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Trial registered on ANZCTR


Registration number
ACTRN12619000491167
Ethics application status
Approved
Date submitted
5/03/2019
Date registered
26/03/2019
Date last updated
26/03/2019
Date data sharing statement initially provided
26/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Tetrahydrocannabinol for cancer-related anorexia
Scientific title
Phase IIb double-blind, placebo-controlled study of oral delta-9-tetrahydrocannabinol (Namisol®) for anorexia in people with advanced cancer
Secondary ID [1] 294792 0
PaCCSC 031/18
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer-related anorexia 307721 0
Condition category
Condition code
Cancer 306775 306775 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Namisol®, (Echo Pharmaceuticals BV, Netherlands), an oral tablet containing delta 9 tetrahydrocannabinol. Dose titration will occur day 1 – 7, with all doses taken 60 minutes before meals. Participants will receive oral Namisol® 1.5 mg at night before dinner on day one, titrated up to 4.5 mg three times a day (1.5mg twice a day on day 2, 3mg twice a day on day 3, 3mg three times a day day 4 and 5, 4.5mg three times a day on day 6 and 7). There will be allowance for dose reduction to the prior dose level or the timing can be changed to after food if intolerable adverse effects are experienced (these changes due to tolerability are carried to maintenance phase). The maintenance phase (7 days) will be from day 8-14 with Namisol® 4.5 mg three times a day before meals (or lower dose or after meals if required). The primary outcome will be measured on day 14. Participants without toxicity will then enter the two-week extension phase (day 15-28) continuing on the dose as per maintenance phase, with weekly assessments for efficacy and toxicity. At the end of the study participants who will not continue on THC treatment, will have a weaning phase (4.5mg BD for 2 days, followed by 4.5 mg before dinner, then 3mg before dinner and 1.5mg before dinner respectively for the next three days). Continuation on THC treatment after extension phase will be off study and monitoring will be according to clinician direction.
Intervention code [1] 301107 0
Treatment: Drugs
Comparator / control treatment
Oral placebo Namisol® (Echo Pharmaceuticals BV, Netherlands) containing identical ingredients except the active ingredient THC, titrated three times a day 60 minutes before meals (matched to 1.5 mg tablet size).
Control group
Placebo

Outcomes
Primary outcome [1] 305767 0
Anorexia-related symptoms and concerns as measured by the 12-item Functional Assessment of anorexia cachexia therapy (FAACT) anorexia cachexia sub-scale
Timepoint [1] 305767 0
Baseline, Days 2, 3, 5, Day 7, Day 14 (primary timepoint), Day 21, Day 28.
Secondary outcome [1] 346419 0
Pre-meal Numerical Rating Scale (NRS) for appetite (0 = no appetite to 10 = best possible appetite)).
Timepoint [1] 346419 0
From baseline, one hour after each dose day 1 – 28
Secondary outcome [2] 346420 0
Taste and smell alteration assessed as a composite outcome by the Taste and Smell Survey
Timepoint [2] 346420 0
Baseline, Day 7, Day, 14, Day 21, Day 28
Secondary outcome [3] 346421 0
GAD-7 (anxiety symptoms)
Timepoint [3] 346421 0
Baseline, Day 7, Day, 14, Day 21, Day 28
Secondary outcome [4] 346422 0
Treatment Satisfaction Questionnaire for Medication
Timepoint [4] 346422 0
Day 7, Day, 14, Day 21, Day 28
Secondary outcome [5] 346423 0
Patient Global impression of change
Timepoint [5] 346423 0
Day 7, Day, 14, Day 21, Day 28
Secondary outcome [6] 346424 0
Functional Assessment of Anorexia/Cachexia
Therapy (FAACT) questionnaire - symptom items (nausea, pain, vomiting, sleep, fatigue)
Timepoint [6] 346424 0
Baseline, Days 2, 3, 5, Day 7, Day 14, Day 21, Day 28.
Secondary outcome [7] 346425 0
Brief Pain Inventory (short form)
Timepoint [7] 346425 0
Baseline, Day 7, Day, 14, Day 21, Day 28
Secondary outcome [8] 346426 0
Quality of Life (FAACT total score)
Timepoint [8] 346426 0
Baseline, Days 2, 3, 5, Day 7, Day 14, Day 21, Day 28.
Secondary outcome [9] 346427 0
Body Mass Index (study specific questionnaire and digital scale)
Timepoint [9] 346427 0
Baseline, Day 7, Day, 14, Day 21, Day 28
Secondary outcome [10] 346428 0
Food diary (time of meal relative to the study intervention dose, type of food, amount (weight in grams or volume in millitres)
Timepoint [10] 346428 0
Daily until Day 14
Secondary outcome [11] 346429 0
Numerical rating scale of adverse effects (for example intoxication, hallucinations, dizziness, nausea, anxiety, drowsiness)
Timepoint [11] 346429 0
Once a day at the same time each evening, Day 1-28
Secondary outcome [12] 346430 0
NCI common terminology for adverse events V4.03
Timepoint [12] 346430 0
Baseline, day 3, 5, 7, 14, 21, 28
Secondary outcome [13] 346431 0
Number of inpatient admissions by Diagnostic Related Group (DRG) assessed from medical record
Timepoint [13] 346431 0
As recorded
Secondary outcome [14] 346432 0
Dietician assessment (composite of number and duration) assessed from medical record
Timepoint [14] 346432 0
assessed weekly for study duration
Secondary outcome [15] 367984 0
PHQ-9 (depression symptoms)
Timepoint [15] 367984 0
Baseline, Day 7, Day, 14, Day 21, Day 28
Secondary outcome [16] 368672 0
Days spent in hospital assessed from medical record
Timepoint [16] 368672 0
as recorded

