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Trial registered on ANZCTR


Registration number
ACTRN12618001205224
Ethics application status
Approved
Date submitted
4/07/2018
Date registered
18/07/2018
Date last updated
26/06/2019
Date data sharing statement initially provided
26/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A study investigating safety, dosing and effectiveness of medicinal cannabis for symptom relief for patients with advanced cancer
Scientific title
An open label pilot study investigating safety, dosing and efficacy of cannabinoid medications for symptom relief in advanced cancer patients undergoing palliative care.
Secondary ID [1] 295412 0
NIL
Universal Trial Number (UTN)
NIL
Trial acronym
Medicinal Cannabinoids in Palliative Care (MedCan- Pilot)
Linked study record
NIL

Health condition
Health condition(s) or problem(s) studied:
Cancer 308644 0
Fatigue 308645 0
Pain 308646 0
Nausea 308647 0
Shortness of Breath 308648 0
Psychological effects 308649 0
Condition category
Condition code
Cancer 307589 307589 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study is a prospective, two-arm, open label trial of escalating doses of Cannabidiol (CBD) and Delta-9-Tetrahydrocannabinol (THC). The choice of the study drug will be at the discretion of the patient, doctor and dependent on supply. Each patient will follow a dose titration schedule for 14 days and a follow on stable dose for a further 14 days.
Concentration of medication:
Arm 1: CBD (Cannabidiol 100mg/ml) oral oily liquid
Arm 2: THC (Delta-9-Tetrahydrocannabinol 10mg/ml) oral oily liquid

Dosing schedule
Dose titration (days 0 – 14) will be confirmed by the treating doctor with doses starting at:
Arm 1
Days 0 & 1 – 1 dose/day = total daily dose 50mg (0.5ml)
Day 2 & 3 – 1 dose/day = total daily dose 100mg (1ml)
Day 4 & 5 – 2 dose/day = total daily dose 200mg (2ml)
Day 6 & 7 – 3 doses/day = total daily dose 300mg (3ml)
Day 8 & 9 – 3 doses/day = total daily dose 400mg (4ml)
Day 10 & 11 – 3 doses/day = total daily dose 500mg (5ml)
Day 12 & 13 – 3 doses/day = total daily dose 600mg (6ml)
Day 14 – 28 – Continue on final dose reached

Arm 2
Days 0 & 1 – 1 dose/day = total daily dose 2.5mg (0.25ml)
Day 2 & 3 – 1 dose/day = total daily dose 5mg (0.5ml)
Day 4 & 5 – 2 dose/day = total daily dose 10mg (1ml)
Day 6 & 7 – 3 doses/day = total daily dose 15mg (1.5ml)
Day 8 & 9 – 3 doses/day = total daily dose 20mg (2ml)
Day 10 & 11 – 3 doses/day = total daily dose 25mg (2.5ml)
Day 12 & 13 – 3 doses/day = total daily dose 30mg (3ml)
Day 14 – 28 – Continue on final dose reached

Each patient will be advised to increase their dose according to the dosing schedule until they are satisfied with their symptom improvement and there are no unacceptable side effects (according to CTCAE graded >4). The patient then will be given the option of remaining on the cannabinoid preparation for continuing assessment of efficacy and adverse events for a total of 28days.
Patients will have the choice of lowering their dose according to symptom improvement. Dose titration downwards will be in consultation with the doctor.
Intervention code [1] 301726 0
Treatment: Drugs
Comparator / control treatment
CBD (Cannabidiol 100mg/ml) oral oily liquid
Control group
Active

Outcomes
Primary outcome [1] 306574 0
Change from baseline of total composite ESAS TSDS
Timepoint [1] 306574 0
Assessed at baseline and that at days 7 and 14. The primary endpoint is day 14 compared to baseline.
Secondary outcome [1] 348918 0
Patient-determined effective doses of different cannabis products, defined as the dose that achieves symptom relief with acceptable side-effects
Timepoint [1] 348918 0
Assessed at days 2, 4, 7, 9, 11, 14, 16, 18, 21, 23, 25 and day 28.
Secondary outcome [2] 348921 0
Global Impression of Change Score
Timepoint [2] 348921 0
Assessed at baseline and compared at days 7, 14, 21 and 28
Secondary outcome [3] 348922 0
DASS-21 score assessing depression, anxiety and stress
Timepoint [3] 348922 0
Assessed at baseline and compared at days 7, 14, 21 and 28
Secondary outcome [4] 349191 0
Quality of Life using questionnaire EORTC QLQ-C15 PAL
Timepoint [4] 349191 0
Assessed at baseline and compared at days 14 and 28
Secondary outcome [5] 349194 0
Adverse Events (AE) recorded using Common Terminology Criteria for Adverse Events v4.0 (CTCAE v4.0) All AE's will be recorded at baseline until end of study (day 28).Particular attention will be given to: confusion, somnolence, personality change, paranoia, anxiety, mood change, psychosis, hypertension, tachycardia, sweating, nausea, vomiting, abdominal pain
Timepoint [5] 349194 0
Assessed at baseline and compared at days 2, 4, 7, 9, 11, 14, 16, 18, 21, 23, 25 and day 28
Secondary outcome [6] 349196 0
Combined feasibility: number of participants screened, screen fails and completing 14 days, number completing 28 days. Data will be collected from patients health records and clinical notes
Timepoint [6] 349196 0
Once recruitment of sample size reached.

