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Trial registered on ANZCTR


Registration number
ACTRN12615000414516
Ethics application status
Not yet submitted
Date submitted
20/04/2015
Date registered
1/05/2015
Date last updated
26/02/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
An evaluative study on the safety and efficacy of standard anti-emetics compared to standard anti-emetics plus natural cannabinoids extract for the treatment of chemotherapy induced nausea and vomiting
Scientific title
A Phase IIa Randomised Placebo Controlled Adjunctive Antiemetic Therapy With a Cannabinoid Extract in Preventing Chemotherapy-Induced Nausea and Vomiting in Patients With Cancer Receiving Moderately to Highly Emetogenic Chemotherapy
Secondary ID [1] 286567 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Emetogenicity
294819 0
Chemotherapy induced nausea and vomiting 294820 0
Cancer 294821 0
Condition category
Condition code
Cancer 295093 295093 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The clinical study will investigate the efficacy and safety of a nasal spray delivered whole plant derived cannabinoid (CBD) extract. The patient will be instructed to initially administer 5 mg of CBD active ingredient, per spray per nostril, prior to commencing chemotherapy providing a total dose of 10 mg. Administration of additional sprays will be a maximum of 6 sprays per nostril over the next 24 hours for a total of 70 mg/day on chemotherapy day and 60 mg/day (6 sprays per nostril) on days 1– 4.

Schedule Dose: Day 0 / Chemotherapy Day: Administer 1 nasal spray per nostril prior to commencement of chemotherapy and thereafter 1 nasal spray per nostril every 4 hours [maximum day 0 dose is 70 mg]
Schedule Dose: Days 1–4: Administer 1 nasal spray per nostril every 4 hours [maximum day 1–4 dose 60 mg / day]
Total Dose to be administered over one chemotherapy cycle is 310 mg of Whole Plant CBD ‘Rich’ Extract

Duration: Up to a maximum of 3 chemotherapy cycles
Methods and tools used to monitor adherence and capture information for endpoints: 1) Rhodes Inventory of Nausea, Vomiting and Retching (RINV) 2) The Functional Living Index-Emesis-5 Day Recall (FLIE-5DR) 3) Edmonton Symptom Assessment Scale (ESAS) 4) Patient Generated-Subjective Global Assessment (PG-SGA) 5) Functional Assessment of Cancer Therapy-General (FACT-G) and Fatigue (Facit-F) subscale 6) Treatment Adherence Questionnaire/Table
Intervention code [1] 291674 0
Prevention
Intervention code [2] 291675 0
Treatment: Drugs
Comparator / control treatment
The comparator will be delivered in an identical format i.e., as an intranasal spray. It will contain a low dose Vitamin E as the comparator control (5 mg Vitamin E per spray per nostril administered every 4 hours as per the schedule
Control group
Placebo

