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Trial registered on ANZCTR


Registration number
ACTRN12616001036404
Ethics application status
Approved
Date submitted
18/05/2016
Date registered
4/08/2016
Date last updated
18/02/2019
Date data sharing statement initially provided
18/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
CannabisCINV: A placebo-controlled trial evaluating an oral THC/CBD cannabis extract for secondary prevention of chemotherapy-induced nausea and vomiting in patients of any known malignancy receiving chemotherapy.
Scientific title
CannabisCINV: 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
Secondary ID [1] 288991 0
CTC 0146
Universal Trial Number (UTN)
Trial acronym
CannabisCINV
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chemotherapy induced nausea and vomiting 298396 0
Cancer 299757 0
Condition category
Condition code
Cancer 298495 298495 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Oral capsule containing 2.5mg THC and 2.5mg CBD, derived from Cannabis Sativa L. Extract, containing Delta-9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD) in near-equal amounts.
Frequency and duration of administration: taken once the day before chemotherapy and three times daily for 5 days for the first 5 days of participants' chemotherapy cycle and for three consecutive cycles.
Adherence in monitored by counting the returned capsules and comparing with the amount dispensed less the amount documented to have been ingested by the participant.

Participants enrolled in the pilot phase of the study are excluded from enrollment in the definitive phase.

In the Phase II part of the study, the first two cycles will be a placebo controlled, randomised crossover design, with the third being decided by participant preference.

In the Phase III part of the study will be placebo controlled, randomised parallel design.
Intervention code [1] 294478 0
Treatment: Drugs
Comparator / control treatment
Placebo capsule; HPMC -- Hydroxypropylmethylcellulose capsule containing same excipients as the active capsule but does not contain THC or CBD.
Control group
Placebo

Outcomes
Primary outcome [1] 297985 0
The primary objective is to compare, amongst patients randomised to oral THC/CBD or placebo, the compositie outcome of the ability to control emesis and nausea. This will be assessed using patient reported outcomes recorded in a diary daily for the 6 days of study treatment through each of the three chemotherapy cycles and the completion of the Functional Living Index - Emesis 5 day questionnaire at the end of each cycle.
Timepoint [1] 297985 0
Daily for the 6 days of study treatment through each of the three chemotherapy cycles.
Secondary outcome [1] 322831 0
To compare Cannabinoid-related adverse events amongst patients randomised to oral THC/CBD or placebo.
Participants will be assessed by the study nurse via phone call, daily for the 6 days of study treatment through each of the three chemotherapy cycles, for the following possible adverse events; dizziness, disorientation, hallucinations, anxiety, palpitations and sedation.
Timepoint [1] 322831 0
Participants will be assessed by the study nurse in the clinic on day -1 and via phone call daily for the 5 days of study treatment through each of the three chemotherapy cycles as well as at clinic visits at the end of each cycle and at the follow up visit 30 days after last treatment.
Secondary outcome [2] 322832 0
To compare health-related quality of life amongst patients randomised to oral THC/CBD or placebo using the Functional Living Index - Emesis 5 day (FLIE 5D) and Australian Quality Of Life - 8 dimensions (AQOL-8D) questionnaires.
Timepoint [2] 322832 0
Questionnaires will be completed at baseline and at clinic visits at the end of each cycle and at the follow up visit 30 days after last treatment.
Secondary outcome [3] 322833 0
To compare the regimen’s acceptability amongst patients randomised to oral THC/CBD or placebo.
Phase II study this is assessed by the proportion receiving at least one dose of oral THC/CBD during all 6 x 24 hour periods, as assessed by self-report and pill counts and the proportion preferring oral THC/CBD or placebo, as determined by expressed preference for cycle 1 versus cycle 2 of study treatment.

Phase III study this is assessed by the proportion receiving at least one dose of oral THC/CBD during all 6 x 24 hour periods, as assessed by self-report and pill counts.

Timepoint [3] 322833 0
Phase II study, Participants will complete the dose taken daily for the 6 days of study treatment through each of the three chemotherapy cycles. In addition, participants will complete a preference questionnaire at the end of the second cycle.

