Up to half of patients receiving chemotherapy of moderate or high emetic risk experience CINV despite optimal anti-emetic prophylaxis. Limited evidence suggests cannabinoid medicine in the form of tetrahydrocannabinol (THC) may reduce CINV, and addition of cannabidiol (CBD) may improve efficacy and tolerance. The aim of this multi-centre, randomised, placebo-controlled, phase II/III trial is to determine efficacy and cost-effectiveness of addition of an oral cannabinoid-rich THC/CBD cannabis extract for control of CINV.
The target population is adult patients experiencing CINV during moderate and highly emetogenic chemotherapy regimens despite appropriate anti-emetic therapy, who are scheduled to receive at least 2 more consecutive cycles (A, B and, where applicable, C). Treatment consists of oral THC 2.5mg/CBD 2.5mg (Tilray TN-TC11M) capsules or placebo TDS days -1 to 5, in addition to guideline-consistent anti-emetics, including rescue medications. Patients will start with 1 tablet PO TDS and can dose-titrate to a maximum of 4 tables PO TDS based on nausea control and side-effects. In the pilot trial (N = 80), subjects are randomised for cycle A, cross-over for cycle B, and nominate preferred treatment for cycle C. The planned definitive trial (N = 250) will randomise subjects to investigational product or placebo for cycles A, B and C in a parallel design. The primary end-point is the proportion of patients gaining a complete response (no emesis and no use of rescue medications) (0 – 120h), with additional end-points of (i) complete response, (ii) no emesis, (iii) no significant nausea and (iv) no use of rescue medication during the a) acute, b) delayed, and c) overall phases of cycle A, B and C, (iv) adverse events, (v) quality of life, and (vi) cost-effectiveness. As of 09/05/2018, 52 of 80 patients have been recruited to the pilot study, with expected recruitment completion in 3rd quarter 2018. Funding: NSW Department of Health. Acknowledgements: Trial participants, investigators and research staff. Drug supply by Tilray.
Clinical trial identification
Legal entity responsible for the study
University of Sydney.
New South Wales Department of Health.
A. Tognela: Travel, accommodation, expenses: Merck Serono. P.S. Haber: Stock/Membership: Cleveland Biolab; Honoraria, advisory board, HCV drugs: Gilead; Research funding: Braeburn (opioid product clinical trial). M. Stockler: Research funding: Astellas Pharma, Celgene, Bayer, Bionomics, Medivation, Sanofi, Pfizer, AstraZeneca, Bristol-Myers Squibb, Roche, Amgen, Merck Sharpe & Dohme, Tilray; Travel, accommodation, expenses: Medivation/Pfizer. N. Lintzeris: Consulting/advisory role: Mundipharma International, Indivumed; Research funding: Braeburn Pharmaceuticals (to institution). J. Simes: Research grants to institution: Abbvie, AGITG, Amgen, ANZ Breast Cancer Trials Group, Astellas Pharma, Bayer Pharmaceuticals, BBI, Bristol-Myers Squibb, Cancer Australia, Cancer Institute NSW, Cure Brain Cancer Foundation, Merck-Serono, MSD, NHMRC, Novartis, Pfizer, Roche. I. McGregor: Patents, royalties, other IP: University of Sydney, Kinoxis Therapeutics. I. Olver: Research funding: MSD, Jansen. C. Gedye: Employment: Novotec CRO; Research funding: CPI for co-operative group trials supported by BMS and MSD. R.L. Morton: Honoraria: Amgen, Baxter Healthcare; Research funding: Edwards Life Sciences. P. Grimison: Research funding to institution: Tilray, Pfizer, MSD, Gilead Sciences, Boston Biochemical, Tigermed; Personal research funding: Specialised Therapeutics, Progen, Medimmune. All other authors have declared no conflicts of interest.