Cannabis extract for secondary prevention of chemotherapy-induced nausea and vomiting: Results of a phase II/III, placebo-controlled, randomised trial.

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12019 Background: The aim of this multi-centre, randomised, placebo-controlled, phase II/III trial was to determine the efficacy of adding an oral THC/CBD (tetrahydrocannabinol/cannabidiol) cannabis extract in adults who experience CINV during moderate and highly emetogenic intravenous chemotherapy regimens despite guideline-consistent anti-emetic prophylaxis. The phase II crossover component has been published (Grimison et al, AnnOnc 2020). Here we report the definitive results from the combined phase II/III components with a planned sample size of 250 patients. Methods: For the definitive phase III component, participants were randomised 1:1 to receive, oral THC 2.5mg/CBD 2.5mg (Tilray TN-TC11M) capsules TDS days -1 to 5, or placebo (in addition to guideline-consistent anti-emetics including rescue medications) for cycles A, B and C. Primary endpoint was the difference in gaining a ‘complete response’ (no emesis and no use of rescue medications) during 0-120 hours from chemotherapy for cycle A. Results: Complete response was achieved in 24% and 8% with THC/CBD and placebo, respectively (absolute difference 16%, P-value 0.01). The study closed early due to slow accrual without knowledge of study outcomes, with a total of 147 patients recruited 2016-22 (pilot n=78, definitive n=69). Median age was 56 years (range 25 to 80), 78% were females, 39% reported historic cannabis use, 65% were treated with curative intent. Most common regimens were doxorubicin/cyclophosphamide (AC, 31%), and fluorouracil/oxaliplatin (FOLFOX, 17%), 97% received corticosteroid & 5-HT3 antagonist, 80% received NK-1 antagonist, 10% received olanzapine. Efficacy and safety are shown in the table. No SAEs were attributed to THC/CBD. Conclusions: Oral THC/CBD was associated with a significant increase in the proportion of patients achieving a complete response in chemotherapy-induced nausea and vomiting and was well tolerated, representing an effective new treatment in the management of this condition. Future analyses will report quality of life and cost-effectiveness. Funding from NSW Government Dept of Health. Drug supply by Tilray. Clinical trial information: ACTRN12616001036404 . [Table: see text]