Phase III study, Participants will complete the dose taken daily for the 6 days of study treatment through each of the three chemotherapy cycles.
Secondary outcome [4] 322834 0
To compare health system resource use and costs amongst patients randomised to oral THC/CBD or placebo.
This composite outcome will be asssessed as follows: resource use will be identified and measured from trial case report forms (for hospitalisations), and through linkage to Medicare claims data for outpatient visits (MBS) and prescribed medicines (PBS). Australian unit costs will be applied to the resource usage data.
Timepoint [4] 322834 0
Participants will be assessed for hospitalisations in the clinic on day -1 and via phone call daily for the 5 days of study treatment through each of the three chemotherapy cycles as well as at clinic visits at the end of each cycle and at the follow up visit 30 days after last treatment.

Participants will be asked to sign a consent form to allow for MBS and PBS data to be extracted at the time of consent.

Eligibility
Key inclusion criteria
1. Adults, aged 18 years and older, with known malignancy of any stage
2. Receiving intravenous chemotherapy of high or moderate emetic risk as defined by MASCC criteria on Treatment Day 1 administered in cycles of planned duration greater than or equal to 14 days and less than or equal to 21 days
Note:
- Chemotherapy agents classified as low and/or minimal emetic risk may be used concurrently throughout the treatment period (acceptable combination regimens include but not limited to: FOLFOX, carboplatin day 1 and gemcitabine day 1 and 8)
- Multi-day use of chemotherapy of high or moderate emetic risk is permitted up until but not beyond day 5 is permitted, when the continuation of the chemotherapy is part of the overall Day 1 regimen (acceptable multi-day regimens include but not limited to: BEP, TIP; unacceptable multi-day regimens include but not limited to: weekly cisplatin, weekly carboplatin, cisplatin day 1 & 8 with gemcitabine day 1 & 8, MVAC)
- Concurrent oral chemotherapy and radiotherapy are not permitted
3. Requires greater than or equal to 2 further cycles of chemotherapy
4. Experiencing significant CINV during previous cycle 1
- defined as need for rescue medications for vomiting or distress by nausea, and/or greater than or equal to moderate nausea on 5-point rating scale, despite best-practice MASCC guideline-consistent anti-emetic regimen
5. ECOG performance status of 0, 1 or 2
6. Predicted life expectancy of greater than or equal to 4 months
7. Willing and able to comply with all study requirements, including treatment, timing and nature of required assessments including diary, quality of life forms, urine tests, and any mandated blood tests
8. Signed, written informed consent
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Symptomatic primary or secondary CNS malignancy
2. Symptomatic gastrointestinal obstruction
3. Disease-related nausea or vomiting requiring daily anti-emetic therapy
4. Unstable cardiovascular disease (uncontrolled hypertension, unstable ischaemic heart disease, unstable congestive cardiac failure)
5. History of epilepsy or recurrent seizures
6. History of schizophrenia, other psychotic illness, severe personality disorder, suicidal ideation, or other significant psychiatric disorder, other than depression associated with underlying condition
7. Substance use disorder (ICD-10 criteria (abuse, dependence) to alcohol, opioids, benzodiazepines, or illicit stimulants
8. Serious medical or psychiatric condition that might limit the ability of the patient to consent to the study and/or comply with the protocol
9. Scheduled to receive oral chemotherapy during planned duration of study
10. Patient has received or is scheduled to receive radiation therapy to the brain, abdomen or pelvis in the week prior to commencement of study treatment, or during study treatment
11. Is scheduled to receive any investigational drug during the present study
12. Patients using or having used cannabis or cannabinoid based medications within 30 days of study entry and unwilling to abstain for the duration of the study
13. Prior hypersensitivity or intolerable adverse reaction to cannabis or cannabinoid based medications, 5HT3 antagonist, dexamethasone, NK1 antagonist
14. Unwilling to avoid driving or operating machinery during and for 72 hours after taking study medication
15. Concerns regarding safe storage of study medication (eg. unsuitable home environment)
16. Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception.
17. Patients who were previously enrolled in this study and received the study intervention (oral THC/CBD and/or placebo)
18. Patients who declare they have been convicted of a criminal offence.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
This is a double blind study allocation involves contacting the holder of the allocation schedule who is "off-site" or at central administration site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Minimisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Pilot phase II trial is a placebo controlled crossover design for the first two cycles and with the third cycle being decided by preference
Definitive phase III trial is a placebo controlled parallel design
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Pilot Study
The primary analyses will include all patients who were randomised. Missing values will not be imputed. The results will be examined for differential effect in the two periods and if necessary, the data from cycle A will be analysed separately.
The primary outcome is complete response. The primary analysis will be a McNemar’s test. In the event that there is differential drop-out between period, or a period by treatment interaction, the results from the first period will be analysed using a chi-square test. Analyses to assess period by treatment interaction will use Generalised Estimating Equations (GEEs) to account for the correlation within a patient. Secondary analyses to adjust for any baseline variables will also use GEEs. All tests will use a two-sided significance level of 10%.
A sample size of 80 patients utilising a cross-over design, randomising patients to either study drug followed by placebo or placebo followed by study drug, will have 80% power at a 2-sided significance level of 10% to detect a 20% difference in discordant responses (response on one intervention but not the other).