Eligibility
Key inclusion criteria
• Age greater than or equal to 18 years;
• Advanced cancer;
• Anorexia for at least 2 weeks (defined as numeric rating scale [0 no appetite – 10 best possible appetite] score greater than or equal to 4) unresponsive to the optimisation of treatment of causative medical conditions
• English-speaking (or have an interpreter available);
• Written informed consent.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Inability to take medications orally
• Severe hepatic impairment (defined as bilirubin greater than or equal to 3 times upper limit of normal; aspartate transaminase and/or alanine transaminase > 5 times upper limit of normal) clinically determined to be due to hepatic impairment
• Renal impairment (estimated glomerular filtration rate of <10 mL/min)
• Cognitive impairment (Montreal Cognitive Assessment (MOCA score<26);
• Psychiatric disorders (severe depression or anxiety, personality disorder, history of psychosis, schizophrenia, and/or suicidal ideation);
• Acute delirium or delirium within < 30 days;
• Unstable cardiovascular disease (uncontrolled hypertension, unstable ischaemic heart disease, unstable congestive cardiac failure);
• Prior adverse reaction to botanical cannabis/pharmaceuticals containing cannabinoids;
• Pregnant, breastfeeding or unwillingness to use oral contraceptives;
• Substance use disorder (DSM 5 criteria; to alcohol, opioids, benzodiazepines or simulants (excluding caffeine, tobacco).
• Recent use of cannabis or cannabinoids within < 30 days (based on self-report and urine drug screen at eligibility).
• Prescribed opioid, benzodiazepine, antidepressant, antipsychotic, corticosteroid, progestin, omega fatty acids and/or dietary supplements, which do not meet the therapies allowed at eligibility assessment
• Current participation in a clinical trial of another chemical entity.


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)
The site clinical trial pharmacist will dispense the study medication as a blister package for each week of the study from the appropriate stock of study medication (Namisol 1.5 mg, placebo) according to the randomisation schedule and labelled with the pre-determined allocation code.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The REDCap randomisation tool will be used to facilitate randomisation. Random allocation tables will be created and uploaded into the REDCap project. Treatment for each participant will be allocated according to a block randomisation schedule in a 1:1 ratio. Block randomisation will ensure even allocation to each code. There will be no stratification at the randomisation level for this study.
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)
Efficacy
Statistical methods / analysis
Intention-to-treat analysis will be used for all statistical comparisons. For each treatment group and overall, the demographic data will be summarised as mean, standard deviation, minimum, median, and maximum for continuous variables, and as frequencies and percentages for categorical variables. Questionnaires that provide continuous responses will be summarised as described above with the addition of the 95% CI for the mean if appropriate. Questionnaires that provide categorical responses will be summarised as frequencies and percentages with the addition of 95% CI for the mean if appropriate.

