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Trial registered on ANZCTR


Registration number
ACTRN12619001534178p
Ethics application status
Submitted, not yet approved
Date submitted
30/09/2019
Date registered
6/11/2019
Date last updated
6/11/2019
Date data sharing statement initially provided
6/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A phase I/II double-blind, randomised controlled trial assessing effect of medicinal cannabis on quality of life and symptom control in advanced cancer.
Scientific title
A phase I/II double-blind, randomised controlled trial assessing effect of medicinal cannabis on quality of life and symptom control in advanced cancer.
Secondary ID [1] 299454 0
None
Universal Trial Number (UTN)
U1111-1241-2539
Trial acronym
RESONANCE
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Advanced Cancer 314661 0
Palliative Care 314662 0
Condition category
Condition code
Cancer 312993 312993 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a combined Phase 1/2 study. Phase 1 is confirmation of dose finding and participation will last up to 56 days (up to 28 days screening and 28 days of investigational product administration). Phase 2 is addressing the primary endpoint and will last up to 196 days (up to 28 days screening and 168 days of investigational product). The Investigational Product is CGL002 (Medicinal Cannabis) or Placebo, between 2.5mg and 30mg administered one to three times a day, oral liquid administered via syringe, daily for a maximum of 168 days/6 months. The dose is commenced at 2.5mg/once a day and up-titrated daily based on symptom control and tolerance to a maximum daily dose of 30mg. Participants increase their dose by 2.5mg at each interval (e.g. morning/afternoon/evening) for symptom control. This is based on their own tolerability of the IP.



Intervention code [1] 315697 0
Treatment: Drugs
Comparator / control treatment
Placebo, oral liquid, administered one to three times a day, daily for a maximum of 184 days/6 months. The placebo will be composed of a medium-chain triglyceride (MCT) oil.

Control group
Placebo

Outcomes
Primary outcome [1] 321563 0
Phase 1 Primary Outcome (composite):
To determine the safety, tolerability, and dose range of the study drug by evaluating and characterising the pharmacokinetic profile of medicinal cannabis and active metabolites, analysis of dose-limiting toxicities, and adverse events.
Pharmacokinetic parameters being assessed include serum concentration of CBD002 and metabolites.
Dose-limiting toxicities and adverse events will be measured by CTCAE criteria which can be classified by clinical examination, laboratory findings or patient reported symptoms.
Timepoint [1] 321563 0
Baseline (pre-dose), and 1, 2, 4, and 8 hours post administration of study drug, done on Days 1, 8, 15, and 29 post initiation of Medicinal Cannabis/Placebo.
Primary outcome [2] 321564 0
Phase 2 Primary Outcome:
To determine the impact of medicinal cannabis on global quality of life, as measured by change in EORTC QLQ PAL-Q30 from baseline.
Timepoint [2] 321564 0
Day 29 post initiation of Medicinal Cannabis/Placebo.
Secondary outcome [1] 375358 0
Phase 1 Secondary Outcomes:
To test the feasibility of the objectives proposed in the Phase 2 study. This includes the impact of medicinal cannabis on global quality of life, pain, insomnia, nausea, anxiety and treatment satisfaction (please review secondary outcomes below for specifics of method of outcome assessment). Feasibility of the objectives will be assessed by
o Questionnaires understandable and acceptable to all participants
o The IP dosing uptitration schedule able to be followed by all participants
o Feasibility of self-administration of the IP

Timepoint [1] 375358 0
Day 29 post initiation of Medicinal Cannabis or Placebo.
Secondary outcome [2] 375359 0
Phase 2 Secondary Outcomes:
To determine impact of medicinal cannabis on global quality of life, as measured by EORTC QLQ PAL-Q30.
Timepoint [2] 375359 0
At Days 56, 84, 112, 140 and 168 post initiation of Medicinal Cannabis/Placebo.
Secondary outcome [3] 375660 0
Phase 1 Secondary Outcome:
To undertake exploratory pharmacokinetics studies profiling the medicinal cannabis and active metabolites. Pharmacokinetic parameters being assessed include serum concentration of CBD002 and metabolites.
Timepoint [3] 375660 0
Day 29 post initiation of Medicinal Cannabis or Placebo.
Secondary outcome [4] 375661 0
Phase 2 Secondary Outcome:
To evaluate impact of medicinal cannabis on:
1) Pain (as measured by change in BPI-SF (Brief Pain Inventory – Short Form)),