Definitive study
The primary analyses will include all patients who were randomised.
The primary outcome is complete response. The primary analysis will be a chi-square analysis. Secondary analyses adjusting for baseline variables will use GEES. Binary secondary outcomes will be analyses as for the primary outcome. Count data will be analyses using a Generalised Linear Model with a Poisson distribution. Cannabinoid-related adverse events and measures of adherence will be analyses with a chi-square test or two-sample t-test or just listed depending on numbers. All tests will use a two-sided significance level of 5%.
A sample size of 170 patients provides 80% power at 2-sided 5% level of significance to detect improvement in complete response from 22% to 42.5%.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 5606 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment hospital [2] 5607 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [3] 5608 0
Concord Repatriation Hospital - Concord
Recruitment hospital [4] 5610 0
Coffs Harbour Base Hospital - Coffs Harbour
Recruitment hospital [5] 5611 0
Wollongong Hospital - Wollongong
Recruitment hospital [6] 5612 0
Orange Health Service - Orange
Recruitment hospital [7] 6355 0
Nepean Hospital - Kingswood
Recruitment hospital [8] 6357 0
St George Hospital - Kogarah
Recruitment hospital [9] 6440 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [10] 7285 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [11] 7387 0
Port Macquarie Base Hospital - Port Macquarie
Recruitment hospital [12] 13169 0
The Tweed Hospital - Tweed Heads
Recruitment hospital [13] 13170 0
Riverina Cancer Care Centre - Wagga Wagga
Recruitment postcode(s) [1] 13052 0
2050 - Camperdown
Recruitment postcode(s) [2] 13053 0
2298 - Waratah
Recruitment postcode(s) [3] 13054 0
2139 - Concord Repatriation Hospital
Recruitment postcode(s) [4] 13056 0
2450 - Coffs Harbour
Recruitment postcode(s) [5] 13057 0
2500 - Wollongong
Recruitment postcode(s) [6] 13058 0
2800 - Orange
Recruitment postcode(s) [7] 13901 0
2747 - Kingswood
Recruitment postcode(s) [8] 13903 0
2217 - Kogarah
Recruitment postcode(s) [9] 14000 0
2065 - St Leonards
Recruitment postcode(s) [10] 15057 0
2560 - Campbelltown
Recruitment postcode(s) [11] 15180 0
2444 - Port Macquarie
Recruitment postcode(s) [12] 25724 0
2485 - Tweed Heads
Recruitment postcode(s) [13] 25725 0
2650 - Wagga Wagga

