Background: The aim of this multi-centre, randomised, double-blinded, placebocontrolled, phase 2/3 trial is to determine efficacy of addition of oral cannabis in adults with any malignancy of any stage, experiencing CINV during moderate-highly emetogenic intravenous chemotherapy, despite guideline-consistent anti-emetic prophylaxis, requiring ≥ 2 chemotherapy cycles. Here we report the crossover phase 2 component results
Methods: Treatment consisted of 1 cycle of oral THC 2.5mg/CBD 2.5mg (TN-TC11M) capsules tds days -1 to 5 and 1 cycle matching placebo in a crossover design, then blinded patient preference for a 3 cycle. Primary end-point is difference in proportion of patients with ‘complete response’ (no emesis & no use of rescue medications) during 0-120 hours from chemotherapy between cycles. 80 patients provides 80% power with 2p of 0.1 to detect a 20% difference.
Results: 81 patients recruited (2016-9). 72 completing 2 cycles are included in efficacy analyses. 78 not withdrawing consent are included in safety analyses. Median age was 55 years (range 29-80), 78% were female, 42% report historic cannabis use, 55% were treated with curative intent. Most common regimens were AC (26%), FOLFOX (17%). All received steroids & 5-HT3 antagonist, 79% received NK-1 antagonist, 4% received olanzapine. Efficacy is shown in table. 83% preferred cannabis to placebo. Most common bothersome cannabinoid-related adverse events (cannabis, placebo) were sedation (19%,4%), dizziness (10%,1%), disorientation (3%,0%). No SAEs were attributed to THC/CBD.
Conclusions: Addition of oral THC/CBD to standard anti-emetics was associated with less nausea & vomiting but additional side effects. Most preferred THC/CBD to placebo. Based on these positive results, the definitive parallel phase 3 trial component continues (additional n = 170).
|ENDPOINTS||THC/CBD* %||PLACEBO* %||Difference %
|Complete response||25||14||11 (3,19)||0.04|
|No emesis||69||57||12 (2,23)||0.05|
|No significant nausea**||21||10||11 (3,19)||0.03|
|No use of rescue medications 28 15||28||15||13 (3,22)||0.03|
*n = 72 (crossover design)
** < 2 on 10-point rating scale
Acknowledgements: Trial participants, investigators, research staff. Funding from NSW Government Dept of Health. Drug supply by Tilray. ACTRN12616001036404.