Clinical Review Abstract
Trials in Progress Abstract
Abstracts selected for publication but not presentation at the Annual Meeting
Abstracts granted an exception in accordance with ASCO's Conflict of Interest Policy
RTOG 0913: A phase I study of daily everolimus (RAD001) in combination with radiation therapy and temozolomide in patients with newly diagnosed glioblastoma.
Central Nervous System Tumors
2013 ASCO Annual Meeting
J Clin Oncol 31, 2013 (suppl; abstr 2047)
Author(s): Prakash Chinnaiyan, Minhee Won, Patrick Y. Wen, Amyn Rojiani, Merideth M Wendland, Thomas A. DiPetrillo, Benjamin W. Corn, Minesh P. Mehta; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; Radiation Therapy Oncology Group, Philadelphia, PA; Dana-Farber Cancer Institute, Boston, MA; Georgia Health Sciences University, Augusta, GA; Willamette Valley Cancer Institute, Eugene, OR; Department of Radiation Oncology, Rhode Island Hospital, Providence, RI; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; University of Maryland, Baltimore, MD
Background: To determine the safety of the mTOR inhibitor everolimus (RAD001) administered daily with concurrent radiation and temozolomide in newly diagnosed glioblastoma patients. Methods: Everolimus was administered daily with concurrent radiation (60 Gy in 30 fractions) and temozolomide (TMZ) (75 mg/m2/day). Everolimus was escalated from 2.5 (Dose Level 1), to 5 (Dose Level 2), to 10 mg/day (Dose Level 3). Maintenance TMZ was delivered at 150-200 mg/m2 on days 1 to 5 every 28 days for up to 12 cycles with concurrent everolimus at the previously established daily dose of 10 mg/day. Dose escalation continued if a dose level produced DLTs in ≤ 2 of the first 6 evaluable patients. Results: Between October 28, 2010 and July 2, 2012, the Radiation Therapy Oncology Group (RTOG) 0913 protocol initially registered a total of 35 patients, with 25 patients successfully meeting enrollment criteria, receiving drug and evaluable for toxicity. Everolimus was successfully escalated to the predetermined MTD of 10 mg/day. Two of the first 6 eligible patients experienced a DLT at each dose level. DLTs included: gait disturbance, febrile neutropenia, rash, fatigue, thrombocytopenia, hypoxia, ear pain, headache, and mucositis. Other common toxicities were Grade 1/2 hypercholesterolemia and hypertriglyceridemia. At the time of analysis, there was one death reported, which was attributed to tumor progression. Conclusions: Daily oral everolimus (10 mg) combined with both concurrent radiation therapy and TMZ followed by maintenance TMZ, is well tolerated, with an acceptable toxicity profile. A phase II randomized clinical trial with mandatory correlative biomarker analysis is currently underway, designed to both determine the efficacy of this regimen and identify molecular determinants of response. Supported by RTOG U10 CA21661 and CCOP U10 CA37422 grants from NCI and Novartis. Clinical trial information: NCT01062399.
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