Outcomes
Primary outcome [1] 294853 0
To evaluate the overall efficacy of standard anti-emetics compared to standard anti-emetics plus natural cannabinoids extract for the treatment of CINV. Efficacy will be measured by the proportion of patients that achieve a ‘complete response’, where ‘complete response’ is defined as no vomiting and no use of rescue medication
Timepoint [1] 294853 0
Efficacy will be determined during an acute phase (day 0, 0-24 hours) and a delayed phase (day 1 to day 10)
Secondary outcome [1] 314221 0
Frequency and/or severity of acute and/or delayed vomiting.
Methods and tools used: Rhodes Inventory of Nausea, Vomiting and Retching (RINV).
Timepoint [1] 314221 0
Efficacy will be determined during an acute phase (day 0, 0-24 hours) and a delayed phase (day 1 to day 10)
Secondary outcome [2] 314222 0
Frequency and severity of acute and delayed retching.
Methods and tools used: Rhodes Inventory of Nausea, Vomiting and Retching (RINV).
Timepoint [2] 314222 0
Efficacy will be determined during an acute phase (day 0, 0-24 hours) and a delayed phase (day 1 to day 10)
Secondary outcome [3] 314223 0
Adequacy of cannabinoid extract blinding.
Methods and tools used: Questionnaire will be used to ask each participant the following questions 'Do you think you received the placebo comparator of the cannabis extract medication and why do you think this?'
Timepoint [3] 314223 0
Efficacy will be determined during an acute phase (day 0, 0-24 hours) and a delayed phase (day 1 to day 10)
Secondary outcome [4] 314224 0
Changes in nutrition status.
Methods and tools used: Patient Generated - Subjective Global Assessment (PG-SGA)
Timepoint [4] 314224 0
Efficacy will be determined during an acute phase (day 0, 0-24 hours) and a delayed phase (day 1 to day 10)
Secondary outcome [5] 314225 0
Prevalence and/or severity of symptoms associated with treatment.
Methods and tools used: Edmonton Symptom Assessment Scale (ESAS)
Timepoint [5] 314225 0
Efficacy will be determined during an acute phase (day 0, 0-24 hours) and a delayed phase (day 1 to day 10)
Secondary outcome [6] 314226 0
Changes in quality of life.
Methods and tools used: FACT-G and FACIT-F questionnaires.
Timepoint [6] 314226 0
Efficacy will be determined during an acute phase (day 0, 0-24 hours) and a delayed phase (day 1 to day 10)
Secondary outcome [7] 314227 0
Changes in quality of life caused by nausea and vomiting.
Methods and tools used: FACT-G and FACIT-F questionnaires.
Timepoint [7] 314227 0
Efficacy will be determined during an acute phase (day 0, 0-24 hours) and a delayed phase (day 1 to day 10)
Secondary outcome [8] 314228 0
Patient adherence to the intervention.
Methods and tools used: Treatment Adherence Questionnaire/Table
Timepoint [8] 314228 0
Efficacy will be determined during an acute phase (day 0, 0-24 hours) and a delayed phase (day 1 to day 10)
Secondary outcome [9] 314229 0
Influence of previously identified factors that affect the generation of chemotherapy induced nausea and vomiting (CINV).
Methods and tools used: The Functional Living Index-Emesis-5 Day Recall (FLIE-5DR)
Timepoint [9] 314229 0
Efficacy will be determined during an acute phase (day 0, 0-24 hours) and a delayed phase (day 1 to day 10)

Eligibility
Key inclusion criteria
Patients meeting all of the following inclusion criteria will be included in the study:
1) Chemotherapy-naive patients receiving moderate-highly emetogenicity chemotherapy.
2) Males and females equal to or greater than 18 years old.
3) Life expectancy >3 months.
4) ECOG performance status equal to or less than 2.
5) Baseline Karnofsky score >60.
6) No concurrent neoplasms or illness that induces nausea independent of chemotherapy.
7) No self-prescribed therapies or complimentary products used for nausea such as ginger.
8) Receiving serotonin 5HT3 or NK1 receptor antagonist medications.
9) Can be reasonably expected to be able to complete the CINV assessment tools.
10) Have provided 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) Patients requiring radiotherapy.
2) Previous adverse reaction to or contraindicated to the standard anti-emetics proposed in the study.
3) Pregnant or breast-feeding.
4) Concurrent use of other cannabinoid-containing products.
5) History of adverse reactions to cannabinoids.
6) Patients with malignancies of gastrointestinal tract / gastrointestinal diseases or nausea and vomiting due to reasons other than chemotherapy.
7) Thrombocytopenia or patients undergoing chemotherapy that, according to physician discretion, is likely to cause thrombocytopenia (platelets <50 x 10^9/L).
8) Currently prescribed warfarin or on any other form of anti-coagulant therapy.

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)
Participant identification numbers will be assigned sequentially to the participants as soon as the informed consent form is signed. Participants will be randomly assigned using a computer generated randomisation sequence. The randomisation sequence will be kept separately from the study investigators and will, be generated by an independent researcher/statistician.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised in a 1:1 ratio using a stratified block design, stratified by chemotherapy category (moderate or high emetogenic chemotherapy), to receive either standard therapy alone plus placebo, or standard therapy plus whole plant cannabidiol ‘rich’ extract
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
We anticipate that the proportion of patients who experience CINV with adjunctive cannabinoid therapy will be approximately 20% better, that is approximately 70%.

