Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000419763p
Ethics application status
Submitted, not yet approved
Date submitted
24/02/2022
Date registered
11/03/2022
Date last updated
11/03/2022
Date data sharing statement initially provided
11/03/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating the effect of medicinal cannabis on the symptoms and side effects of chemotherapy in people with cancer.
Scientific title
The CANnabinoids in CANcer (CANCAN) trial: Investigating the effect of medicinal cannabis on symptoms and side effects of chemotherapy in people with cancer
Secondary ID [1] 306517 0
MRFF: 2001877
Universal Trial Number (UTN)
U1111-1274-9312
Trial acronym
CANCAN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
cancer 325387 0
chemotherapy treatment side effects 325388 0
mucositis 325389 0
diarrhea 325390 0
sleep disturbances 325391 0
anorexia 325392 0
Condition category
Condition code
Cancer 322769 322769 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Brief name: Medicinal cannabis (Cannabidiol [CBD] and Tetrahydrocannabinol [THC])
Status: Unregistered drug
CBD dose: 400 mg/day
THC dose: 2.5-22.5mg/day (starting at 2.5mg increasing at 5mg increments until maximum tolerate dose is achieved in the absence of agitation and sedation (determined by Richmond Agitation and Sedation Scale); each participant escalates with support of nurse who then records final dose).
Duration: 6-9 weeks depending on specifics of cancer treatment schedule
Administration: Oral capsule with medicinal cannabis isolates in oil carrier
Timing of intervention: Solid tumours - from mucositis daily questionnaire (MDQ) score >1 in first cycle of chemotherapy to end of cycle 3. Haematopoeitic stem cell transplant (HSCT) recipients - from day of admission (~day -7) to day +35.
Adherence assessment: participant reported (daily confirmation of taking the capsule) and return of empty capsule packets to hospital pharmacy
Intervention code [1] 322946 0
Prevention
Intervention code [2] 322995 0
Treatment: Drugs
Comparator / control treatment
Placebo (identical capsule with oil carrier only)
Control group
Placebo

Outcomes
Primary outcome [1] 330573 0
Gut distress determined by the Mucositis Daily Questionnaire (MDQ) for up to 3 cycles of chemotherapy and calculated as area under the curve and adjusted per cycle (AUC MDQ/cycle)
Timepoint [1] 330573 0
The MDQ is assessed daily for the duration of each treatment cycle up to a maximum of 3 full cycles. AUC for solid tumour patients will be assessed over the 3rd full cycle of chemotherapy after starting medicinal cannabis. AUC for HSCT participants will be assessed from day 0 to day 21 post-HSCT.
Primary outcome [2] 330574 0
Gut distress determined by plasma citrulline.
Timepoint [2] 330574 0
Solid tumours: Assessed on Day 7+/-1 of each chemotherapy cycle. The primary timepoint will be defined as Day 7+/-1 of the 3rd cycle after commencing medicinal cannabis.
HSCT recipients: Assessed weekly between day -7 and +35 post HSCT. The primary time point will be defined as day 21 post-HSCT.
Secondary outcome [1] 406727 0
Body weight assessed using electronic scales (kg)
Timepoint [1] 406727 0
Assessed weekly for the duration of medicinal cannabis treatment, then at the completion of medicinal cannabis treatment, and at 6 months after starting medicinal cannabis.
Secondary outcome [2] 406728 0
Functional wellbeing determined by the Functional Assessment of Anorexia/Cachexia Treatment (FAACT)
Timepoint [2] 406728 0
Assessed weekly for the duration of medicinal cannabis treatment, then at the completion of medicinal cannabis treatment, and at 6 months after starting medicinal cannabis.
Secondary outcome [3] 406729 0
Symptom burden determined using the Edmonton Symptom Assessment Survey (ESAS) revised to include Sleep and Constipation (ESAS-r-SC)
Timepoint [3] 406729 0
Assessed daily from commencing medicinal cannabis to completion of medicinal cannabis and at 6-month follow up
Secondary outcome [4] 406730 0
Anxiety and depression assessed using the Hospital Anxiety and Depression Scale (HADS)
Timepoint [4] 406730 0
Assessed at baseline, completion of medicinal cannabis at 6 month follow up.
Secondary outcome [5] 406731 0
Quality of life assessed using the EORTC-CLC-Q30
Timepoint [5] 406731 0
Assessed at baseline, completion of medicinal cannabis at 6 month follow up.
Secondary outcome [6] 406732 0
Use of supportive care interventions (e.g. use of rescue medication, emergency department presentations, days in hospital) assessed through hospital presentations and patient reported use.