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)
NSW
Recruitment hospital [1] 10845 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [2] 10846 0
Concord Repatriation Hospital - Concord
Recruitment hospital [3] 10847 0
Greenwich Hospital - Greenwich
Recruitment hospital [4] 10848 0
Bankstown-Lidcombe Hospital - Bankstown
Recruitment hospital [5] 10849 0
Liverpool Hospital - Liverpool
Recruitment hospital [6] 13270 0
Calvary Health Care Sydney Ltd - Kogarah
Recruitment hospital [7] 13271 0
St George Hospital - Kogarah
Recruitment hospital [8] 13287 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [9] 13288 0
Braeside Hospital - Prairiewood
Recruitment postcode(s) [1] 25858 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 22591 0
2065 - Greenwich
Recruitment postcode(s) [3] 22590 0
2139 - Concord
Recruitment postcode(s) [4] 22593 0
2170 - Liverpool
Recruitment postcode(s) [5] 25859 0
2176 - Prairiewood
Recruitment postcode(s) [6] 22592 0
2200 - Bankstown
Recruitment postcode(s) [7] 25835 0
2217 - Kogarah
Recruitment postcode(s) [8] 22589 0
2560 - Campbelltown

Funding & Sponsors
Funding source category [1] 299399 0
Government body
Name [1] 299399 0
NSW Health
Address [1] 299399 0
3 Miller Street
North Sydney NSW 2060
Australia
Country [1] 299399 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Palliative Care Clinical Studies Collaborative
Address
Level 3, 235 Jones St Ultimo NSW 2007
PO Box 123 Broadway NSW 2007 Australia
Country
Australia
Secondary sponsor category [1] 298685 0
None
Name [1] 298685 0
Address [1] 298685 0
Country [1] 298685 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300302 0
South Western Sydney Local Health District Human Research Ethics Committee.
Ethics committee address [1] 300302 0
Locked Bag 7103, LIVERPOOL BC NSW 1871
Ethics committee country [1] 300302 0
Australia
Date submitted for ethics approval [1] 300302 0
28/03/2018
Approval date [1] 300302 0
18/05/2018
Ethics approval number [1] 300302 0

Summary
Brief summary
The purpose of this study is to evaluate if tetrahydrocannabinol (THC) can improve anorexia in people with cancer.

Who is it for?
You may be eligible for this study if you are aged 18 or over, have advanced cancer, and have experienced reduced appetite (anorexia) for at least 2 weeks

Study details
Participants will be randomised by chance into two groups. Both groups will take an increasing dose of oral tablets before meals for one week before sustaining the high dose for up to 3 weeks. In one group, the tablets will contain THC and in the other group the tablets will be the same except not contain any THC. All participants in this study will complete a series of questionnaires and complete a food diary.

It is hoped this research will provide some evidence about the utility of THC for appetite improvement in this population
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 83214 0
Prof Meera Agar
Address 83214 0
Ingham Institute of Applied Medical Research
1 Campbell Street, Liverpool NSW 2170
Country 83214 0
Australia
Phone 83214 0
+61 2 9514 4243
Fax 83214 0
Email 83214 0
meera.agar@health.nsw.gov.au
Contact person for public queries
Name 83215 0
Prof Meera Agar
Address 83215 0
Ingham Institute of Applied Medical Research
1 Campbell Street, Liverpool NSW 2170
Country 83215 0
Australia
Phone 83215 0
+61 2 9514 4243
Fax 83215 0
Email 83215 0
meera.agar@health.nsw.gov.au
Contact person for scientific queries
Name 83216 0
Prof Meera Agar
Address 83216 0
Ingham Institute of Applied Medical Research
1 Campbell Street, Liverpool NSW 2170
Country 83216 0
Australia
Phone 83216 0
+61 2 9514 4243
Fax 83216 0
Email 83216 0
meera.agar@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
requires specific approval from funding body
What supporting documents are/will be available?
Study protocol
Informed consent form
Ethical approval
Summary results
No Results