Timepoint [4] 375661 0
At Days 56, 84, 112, 140 and 168 post initiation of Medicinal Cannabis/Placebo.
Secondary outcome [5] 375662 0
Phase 2 Secondary Outcome:
To evaluate impact of medicinal cannabis on:
2) Anorexia (as measured by FAACT (Functional Assessment of Anorexia/Cachexia and weight)),
Timepoint [5] 375662 0
At Days 56, 84, 112, 140 and 168 post initiation of Medicinal Cannabis/Placebo.
Secondary outcome [6] 375663 0
Phase 2 Secondary Outcome:
*To evaluate impact of medicinal cannabis on:
3) Anxiety (as measured by HADS (Hospital Anxiety and Depression Scale)),
Timepoint [6] 375663 0
At Days 56, 84, 112, 140 and 168 post initiation of Medicinal Cannabis/Placebo.
Secondary outcome [7] 375664 0
Phase 2 Secondary Outcome:
*To evaluate impact of medicinal cannabis on:
4) Sleep (as measured by ISI (Insomnia Severity Index)),
Timepoint [7] 375664 0
At Days 56, 84, 112, 140 and 168 post initiation of Medicinal Cannabis/Placebo.
Secondary outcome [8] 375665 0
Phase 2 Secondary Outcome:
*To evaluate impact of medicinal cannabis on:
5) Nausea as measured by a NRS (Numerical Rating Scale))
Timepoint [8] 375665 0
At Days 56, 84, 112, 140 and 168 post initiation of Medicinal Cannabis/Placebo.
Secondary outcome [9] 375666 0
Phase 2:
To evaluate treatment satisfaction as measured by (TSQM) Treatment Satisfaction Questionnaire for Medication
Timepoint [9] 375666 0
At Days 56, 84, 112, 140 and 168 post initiation of Medicinal Cannabis/Placebo.
Secondary outcome [10] 375667 0
Phase 2:
*To evaluate caregiver burden as measured by QOL (CQOL-C)
Timepoint [10] 375667 0
At Days 56, 84, 112, 140 and 168 post initiation of Medicinal Cannabis/Placebo.
Secondary outcome [11] 375668 0
To determine the safety and optimal Phase 2 dose range of medicinal cannabis as measured by occurrence of DLTs and adverse events, clinically meaningful changes from baseline in clinical laboratory parameters. DLTs and adverse events will be assessed by standard CCTAE Criteria.
This is a composite outcome.
Timepoint [11] 375668 0
At Days 56, 84, 112, 140 and 168 post initiation of Medicinal Cannabis/Placebo.

Eligibility
Key inclusion criteria
*Able to provide written informed consent and greater than or equal to 18 years of age.
*Willing and able to comply with all study requirements, including treatment, blood sampling and other assessments.
*Patients with incurable advanced cancer, of any histological subtype.
*Measurable disease based on RECIST 1.1 criteria.
*Life expectancy greater than 2 months.
*Female patients of childbearing potential should have a negative pregnancy test within 72 hours prior to receiving the first dose of study medication and use a medically acceptable form of contraception.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
*Patients with recent change to systemic anticancer treatment (chemotherapy, immunotherapy, targeted therapy, hormonal therapy) on first day of study:

1. Patients with recent change to systemic anticancer treatment (chemotherapy, immunotherapy, targeted therapy, hormonal therapy) on first day of study:
• Commenced new anticancer treatment within the last 60 days
• Completed anticancer treatment <14 days ago
• Planning to receive new anticancer treatment in the next 30 days
2. Having current radiotherapy or planning to have radiotherapy in the next 30 days
3. Severe hepatic impairment, as defined by:
• aspartate aminotransferase (AST) >5 times upper limit of normal, or
• alanine aminotransferase (ALT) >5 times upper limit of normal
4. Conditions preventing adequate absorption of study drug (including difficulty swallowing medications, intestinal obstruction, inflammatory bowel condition, colitis)
5. Inadequate renal function, defined as eGFR <30ml/min (using CKD-EPI calculation)
6. Substance use disorder (ICD-10 criteria (abuse, dependence) to alcohol, opioids, benzodiazepines, or illicit stimulants
7. Current or recent use of cannabis within 30 days prior to study entry. Participants must return a negative drugs of abuse urine test.
8. Prior clinically significant adverse reaction to cannabis or cannabinoid based medications.
9. Unwilling to avoid driving or operating machinery whilst on trial.
10. Prior hypersensitivity or intolerable adverse reaction to cannabis or cannabinoid based medications. Patients on strong CYP3A4 inducers or inhibitors, or on strong CYP2C19 inducers or inhibitors (refer to Appendix 3).
11. Psychiatric or neurodegenerative condition which in the opinion of the investigator may compromise patient safety.
12. Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a highly effective and reliable means of contraception. Male participants must have been surgically sterilised or use a (double if required) barrier method of contraception.
13. Actively receiving a concurrent investigational product.