Timepoint [6] 406732 0
Assessed throughout entire study duration, from commencing medicinal cannabis to 6 month follow up.
Secondary outcome [7] 407038 0
Incidence of dose reductions recorded directly from medical records
Timepoint [7] 407038 0
Assessed at 6 month follow up
Secondary outcome [8] 407039 0
Cumulative dose of chemotherapy accessed directly through medical records.
Timepoint [8] 407039 0
Assessed at 6 month follow up
Secondary outcome [9] 407040 0
Safety defined by occurrence of liver toxicity (determined at each chemotherapy infusion via routine MBA20)
Timepoint [9] 407040 0
Solid tumour: Assessed at each chemotherapy infusion for 3 cycles
HSCT recipients: Weekly as in-patient
Secondary outcome [10] 407166 0
Safety defined by occurrence of adverse events (dizziness, dry mouth, confusion, hallucinations) as reported by the participant via weekly questionnaire. These questions have been added to the Edmonton Symptom Assessment Scale (ESAS), included as additional parameters which can be scored based on severity from 0-10.
Timepoint [10] 407166 0
Assessed weekly for the duration of medicinal cannabis treatment, then at the completion of medicinal cannabis treatment, and at 6 months after starting medicinal cannabis.
Secondary outcome [11] 407167 0
Tumour response determined by CT scan (solid tumour) or equivalent blood based marker (e.g. M-protein for myeloma) for HSCT recipients recorded directly from medical records.
Timepoint [11] 407167 0
CT scan performed at baseline and 12 weeks after diagnosis and bloods assessed at diagnosis and 3- and 6- months after diagnosis.
Secondary outcome [12] 407168 0
Survival determined by overall survival (OS) recorded directly from medical records.
Timepoint [12] 407168 0
6 months, 12 months and 24 months after starting medicinal cannabis
Secondary outcome [13] 407169 0
Relapse determined by progression free survival (PFS) recorded directly from medical records
Timepoint [13] 407169 0
6 months, 12 months and 24 months after starting medicinal cannabis
Secondary outcome [14] 407170 0
Treatment related mortality recorded directly from medical records
Timepoint [14] 407170 0
6 months, 12 months and 24 months after starting medicinal cannabis

Eligibility
Key inclusion criteria
18 years of age or older
Scheduled to receive mucotoxic, systemic cancer therapy for advanced solid and haematological cancers.
Anticipated to undergo 3 cycles of chemotherapy (solid tumour cancer participants) OR autologous stem cell transplantation (haematological cancers – HSCT participants).
Willing to commit to not taking cannabis in any other form during the clinical trial period.
For randomisation of solid tumour participants: Gut distress symptoms related to their cancer therapy defined by a score of greater or equal to 1 in the MDQ and confirmed by research nurse.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Cannabis dependence / misuse defined by the revised Cannabis Use Disorder Identification test score of 8 or above.
History of unstable cardiovascular disease including myocardial infarction or cerebrovascular accident, crescendo history of angina or heart failure.
Recreational or medicinal cannabis use defined as use >once/week in the month leading up to the clinical trial period.
History of psychosis secondary to, or intolerance to cannabis products.
Presence of an active psychiatric disorder or concurrent disorder that may be exacerbated by
cannabinoids, or which may interfere with clinical trial outcome determination (determined by the recruiting clinician).
Pregnant or planning on becoming pregnant.
Currently lactating.
Involved in another clinical trial (except observational trials) or expected to start one soon after completion.
Pre-existing oral disease or disability that would impair oral-administration or mucosal absorption.
Presence of known impairment of hepatic synthetic dysfunction.
Laboratory values suggestive of liver dysfunction.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Double-blind study. Allocation concealment achieved by:
1. Randomisation of participants using computer generated system that provides a code for participants
2. This code aligns with one of the two study medications (medicinal cannabis or placebo)
3. The study medications do not have any identifying information, and are only able to be differentiated by the code
4. De-coding information (i.e. which code corresponds with which product) is off site known only by industry partner producing the compound
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computerised sequence generation. Randomisation will be stratified for diagnosis, study site and treatment specifications.
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
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Data for sample size calculations were taken from Keefe et al 2014 (Cancer Chemotherapy and Pharmacology, PMID: 25055935), reporting the incidence of gut distress using the MDQ in people undergoing FOLFOX/FOLFIRI. Calculations were based on the incidence of gut distress and worst diarrhoea. Assuming an overall incidence of gut distress in the placebo group of 70% (combining reported incidences in Keefe et al for FOLFOX + FOLFIRI), a sample size of 176 participants gives 80% power, with two-sided alpha 0.05, to detect an absolute reduction of 21.7% in the incidence of gut distress (i.e. incidence in the CBD/THC group of 48.3%). Assuming a mean of 2 (worst diarrhoea) in the placebo group, and standard deviation of 1.5, a sample size of 176 participants gives 80% power, with two-sided alpha 0.05, to detect a reduction of 0.64 points (i.e. mean in the CBD/THC group of 1.36).