Funding & Sponsors
Funding source category [1] 293350 0
Government body
Name [1] 293350 0
Health Administration Corporation, through the NSW Ministry of Health, for and on behalf of the NSW Government
Address [1] 293350 0
73 Miller Street
NORTH SYDNEY NSW 2060
Country [1] 293350 0
Australia
Funding source category [2] 293351 0
Commercial sector/Industry
Name [2] 293351 0
Tilray
Address [2] 293351 0
1100 Maughan Rd, Nanaimo, BC V9X 1J2, Canada
Country [2] 293351 0
Canada
Primary sponsor type
University
Name
University of Sydney
Address
Campderdown NSW 2050
Country
Australia
Secondary sponsor category [1] 292427 0
None
Name [1] 292427 0
Address [1] 292427 0
Country [1] 292427 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294820 0
SLHD Ethics Review Committe RPAH Zone
Ethics committee address [1] 294820 0
RPAH Medical Centre
Suite 210A, 100 Carillon Avenue
NEWTOWN NSW 2042
Ethics committee country [1] 294820 0
Australia
Date submitted for ethics approval [1] 294820 0
06/06/2016
Approval date [1] 294820 0
20/09/2016
Ethics approval number [1] 294820 0
X16-0235

Summary
Brief summary
The primary purpose of this trial is to evaluate the efficacy of an oral capsule containing plant-derived tetrahydrocannbinol (THC) and cannabidiol (CBD) for the prevention of chemotherapy-induced nausea and vomiting (CINV).

Who is it for?
You may be eligible to participate in this trial if you are aged 18 or over and have been diagnosed with any cancer for which you are scheduled to receive at least three further chemotherapy cycles using intravenous chemotherapy of high or moderate emetic risk.

Study details
We will first enrol 80 participants in a pilot trial and if the data from these participants shows the medicine works and is well tolerated, a further 170 participants will be enrolled, this is called the definitive trial.

Participants enrolled in the pilot trial will be randomly allocated (by chance) to receive the study drug for the first five days of their first chemotherapy cycle following enrolment, followed by a placebo capsule for the first five days of the next chemotherapy cycle, or to receive the placebo first followed by the study treatment. All participants will then choose which treatment they would prefer to take for the first five days of the third chemotherapy cycle. Participants will be asked to complete a number of questionnaires relating to their nausea and vomiting, quality of life and any side effects of the treatment.

Participants enrolled in the definitive trial will be randomly allocated (by chance) to receive the study drug or the placebo for the first five days of their next three chemotherapy cycles following enrolment, Participants will be asked to complete a number of questionnaires relating to their nausea and vomiting, quality of life and any side effects of the treatment.

It is hoped that this trial will provide preliminary information on the efficacy of THC and CBD capsules for the prevention of CINV, which will inform further clinical trials.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 64950 0
A/Prof Peter Grimison
Address 64950 0
Organisation: Chris O Brien Lifehouse,

Chris O Brien Lifehouse,
119–143 Missenden Road, Camperdown NSW 2050
Country 64950 0
Australia
Phone 64950 0
+61 2 9562 5000
Fax 64950 0
Email 64950 0
cannabiscinv@ctc.usyd.edu.au
Contact person for public queries
Name 64951 0
Ms Nicole Wong
Address 64951 0
Organisation: University of Sydney

NHMRC CTC,
Level 6 Chris O Brien Lifehouse,
119–143 Missenden Road, Camperdown NSW 2050
Country 64951 0
Australia
Phone 64951 0
+61295625000
Fax 64951 0
Email 64951 0
cannabisCINV@ctc.usyd.edu.au
Contact person for scientific queries
Name 64952 0
Ms Nicole Wong
Address 64952 0
Organisation: University of Sydney

NHMRC CTC,
Level 6 Chris O Brien Lifehouse,
119–143 Missenden Road, Camperdown NSW 2050
Country 64952 0
Australia
Phone 64952 0
+61295625000
Fax 64952 0
Email 64952 0
cannabisCINV@ctc.usyd.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Confidentiality of patients.
What supporting documents are/will be available?
No other documents available
Summary results
No Results