Eligibility
Key inclusion criteria
Patients with advanced histologically proven cancer (metastatic or locally advanced solid tumours or advanced haematological malignancies) who have been referred or known to the palliative care team who:
- have an ESAS TSDS >10
- at lease one individual ESAS score >3
- AKPS score >30
- aged >25yrs. English speaking (or interpreted available), give fully informed consent
- have a negative pregnancy urine test at eligibility (only if of reproductive potential) and agree to avoid pregnancy during the study and 12
weeks following the last dose of the study drug. Males must agree to avoid fathering a child and to not donate sperm during the study and
for at least 12 weeks following the last dose of the study drug
- able to tolerate oral medication and comply with trial requirements
- agree to use no other cannabis based product
- understand it is illegal to drive a motor vehicle
Minimum age
25 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with:
- a history of hypersensitivity to any cannabinoid product
- unstable untreated cardiovascular disease (hypertension, ischemic heart disease, congestive cardiac failure)
- severe hepatic impairment (total bilirubin >1.5 times the upper limit of the institution's normal range. Asparate aminotransferase (AST), and Alanine
aminotransferase (ALT) >3.0 time the upper limit. Subjects with liver metastasis may have an AST and ALT >5.0 time the upper limit
- severe renal impairment (eGFR <20mls/min/1.73m2)
- history of psychiatric disorders (severe depression or anxiety, personality disorder, psychosis, schizophrenia, first degree relative with schizophrenia
and/or suicidal ideation)
- cognitive impairment (SLUMS - St Louis University Mental Status) examination <20/30; known substance use disorder (ASSIST - Alcohol, Smoking and
Substance Involvement Screening Test) examination score <27+; historyof drug diversion may be a risk for them or their family/carers
- females who are pregnant or lactating
- participation in a trial of a new clinical entity with the last 28 days
- treatment with a new specific anticancer agent (chemotherapy, targeted or hormonal therapy) within the last 21 days or radioation within the last 7 days

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Each participant will complete a 28 day period of treatment. They will receive either Arm 1 or Arm 2
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Analysis will compose of assessing composite scores, rather than individual scores we have elected to use an improvement of >6 in the TSDS as the primary outcome measure. Descriptive analyses and frequency distributions will be generated from participants’ demographic and clinical characteristics, with all variables explored using graphical methods and summary statistics. Similarly, analysis of primary and secondary outcome will be descriptive only.
The aim is to recruit 5 participants in each arm (at day 14 – time of primary outcome) across a 12 month recruitment period in order to obtain sufficient pilot data to inform subsequent controlled trials. The sample size if currently restricted by the limited availability of approved products.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
22/10/2018
Actual
15/10/2018
Date of last participant enrolment
Anticipated
Actual
2/01/2019
Date of last data collection
Anticipated
31/10/2019
Actual
4/02/2019
Sample size
Target
15
Accrual to date
Final
21
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 11307 0
Mater Adult Hospital - South Brisbane
Recruitment hospital [2] 11308 0
Mater Private Hospital - South Brisbane
Recruitment postcode(s) [1] 23206 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 299999 0
Government body
Name [1] 299999 0
National Health and Medical Research Council (NHMRC)/Medical Research Future Fund (MRFF)
Country [1] 299999 0
Australia
Primary sponsor type
University
Name
The University Of Queensland
Address
The University of Queensland
Cumbrae-Stewart Building
Research Road
Brisbane Qld 4072
Country
Australia
Secondary sponsor category [1] 299383 0
Hospital
Name [1] 299383 0
Mater Misericordiae Limited
Address [1] 299383 0
Mater Misericordiae Ltd
Raymond Terrace
South Brisbane Qld 4101
Country [1] 299383 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300854 0
Mater Misericordiae Ltd Human Research Ethics Committee (MML HREC)
Ethics committee address [1] 300854 0
Ethics committee country [1] 300854 0
Australia
Date submitted for ethics approval [1] 300854 0
04/06/2018
Approval date [1] 300854 0
28/06/2018
Ethics approval number [1] 300854 0
HREC/18/MHS/83

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

Contacts
Principal investigator
Name 85042 0
Prof Janet Hardy
Address 85042 0
Medical Director Mater Cancer Care Centre
Director Palliative and Supportive Care Services
Mater Misericordiae Ltd
Raymond Terrace
South Brisbane, Qld 4101
Country 85042 0
Australia
Phone 85042 0
+61 7 3163 2775
Fax 85042 0
+61 7 3163 2701
Email 85042 0
Janet.Hardy@mater.org.au
Contact person for public queries
Name 85043 0
Georgie Cupples
Address 85043 0
Clinical Trial Coordinator
Palliative and Supportive Care
Mater Misericordiae Ltd
Raymond Terrace
South Brisbane, Qld 4101
Country 85043 0
Australia
Phone 85043 0
+61 7 3163 6057
Fax 85043 0
+61 7 3163 1588
Email 85043 0
Georgie.Cupples@mater.org.au
Contact person for scientific queries
Name 85044 0
Janet Hardy
Address 85044 0
Medical Director Mater Cancer Care Centre
Director Palliative and Supportive Care Services
Mater Misericordiae Ltd
Raymond Terrace
South Brisbane, Qld 4101
Country 85044 0
Australia
Phone 85044 0
+61 7 3163 2775
Fax 85044 0
+61 7 3163 2701
Email 85044 0
Janet.Hardy@mater.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data being reviewed at this time


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
SourceTitleYear of PublicationDOI
EmbaseAn open-label pilot study testing the feasibility of assessing total symptom burden in trials of cannabinoid medications in palliative care.2020https://dx.doi.org/10.1089/jpm.2019.0540
N.B. These documents automatically identified may not have been verified by the study sponsor.