With this sample size, we are also sufficiently powered to detect changes in QoL (assessed using the EORTC-CLCQ30). Assumed means and standard deviations for the placebo group have been taken from the values reported for the FOLFOX group: the average of the 3 month and 6 month values was taken, along with the higher of the standard deviations (as this will provide conservative estimates).


Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/07/2022
Actual
Date of last participant enrolment
Anticipated
31/12/2024
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
176
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 21825 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 21826 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [3] 21827 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 36883 0
5000 - Adelaide
Recruitment postcode(s) [2] 36884 0
5011 - Woodville
Recruitment postcode(s) [3] 36885 0
5042 - Bedford Park

Funding & Sponsors
Funding source category [1] 310862 0
Government body
Name [1] 310862 0
Medical Research Future Fund (MRFF) - Australian Govern Department of Health
Country [1] 310862 0
Australia
Primary sponsor type
Government body
Name
Central Adelaide Local Health Network (CALHN)
Address
CALHN Research Services
Central Adelaide Local Health Network Inc. SA Health
Level 3, Roma Mitchell Building
136 North Terrace, Adelaide, SA 5000
Adelaide, South Australia
Country
Australia
Secondary sponsor category [1] 312119 0
None
Name [1] 312119 0
N/A
Address [1] 312119 0
N/A
Country [1] 312119 0
Other collaborator category [1] 282175 0
University
Name [1] 282175 0
The University of Adelaide
Address [1] 282175 0
North Terrace
Adelaide, 5000
South Australia
Country [1] 282175 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 310424 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 310424 0
Ethics committee country [1] 310424 0
Australia
Date submitted for ethics approval [1] 310424 0
25/02/2022
Approval date [1] 310424 0
Ethics approval number [1] 310424 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 117618 0
Dr Hannah Wardill
Address 117618 0
South Australian Health and Medical Research Institute (SAHMRI) - Level 5South
North Terrace
Adelaide
South Australia 5000
Country 117618 0
Australia
Phone 117618 0
+61 8 8128 4694
Fax 117618 0
Email 117618 0
[email protected]
Contact person for public queries
Name 117619 0
Hannah Wardill
Address 117619 0
South Australian Health and Medical Research Institute (SAHMRI) - Level 5South
North Terrace
Adelaide
South Australia 5000
Country 117619 0
Australia
Phone 117619 0
+61 8 8128 4694
Fax 117619 0
Email 117619 0
[email protected]
Contact person for scientific queries
Name 117620 0
Hannah Wardill
Address 117620 0
South Australian Health and Medical Research Institute (SAHMRI) - Level 5South
North Terrace
Adelaide
South Australia 5000
Country 117620 0
Australia
Phone 117620 0
+61 8 8128 4694
Fax 117620 0
Email 117620 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All study data (collected as part of the trial) underlying published results will be made available in appropriate data repositories. All data will be de-identified.
When will data be available (start and end dates)?
Immediately following publication (i.e. uploaded in parallel to publication) with no end date.
Available to whom?
Anyone who wishes to access it with a clear justification / purpose.
Available for what types of analyses?
Any purpose pending submission of appropriate proposal.
How or where can data be obtained?
Data will be accessible through an online data repository (determined based on journal requirements).


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.