Oral THC:CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting (CINV): a randomised, placebo-controlled, phase 2 crossover trial

Background: This multi-centre, randomised, double-blinded, placebo-controlled, phase 2/3 trial is aimed to evaluate an oral THC:CBD cannabis extract for prevention of refractory CINV. Here we report the phase 2 component results.

Patients and methods: Eligible patients experienced CINV during moderate-highly emetogenic intravenous chemotherapy despite guideline-consistent anti-emetic prophylaxis. Study treatment consisted of 1 cycle of 1-4 self-titrated capsules oral THC 2.5mg/CBD 2.5mg (TN-TC11M) three times daily, days -1 to 5 and 1 cycle of matching placebo in a crossover design, then blinded patient preference for a 3^rd cycle. The primary endpoint was the proportion of participants with complete response during 0-120 hours from chemotherapy. 80 participants provided 80% power to detect a 20% absolute improvement with a 2-sided p-value of 0.1.

Results: 81 participants were randomised; 72 completing 2 cycles are included in the efficacy analyses and 78 not withdrawing consent are included in safety analyses. Median age was 55 years (range 29-80). 78% were female. Complete response was improved with THC:CBD from 14% to 25% (RR 1.77, 90% CI 1.12, 2.79, P=0.041), with similar effects on absence of emesis, use of rescue medications, absence of significant nausea, and summary scores for the Functional Living Index-Emesis (FLIE). 31% experienced moderate or severe cannabinoid-related adverse events such as sedation, dizziness, disorientation; but 83% of participants preferred cannabis to placebo. No serious adverse events were attributed to THC:CBD.

Conclusion: The addition of oral THC:CBD to standard anti-emetics was associated with less nausea and vomiting but additional side effects. Most participants preferred THC:CBD to placebo. Based on these promising results, we plan to recruit an additional 170 participants to complete accrual for the definitive, phase 3, parallel group analysis.

Keywords: antiemetic; cannabidiol; cannabis; chemotherapy-induced nausea and vomiting; randomized trial.