MGMT-Methylated Glioblastoma Clinical Trial
Official title:
Randomized Pilot Study of Six Months Adjuvant Temozolomide (TMZ) vs No Adjuvant TMZ in Patients With Newly Diagnosed MGMT Methylated Glioblastoma (GBM) Following Standard Concurrent Radiation and TMZ
The primary objective of this trial is to evaluate overall survival of patients with O[6]-methylguanine-DNA methyltransferase (MGMT) methylated glioblastoma treated with or without six months of adjuvant TMZ after standard radiation (6000 centigray (cGy)) plus concurrent Temozolomide (TMZ). Secondary Objectives include to prospectively assess the overall adverse event profile in the two treatment arms. To compare lymphocyte counts overtime between the two treatment arms and to prospectively compare quality of life in the two treatment arms as assessed by MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) and Neurological quality of Life/minimal infecting dose (NeuroQoL) (MID). The study will also compare progression-free survival between the two treatment arms.
Recent phase III trials in patients with newly diagnosed patients with glioblastoma have demonstrated that adding new agents (such as cilengitide, bevacizumab, or nivolumab) to standard radiation and TMZ do not improve survival in this disease. The modest effects on survival observed with the Optune® device are offset by the high costs, inconvenience, and impact on the social interactions of patients wearing this device. Unfortunately, there are currently no novel therapies poised to displace the European Organization Research & Treatment Cancer (EORTC) regimen as the standard of care for patients with newly diagnosed Glioblastoma Multiforme (GBM).As a result, a formal evaluation of the efficacy of the 6 months of adjuvant TMZ in this regimen is important to patients and research studies. This is of particular importance in the 40% of patients who have MGMT methylated glioblastoma. The very small benefit observed in MGMT unmethylated patients has led investigators in Europe and the United States of America (including Cancer Therapy Evaluation Program (CTEP) sponsored studies) to approve clinical trials in MGMT unmethylated patients with newly diagnosed glioblastoma that entirely omit TMZ in both the concurrent and the adjuvant settings Given the marginal value of TMZ in the MGMT unmethylated patient population, the investigator's propose to study the value of adjuvant TMZ in the subset of the MGMT methylated population. If omitting adjuvant TMZ is not detrimental to outcomes in the methylated population then it is extremely unlikely to benefit the unmethylated population where TMZ has even less effect. Therefore, exploring the value of the six months of adjuvant TMZ in patients with newly diagnosed MGMT methylated glioblastoma is important. If this was shown to be of minimal value in prolonging survival there would be an immediate impact on both the standard care of patients and research efforts to improve therapeutic outcomes. ;