Clinical Trial Detail

This phase I/II trial is studying carmustine and temozolomide when given together with radiation therapy, BCNU, O6-benzylguanine, and an autologous stem cell transplant in treating patients with newly diagnosed glioblastoma multiforme or gliosarcoma. Giving chemotherapy, such as temozolomide, carmustine, and O6-benzylguanine, and radiation therapy before a peripheral stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as filgrastim, and certain chemotherapy drugs, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy or radiation therapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy.

Genders Eligible for Study: Both

- Patients with glioblastoma multiforme or gliosarcoma

- The patient or legal guardian must be able to comprehend the informed consent form and sign prior to patient enrollment

- Patients must be consented for MGMT promoter methylation analysis of brain tumor tissue within twenty-eight days after surgery

- Karnofsky performance status at time of study entry must be >= 70%

- Life expectancy of >= 3 months

- Patients must agree to undergo repeat clinical neurological examinations and brain magnetic resonance imaging (MRI) with appropriate contrast after every other cycle of chemotherapy

- White blood cell (WBC) > 3000/uL

- Absolute neutrophil count (ANC) > 1500/uL

- Platelets > 100,000/uL

- Hemoglobin > 10 gm/100mL

- Total and direct bilirubin < 1.5 times upper limit of laboratory normal

- Serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), and alkaline phosphatase =< 3 times upper limit of laboratory normal

- Blood urea nitrogen (BUN) and serum creatinine < 1.5 times upper limit of laboratory normal

- Left ventricular ejection fraction (LVEF) >= 40%, however, subjects with an LVEF in the range of 40-49% should have cardiology clearance prior to intervention

- MGMT promoter methylation analysis of surgically resected tumor or tumor biopsy must demonstrate an unmethylated or hypomethylated MGMT promoter status

Other eligibility criteria may apply.

- Patients with active pulmonary infection and/or pulse oximetry < 90% and a corrected diffusion capacity of carbon monoxide (DLCO) < 70% of predicted

- Active systemic infection

- Patients who are human immunodeficiency virus (HIV) positive

- Pregnant or lactating women (a beta-human chorionic gonadotropin [HCG] level will be obtained from women of childbearing potential); fertile men and women should use effective contraception

- Previous chemotherapy for any malignancy including temozolomide, dacarbazine (DTIC) or prior nitrosourea

- Diabetes mellitus

- Bleeding disorder

- Methylated or hypermethylated MGMT promoter status within tumor tissue

- Medical or psychiatric condition which in the opinion of the protocol chairman would compromise the patient's ability to tolerate this protocol

- Prior interstitial radiotherapy, stereotactic or gamma knife surgery or implanted BCNU-wafers

Other exclusion criteria may apply.