skip to main content

Title: RTOG 0913: A Phase 1 Study of Daily Everolimus (RAD001) in Combination With Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma

Purpose: To determine the safety of the mammalian target of rapamycin inhibitor everolimus (RAD001) administered daily with concurrent radiation and temozolomide in newly diagnosed glioblastoma patients. Methods and Materials: Everolimus was administered daily with concurrent radiation (60 Gy in 30 fractions) and temozolomide (75 mg/m{sup 2} per day). Everolimus was escalated from 2.5 mg/d (dose level 1) to 5 mg/d (dose level 2) to 10 mg/d (dose level 3). Adjuvant temozolomide was delivered at 150 to 200 mg/m{sup 2} 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/d. Dose escalation continued if a dose level produced dose-limiting toxicities (DLTs) in fewer than 3 of the first 6 evaluable patients. Results: Between October 28, 2010, and July 2, 2012, the Radiation Therapy Oncology Group 0913 protocol initially registered a total of 35 patients, with 25 patients successfully meeting enrollment criteria receiving the drug and evaluable for toxicity. Everolimus was successfully escalated to the predetermined maximum tolerated dose of 10 mg/d. Two of the first 6 eligible patients had a DLT at each dose level. DLTs included gait disturbance, febrile neutropenia, rash, fatigue, thrombocytopenia, hypoxia, earmore » pain, headache, and mucositis. Other common toxicities were grade 1 or 2 hypercholesterolemia and hypertriglyceridemia. At the time of analysis, there was 1 death reported, which was attributed to tumor progression. Conclusions: Daily oral everolimus (10 mg) combined with both concurrent radiation and temozolomide followed by adjuvant temozolomide is well tolerated, with an acceptable toxicity profile. A randomized phase 2 clinical trial with mandatory correlative biomarker analysis is currently under way, designed to both determine the efficacy of this regimen and identify molecular determinants of response.« less
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [5] ;  [6] ;  [7] ;  [8]
  1. Department of Radiation Oncology, Experimental Therapeutics and Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center, Tampa, Florida (United States)
  2. Radiation Therapy Oncology Group, Philadelphia, Pennsylvania (United States)
  3. Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (United States)
  4. Department of Pathology, Medical College of Georgia, Augusta, Georgia (United States)
  5. Radiation Oncology, US Oncology-Willamette Valley Cancer Institute, Eugene, Oregon (United States)
  6. Department of Radiation Oncology, Rhode Island Hospital, Providence, Rhode Island (United States)
  7. Department of Radiation Oncology, Tel Aviv Medical Center, Tel Aviv (Israel)
  8. Department of Radiation Oncology, University of Maryland, Baltimore, Maryland (United States)
Publication Date:
OSTI Identifier:
22267831
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 86; Journal Issue: 5; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANOXIA; AUDITORY ORGANS; BIOLOGICAL MARKERS; CLINICAL TRIALS; DEEP LEVEL TRANSIENT SPECTROSCOPY; DIAGNOSIS; FATIGUE; GLIOMAS; PAIN; PATIENTS; RADIATION DOSES; RADIOTHERAPY; TOXICITY