e-Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2020

Results of crossover phase 2 component of randomised placebo-controlled trial evaluating oral THC/CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting (CINV) (#415)

Peter S. Grimison 1 , Martin R. Stockler 2 , Adrienne Kirby 2 , Anna Walsh 2 , Nicholas Lintzeris 3 , Yvonne Cheung 2 , Antony Mersiades 2 , Annette Tognela 4 , Paul Haber 5 , John Simes 2 , Rachael L. Morton 6 , Ian N. Olver 7 , Iain McGregor 8 , Craig Gedye 9 , Peter Fox 10 , Karen P. Briscoe 11 , Morteza Aghmesheh 12 , Ehtesham A. Abdi 13 , Stephen Della-Fiorentina 14
  1. Chris O'Brien Lifehouse, Sydney, Australia
  2. NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia
  3. Drug and Alcohol Services, South East Sydney Local Health District, Concord, Australia
  4. Campbelltown Hospital, Campbelltown, Australia
  5. Sydney Medical School, University of Sydney, Camperdown, NSW, Australia
  6. Melanoma Institute Australia, NHMRC Clinical Trials Centre, The University of Sydney, Sydney, Australia
  7. University of Adelaide, Adelaide, SA, Australia
  8. Lambert Initiative for Cannabinoid Therapeutics, University of Sydney, Camperdown, Australia
  9. Calvary Mater Newcastle, Waratah, Australia
  10. Royal Prince Alfred Hospital, Annandale, Australia
  11. Mid North Coast Cancer Institute, Mid North Coast Local Health District, Coffs Harbour, Australia
  12. Illawarra Cancer Care Centre, Illawarra Shoalhaven Local Health District, Wollongong, Australia
  13. Griffith University Gold Coast, The Tweed Hospital, Tweed Heads, Australia
  14. Southern Highlands Cancer Centre, Bowral, NSW, Australia

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 %
(90% CI)		 p-value
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.