A Non-randomized, Open-label Dose-finding Trial of Combined Cytotoxic and Immune-Stimulatory Strategy for the Treatment of Resectable Primary Malignant Glioma

Fecha de inicio: 1 de abril de 2014

Inclusion Criteria: Newly diagnosed supratentorial brain lesion compatible with a high grade glioma by MR (magnetic resonance) with no prior treatment with either gene therapy, chemotherapy or radiation treatments that is amenable to attempted gross total resection (GTR).Intraoperative histological frozen section at the time of tumor resection should be compatible with high-grade glioma. If intraoperative diagnosis is not high grade glioma, the patient will not be enrolled. "High grade glioma" can include:Glioblastoma multiforme (WHO grade IV); Anaplastic astrocytoma (WHO grade III); Anaplastic oligodendroglioma (WHO grade III); and Anaplastic ependymoma (WHO grade III). Karnofsky score ≥70 (Karnofsky scoring system used to quantify general well-being and activities of daily life; scores range from 0 to 100 where 100 represents perfect health and 0 represents death) CBC (complete blood count)/differential obtained within 14 days prior, with adequate bone marrow function defined as follows: Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3; Platelets ≥ 100,000 cells/mm3; Hemoglobin ≥ 10.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥10.0 g/dl is acceptable.); Adequate renal function, as defined below: BUN (blood urea nitrogen) ≤ 30 mg/dl within 14 days prior. Creatinine ≤ 1.7 mg/dl within 14 days prior. Adequate hepatic function, as defined below: Bilirubin ≤ 2.0 mg/dl within 14 days prior. ALT (alanine aminotransferase)/AST (aspartate aminotransferase) ≤ 3x laboratory upper limit of normal within 14 days prior. Male and female; both genders must use contraception if of reproductive capacity Capable of informed consent 18-75 years of age For women of child bearing age, a negative pregnancy test performed within 14 days of surgery Exclusion Criteria: Diffusely multifocal lesion that is not amenable to GTR (gross total resection) Tumors infiltrating the cerebellum, bilateral corpus callosum ("butterfly glioma"), ventricular system, or brain stem Infratentorial high grade glioma Primary central nervous system (CNS) disease that would interfere with subject evaluation Current diagnosis of other cancer except curative cervical cancer in situ, basal or squamous cell carcinoma of the skin. Evidence of other significant disease including hematologic, renal or liver disease that is not explained by the patient's current medical condition or concomitant disease, (i.e. levels of absolute neutrophil count (ANC), hemoglobin, platelets, clotting time, serum creatinine, etc). Final decision on inclusion will be made by physician, concerning suitability of patient for surgery. HIV, Hepatitis B, Hepatitis Active systemic infection Immunosuppressive disorders (chronic steroid therapy, acquired or congenital immune deficiency syndromes, autoimmune disease) Serious medical conditions (CHF (congestive heart failure), angina, diabetes mellitus, Chronic obstructive pulmonary disease, abnormal bleeding diathesis) Any contraindication for undergoing MRI (magnetic resonance imaging) Pregnant or lactating females Unacceptable anesthesia risk Evidence of bleeding diathesis or use of anticoagulant medication or any medication that may increase the risk of bleeding that cannot be stopped prior to surgery. Prior gene therapy Allergy to valacyclovir or unable to take oral tablets