A Phase 2 Randomised, Double Blind Clinical Trial Assessing the Tolerability of Two Different Ratios of Medicinal Cannabis in Patients with Glioblastoma Multiforme (GBM)

Abstract

Background: Glioblastoma (GBM) remains incurable. Patients seek complementary treatments when standard treatments are ineffective, or when cancer symptoms are uncontrolled. Cannabis has intense interest as both therapy and palliation for GBM, but little prospective controlled data exists. We studied the safety and tolerability of two different quality-assured medicinal cannabis preparations in patients with GBM, taking standard treatments. Patients and Methods: Patients with recurrent high-grade glioma (anaplastic astrocytoma or GBM) with no history of substance abuse enrolled in a single-centre phase II double-blind randomized clinical trial comparing two preparations of medicinal cannabis (tetrahydrocannabinol (THC) to cannabidiol (CBD), THC 1:1 CBD and THC 4:1 CBD) taken once daily at night. Retrospective historically matched controls were audited from clinical records as comparators. Results: Patient self-referral for screening was overwhelming (n=921). Both preparations were well tolerated. Side effects included dry mouth, tiredness at night, dizziness, drowsiness, and impaired motor coordination, but no serious adverse events were attributable to the intervention. Sleep was reported as improved from baseline in both groups (95% CI 2.4-2.77; p=0.009). Overall quality of life (FACT-Br) was improved from baseline in both groups with the 1:1 preparation favouring both physical (95% CI 6.49-7.92; p=0.025) and functional (95% CI 15-16.9; p=0.014) capacity. Disease control appeared no worse than historical controls; only 10% of patients experienced progressive disease during the study period, and median overall survival was 11 months. Conclusion: A single nightly dose of medicinal cannabis was safe, well tolerated and appeared to improve sleep, functional wellbeing and quality of life (QOL) compared to baseline, with no negative impact on disease control. The 1:1 preparation is favoured for future studies in people with high-grade brain cancer. Trial Registration: The trial protocol was registered with the Australian New Zealand Clinical Trial Registry (ANZCTR): ACTRN12617001287325. Funding Statement: The funding body, Bioceuticals Pty Ltd, had no involvement with the protocol development, implementation of the trial, collection nor analysis of the trial. The trial was conducted by an independent research institution, Endeavour College of Natural Health which was the initial sponsor for the trial which has now been transferred to Southern Cross University (SCU) due to the lead researcher transferring universities. The funding body paid fees directly to Endeavour and SCU for the trial and supplied the investigational products for the trial in kind Declaration of Interests: All investigators declare no conflict of interest with this study. Prof Charlie Teo and Dr Mike Sughrue are shareholders and founders of Omniscient neurotechnologies for brain tumours but does not conflict with this study. Ethics Approval Statement: The trial was approved by human research ethical committees (HREC), South Eastern Sydney Local Health District HREC: 18/028, University of Technology Sydney HREC: ETH 18-2761 and Endeavour College of Natural Medicine HREC: 20180821.