Pilot and definitive randomised double-blind placebo-controlled trials evaluating an oral cannabinoid-rich THC/CBD cannabis extract for secondary prevention of chemotherapy-induced nausea and vomiting (CINV)

Abstract

Background: 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. Trial design: 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 TNTC11M) capsules or placebo TDS days‐1 to 5, in addition to guideline‐consistent antiemetics, 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 endpoints 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.