Mebendazole plus lomustine or temozolomide in patients with recurrent glioblastoma: A randomised open-label phase II trial.
rct · Level II
Where this comes from
- Record sourced from PubMed, PMID 35747192.
- Also identified by DOI 10.1016/j.eclinm.2022.101449 and PMC identifier 9156991.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Recurrent glioblastoma (GBM) has dismal outcomes and limited treatment options. Mebendazole (MBZ) has activity in glioma both <i>in-vivo</i> and <i>in-vitro</i>, and is well tolerated in combination with lomustine (CCNU) and temozolomide (TMZ). In this study, we sought to determine whether the addition of MBZ to CCNU or TMZ would improve overall survival (OS) in recurrent GBM. In this phase II randomized open-label trial, adult patients with ECOG PS 0-3, with recurrent GBM who were not eligible for re-radiation, were randomized 1:1 to the CCNU-MBZ and TMZ-MBZ arms. CCNU was administered at 110 mg/m<sup>2</sup> every 6 weeks with MBZ 800 mg thrice daily and TMZ was administered at 200 mg/m<sup>2</sup> once daily on days 1-5 of a 28 days cycle with MBZ 1600 mg thrice daily. The primary endpoint was OS at 9 months. A 9-month OS of 55% or more in any arm was hypothesized to warrant further evaluation and a value below 35% was too low to warrant further investigation. OS was analyzed using intention to treat (ITT) and per-protocol (PP) analyses. Per-protocol analysis was used for safety analysis. Clinical Trials Registry-India number, CTRI/2018/01/011542. Participants were recruited from 14<sup>th</sup> March 2019 to 18<sup>th</sup> June 2021, 44 patients were randomised on each arm. At 17.4 months, 68 events for OS analysis had occurred, 33 in the TMZ-MBZ and 35 in the CCNU-MBZ arm. The 9-month OS was 36.6% (95% CI 22.3-51.0) and 45% (95% CI 29.6-59.2) in the TMZ-MBZ and CCNU-MBZ arms respectively, in the ITT population. ECOG PS was the only independent prognostic factor impacting OS (HR-0.48, 95% CI 0.27-0.85; <i>P</i> = 0.012). Grade 3-5 adverse events were seen in 8 (18.6%; <i>n</i> = 43) and 4 (9.5%; <i>n</i> = 42) patients in the TMZ-MBZ and CCNU-MBZ arms respectively. There were no treatment related deaths. The addition of MBZ to TMZ or CCNU failed to achieve the pre-set benchmark of 55% 9-month OS. This was probably due to 28.6% of patients having poor PS of 2-3. Brain Tumor Foundation (BTF) of India, Indian Cooperative Oncology Network (ICON), and India Cancer Research Consortium (ICRC) under ICMR (Indian Council of Medical Research).