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)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
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
Participants are blinded to their treatment for the duration of the trial.
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet 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)
VIC
Recruitment hospital [1] 14917 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 14918 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [3] 14919 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [4] 14920 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 28186 0
3084 - Heidelberg
Recruitment postcode(s) [2] 28187 0
3050 - Parkville
Recruitment postcode(s) [3] 28188 0
3000 - Melbourne
Recruitment postcode(s) [4] 28189 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 303955 0
Government body
Name [1] 303955 0
Victorian Cancer Agency
Address [1] 303955 0
50 Lonsdale Street
Melbourne, Victoria, Australia
3000
Country [1] 303955 0
Australia
Primary sponsor type
Other
Name
Olivia Newton-John Cancer Research Institute
Address
Level 5, ONJWRC , Austin Health
145 Studley Road
Heidelberg VIC 3065
Country
Australia
Secondary sponsor category [1] 304121 0
None
Name [1] 304121 0
Address [1] 304121 0
Country [1] 304121 0
Other collaborator category [1] 280981 0
Commercial sector/Industry
Name [1] 280981 0
Cann Group Limited
Address [1] 280981 0
4 Research Avenue, Bundoora,
Victoria 3083 Australia
Country [1] 280981 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 304455 0
Austin Health HREC
Ethics committee address [1] 304455 0
145 Studley Road
Heidleberg Victoria 3084
Ethics committee country [1] 304455 0
Australia
Date submitted for ethics approval [1] 304455 0
30/10/2019
Approval date [1] 304455 0
Ethics approval number [1] 304455 0

Summary
Brief summary
The purpose of this study is to see if a trial of the impact of medicinal cannabis on quality of life and symptoms in people with advanced cancer is feasible/possible.

Who is it for?
You may be eligible fo this study if you are aged 18 or over, have advanced cancer and a life expectancy of at least 2 months.

Study details
All participants in this study will receive medicinal cannabis by mouth, begining once a day for and increasing to up to 3 times a day, until their symptom control is adequate, for a period of 6 months. All participants will provide blood samples, scans and answer questionnaires. We would also like your carer to be involved, if you have one.

It is hoped this preliminary study will demonstrate a full-scale trial is possible, indicate the appropriate dose/s to use in a full-scale trial, and provide useful information how cannabis is metabolised by the body.
Trial website
Trial related presentations / publications
None
Public notes
None

Contacts
Principal investigator
Name 97006 0
Dr Aaron Wong
Address 97006 0
Palliative Care
Austin Health
145 Studley Road
Heidelberg VIC 3084
Country 97006 0
Australia
Phone 97006 0
+61 3 9496 5000
Fax 97006 0
Email 97006 0
trials@onjcri.org.au
Contact person for public queries
Name 97007 0
Dr Jodie Palmer
Address 97007 0
Olivia Newton-John Cancer Research Institute
Level 5, ONJWRC
145 Studley Road
Heidelberg VIC 3084
Country 97007 0
Australia
Phone 97007 0
+61 3 9496 5000
Fax 97007 0
Email 97007 0
trials@onjcri.org.au
Contact person for scientific queries
Name 97008 0
Dr Jodie Palmer
Address 97008 0
Olivia Newton-John Cancer Research Institute
Level 5, ONJWRC
145 Studley Road
Heidelberg VIC 3084
Country 97008 0
Australia
Phone 97008 0
+61 3 9496 3573
Fax 97008 0
Email 97008 0
trials@onjcri.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 will be pooled and presented as such.
What supporting documents are/will be available?
Study protocol
Informed consent form
Ethical approval
How or where can supporting documents be obtained?
Type [1] 5167 0
Study protocol
Citation [1] 5167 0
Link [1] 5167 0
Email [1] 5167 0
trials@onjcri.org.au
Other [1] 5167 0
Contact ONJCRI directly
Attachment [1] 5167 0
Type [2] 5168 0
Informed consent form
Citation [2] 5168 0
Link [2] 5168 0
Email [2] 5168 0
trials@onjcri.org.au
Other [2] 5168 0
Contact ONJCRI directly
Attachment [2] 5168 0
Type [3] 5169 0
Ethical approval
Citation [3] 5169 0
Link [3] 5169 0
Email [3] 5169 0
trials@onjcri.org.au
Other [3] 5169 0
Contact ONJCRI directly
Attachment [3] 5169 0
Summary results
No Results