of resection is preferred
• Stable or decreasing dose of steroids for ≥5 days prior to randomization.
• Karnofsky performance score ≥ 70%
• Patients must begin treatment with VAL-083 chemotherapy no sooner than 2 weeks and no later than 4 weeks from the diagnostic surgery.
• ANC ≥1,500/ µl
• Platelet count ≥ 100,000/µl
• Hemoglobin ≥ 10 gm/dl
• AST, ALT \< 2.5 times ULN
• Bilirubin \< 2.5 ULN
• Serum creatinine ≤ 1.5x ULN or creatinine clearance \> 50 mL/min (measured or calculated by the Cockcroft-Gault formula) (Cockcroft, 1976) at screening