A phase II double-blind, randomized clinical trial assessing the tolerability of two different ratios of cannabis in patients with glioblastoma multiforme (GBM).

Abstract

2530Background: Cannabis has been used for cancer-related symptoms but few trials have assessed quality of life or tolerability, and trials assessing tumour response or survival remain scarce. Treatment for recurrent glioblastoma (rGBM) remains palliative with poor prognosis. The tolerability of THC-containing cannabis products, and their effect on symptoms and quality of life in people with rGBM patients is poorly defined but is essential before efficacy trials can be conducted. Methods: We conducted a randomised double-blinded trial assessing the tolerability of two preparations of cannabis in 88 people with rGBM. The two preparations used different cannabidiol (CBD) to tetrahydrocannibidiol (THC) ratios; 1:1 (5.8mg/ml:5.6mg/ml) and 1:4 (3.8mg/ml:15mg/ml). Daily evening doses were individually monitored and titrated. Outcomes included disease response by FACT-Br, MRI imaging 12 weekly, blood pathology, NCI-CTC and clinical monitoring. Symptom assessments were performed 4 weekly for 12 weeks. Results: 921 people volunteered for screening across Australia, with 642 excluded, 92 recruited with 88 enrolled. 61 participants completed 12-week follow-up (attrition 30%). Both cannabis oils were well tolerated. Total FACT-Br was similar for both preparations, however, statistical significance was found for the physical section (p = 0.025) and functional (p = 0.014) identifying the 1:1 ratio as the more appropriate combination. Comparing groups to baseline, participants reported improvement of sleep (p = 0.009), improved energy (p = 0.015), and contentment with QoL (p = 0.006). Total cohort compared to baseline, participants reported improvement of sleep (p = 0.0001), pain (p = 0.046), nausea (p = 0.017), anxiety (p = 0.005) and seizure activity (p = 0.022). There were no major adverse events attributable to the cannabis with main side effects noted as dizziness, drowsiness, tiredness, and dry mouth. No abnormal blood pathology nor variance in NCI-CTCAE scores were observed. Conclusions: A single nightly dose of THC-containing cannabis was well tolerated in patients in both groups with rGBM and significantly improved sleep and functional wellbeing and QOL in a sample of patients compared to baseline. From this trial, the 1:1 ratio has been identified as the better tolerated product with suprerior symptom and QoL outcomes compared to the 1:4 product. Clinical trial information: ACTRN12617001287325 .