Background: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. Despite recent advances in the understanding of the molecular mechanism of tumorigenesis, the outcome remains poor. Atorvastatin is an inhibitor of HMG-CoA reductase, a rate-limiting enzyme in the mevalonate pathway. Preclinical studies have demonstrated pro-apoptotic, anti-proliferative, anti-invasive, and radiosensitizing properties of statins. To date, no prospective studies have addressed the anti-tumor effects of statins in GBM. This trial was designed to determine the efficacy and safety of atorvastatin in combination with radiotherapy and temozolomide (TMZ) in patients with newly diagnosed GBM. Methods: In this open-label, prospective, single-arm, phase II study, eligible patients will receive oral atorvastatin (40 mg/d for 3 weeks and 80 mg/d thereafter) until disease progression or significant toxicity, in combination with standard therapy comprising radiotherapy (60 Gy/30 fractions) and TMZ (75 mg/m²/d) in the 6-wk concurrent phase, then with TMZ (150-200 mg/m²/d on days 1-5 for 6 cycles). The key eligibility criteria includes: adults (≥18 years) with newly diagnosed GBM, who have undergone surgical resection or biopsy, ECOG performance status ≤ 2, adequate organ function, no prior chemotherapy or radiotherapy, stable dose of steroids for ≥14 days prior to registration, and written informed consent. The primary endpoint is progression free survival (PFS) at 6 months (RANO criteria). Secondary endpoints include overall survival (OS), and safety. A minimum of 80% power required at least 32 eligible patients to be enrolled starting January 2014 with a planned interim analysis after the first 15 evaluable patients. Statistical analysis plan includes Kaplan Meir techniques and Cox proportional hazard modeling. Clinical trial information: NCT02017717. .