Oral cannabinoid-rich THC/CBD cannabis extract for secondary prevention of chemotherapy-induced nausea and vomiting: a study protocol for a pilot and definitive randomised double-blind placebo-controlled trial (CannabisCINV)

Antony J Mersiades; Annette Tognela; Paul S Haber; Martin Stockler; Nicholas Lintzeris; John Simes; Iain McGregor; Ian Olver; David J Allsop; Craig Gedye; Adrienne C Kirby; Rachael L Morton; Peter Fox; Stephen Clarke; Karen Briscoe; Morteza Aghmesheh; Nicole Wong; Anna Walsh; Carmel Hahn; Peter Grimison

doi:10.1136/bmjopen-2017-020745

Oral cannabinoid-rich THC/CBD cannabis extract for secondary prevention of chemotherapy-induced nausea and vomiting: a study protocol for a pilot and definitive randomised double-blind placebo-controlled trial (CannabisCINV)

BMJ Open. 2018 Sep 12;8(9):e020745. doi: 10.1136/bmjopen-2017-020745.

Authors

Antony J Mersiades¹, Annette Tognela², Paul S Haber^{3

4}, Martin Stockler^{1

5}, Nicholas Lintzeris^{3

6}, John Simes^{1

7}, Iain McGregor⁸, Ian Olver⁹, David J Allsop⁸, Craig Gedye¹⁰, Adrienne C Kirby¹, Rachael L Morton¹, Peter Fox¹¹, Stephen Clarke^{12

13}, Karen Briscoe¹⁴, Morteza Aghmesheh¹⁵, Nicole Wong¹, Anna Walsh¹, Carmel Hahn⁷, Peter Grimison^{1

7}

Affiliations

¹ NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia.
² Macarthur Cancer Therapy Centre, Campbelltown Hospital, Sydney, New South Wales, Australia.
³ Discipline of Addiction Medicine, University of Sydney, Sydney, New South Wales, Australia.
⁴ Drug Health Services, Sydney Local Health District, Sydney, New South Wales, Australia.
⁵ Department of Medical Oncology, Concord Cancer Care Centre, Concord Hospital, Sydney, New South Wales, Australia.
⁶ Drug and Alcohol Services, South East Sydney Local Health District, Sydney, New South Wales, Australia.
⁷ Department of Medical Oncology, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia.
⁸ Lambert Initiative for Cannabinoid Therapeutics, University of Sydney, Sydney, New South Wales, Australia.
⁹ University of South Australia Cancer Research Institute, University of South Australia, Adelaide, South Australia, Australia.
¹⁰ Department of Medical Oncology, Calvary Mater Newcastle, Newcastle, New South Wales, Australia.
¹¹ Central West Cancer Care Centre, Orange Health Service, Orange, New South Wales, Australia.
¹² Department of Medical Oncology, Royal North Shore Hospital, Sydney, New South Wales, Australia.
¹³ Bill Walsh Cancer Research Laboratory, Kolling Institute of Medical Research, Sydney, New South Wales, Australia.
¹⁴ Mid North Coast Cancer Institute, Coffs Harbour Hospital, Coffs Harbour, New South Wales, Australia.
¹⁵ Illawarra Shoalhaven Cancer and Haematology Network, Wollongong Hospital, Wollongong, New South Wales, Australia.

Abstract

Introduction: Chemotherapy-induced nausea and vomiting (CINV) remains an important issue for patients receiving chemotherapy despite guideline-consistent antiemetic therapy. Trials using delta-9-tetrahydrocannabinol-rich (THC) products demonstrate limited antiemetic effect, significant adverse events and flawed study design. Trials using cannabidiol-rich (CBD) products demonstrate improved efficacy and psychological adverse event profile. No definitive trials have been conducted to support the use of cannabinoids for this indication, nor has the potential economic impact of incorporating such regimens into the Australian healthcare system been established. CannabisCINV aims to assess the efficacy, safety and cost-effectiveness of adding TN-TC11M, an oral THC/CBD extract to guideline-consistent antiemetics in the secondary prevention of CINV.

Methods and analysis: The current multicentre, 1:1 randomised cross-over, placebo-controlled pilot study will recruit 80 adult patients with any malignancy, experiencing CINV during moderate to highly emetogenic chemotherapy despite guideline-consistent antiemetics. Patients receive oral TN-TC11M (THC 2.5mg/CBD 2.5 mg) capsules or placebo capsules three times a day on day -1 to day 5 of cycle A of chemotherapy, followed by the alternative drug regimen during cycle B of chemotherapy and the preferred drug regimen during cycle C. The primary endpoint is the proportion of subjects attaining a complete response to CINV. Secondary and tertiary endpoints include regimen tolerability, impact on quality of life and health system resource use. The primary assessment tool is patient diaries, which are filled from day -1 to day 5. A subsequent randomised placebo-controlled parallel phase III trial will recruit a further 250 patients.

Ethics and dissemination: The protocol was approved by ethics review committees for all participating sites. Results will be disseminated in peer-reviewed journals and at scientific conferences.

Drug supply: Tilray.

Protocol version: 2.0, 9 June 2017.

Trial registration number: ANZCTR12616001036404; Pre-results.

Keywords: antiemetic; cannabidiol; cannabis; chemotherapy-induced nausea and vomiting; randomized trial.

Publication types

Clinical Trial Protocol
Research Support, Non-U.S. Gov't

MeSH terms

Administration, Oral
Antineoplastic Agents / adverse effects*
Cannabidiol / economics
Cannabidiol / therapeutic use*
Cannabinoid Receptor Agonists / economics
Cannabinoid Receptor Agonists / therapeutic use*
Cost-Benefit Analysis
Double-Blind Method
Dronabinol / economics
Dronabinol / therapeutic use*
Drug Combinations
Humans
Multicenter Studies as Topic
Nausea / chemically induced
Nausea / prevention & control*
Patient Reported Outcome Measures
Phytotherapy* / economics
Pilot Projects
Randomized Controlled Trials as Topic
Secondary Prevention*
Vomiting / chemically induced
Vomiting / prevention & control*

Substances

Antineoplastic Agents
Cannabinoid Receptor Agonists
Drug Combinations
TN-TC11M
Cannabidiol
Dronabinol

Associated data

ANZCTR/ANZCTR12616001036404