Using Fisher’s exact test for comparing two proportions, power set at 80% and a two-tailed significance level of 0.05, the number of participants required in each group will be 93. Accounting for an attrition rate of 20%, the required sample size is 112 per group (n = 224 total participants to complete clinical trial)

* Analyses will be conducted using intention-to-treat principles i.e. the consent process will maximise outcome data collection and attempt to assess nausea symptoms for everyone, and will retain original group allocation despite compliance levels.
* Descriptive statistics will be presented as mean ± standard deviation, or median with range, as appropriate.
* Parametric analyses will be used for all continuous variables. Non-parametric equivalent will be used for data that are not normally distributed.
* Chi–square analyses will determine associations between categorical variables and will allow assessment of whether the incidence, severity and type of nausea differ between the two groups.
* Pearson correlation analysis of continuous variables will be performed.
* Repeated measures ANOVA will be conducted to detect between group differences over time as per our statistician recommendations.
* Statistical significance will be set at p<0.05 level (two-tailed).
* Data will be analysed using Stata 13.1 MP for Mac or later.

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
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] 3717 0
Royal North Shore Hospital - St Leonards

Funding & Sponsors
Funding source category [1] 291128 0
Government body
Name [1] 291128 0
New South Wales Government Health
Address [1] 291128 0
73 Miller Street
North Sydney NSW 2059
Country [1] 291128 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
Level 6
Jane Foss Russell Building
Room G02, The University of Sydney, NSW 2006
Country
Australia
Secondary sponsor category [1] 289805 0
None
Name [1] 289805 0
Address [1] 289805 0
Country [1] 289805 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 292707 0
Royal North Shore Hospital Human Research Ethics Committee
Ethics committee address [1] 292707 0
North Shore Private Hospital
Ethics Committee Executive Suiten
North Shore Private Hospital 3, Westbourne St
ST LEONARDS NSW 2065
Ethics committee country [1] 292707 0
Australia
Date submitted for ethics approval [1] 292707 0
01/10/2015
Approval date [1] 292707 0
Ethics approval number [1] 292707 0

Summary
Brief summary
This clinical trial aims to compare the safety and efficacy of Cannabinoid Nasal Spray Micelle as an adjunct therapy for the treatment of chemotherapy induced nausea and vomiting in chemotherapy-naive oncology patients.

Who is it for? All chemotherapy-naive patients receiving moderate-high emetogenicity chemotherapy aged 18 years or over.

Study details: All participants in this study are randomly allocated to one of the two groups. Participants in one group will use a cannabinoid derived nasal spray in addition to standard nausea and vomiting treatment for five chemotherapy days. Participants in the second group will use a nasal placebo spray in addition to standard nausea and vomiting treatment for five chemotherapy days.

There is a 50% chance of being assigned to one of the two groups. Participants are expected to have routine blood tests as standard of care provided by the medical oncologists. In addition, participants are expected to complete multiple questionnaires provided by the study investigators. The questionnaires will include 1) One RINV questionnaire per day (one on the day of chemotherapy, and one each of the 4 days post chemotherapy. 2) Two FACT-G/FACIT-F questionnaires per cycle. 3) One FLIE-5DR questionnaire per cycle. 4) Two ESAS questionnaires per cycle. 5) One Adherence Questionnaire for each day the participant receives the study medication.

This study aims to see a 'complete response', where 'complete response' is defined as no vomiting and no use of rescue medication.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 56650 0
Prof Luis Vitetta
Address 56650 0
Medlab Pty Ltd
66 McCauley St.
Alexandria, NSW 2015
Country 56650 0
Australia
Phone 56650 0
+61 (02) 8094 1939
Fax 56650 0
Email 56650 0
luis_vitetta@medlab.co
Contact person for public queries
Name 56651 0
Dr Samantha Coulson
Address 56651 0
Medlab Pty Ltd
66 McCauley St.
Alexandria, NSW 2015
Country 56651 0
Australia
Phone 56651 0
+61 (02) 8188 0311
Fax 56651 0
Email 56651 0
samantha_coulson@medlab.co
Contact person for scientific queries
Name 56652 0
Prof Luis Vitetta
Address 56652 0
Medlab Pty Ltd
66 McCauley St.
Alexandria, NSW 2015
Country 56652 0
Australia
Phone 56652 0
+61 (02) 8094 1939
Fax 56652 0
Email 56652 0
luis_vitetta@medlab.co

No information has been provided regarding IPD availability
Summary results
No Results