Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000328875
Ethics application status
Approved
Date submitted
7/08/2020
Date registered
23/03/2021
Date last updated
3/10/2023
Date data sharing statement initially provided
23/03/2021
Date results information initially provided
3/10/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Ketamine for Cancer Pain
Scientific title
Sublingual Ketamine as Breakthrough Analgesia in Patients with Advanced Cancer -- A Feasibility Study
Secondary ID [1] 302243 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Cancer 318505 0
Moderate to Severe Pain 318506 0
Inadequate analgesia 318507 0
Condition category
Condition code
Cancer 316509 316509 0 0
Any cancer
Anaesthesiology 316510 316510 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be randomised into one of the following sequences to determine the order of sublingual ketamine (A) and placebo wafer (P):
- AP AP AP
- AP AP PA
- AP PA AP
- AP PA PA
- AP AP AP
- PA AP PA
- PA PA AP
- PA PA PA

Each sequence consists of 3 pairs. Each pair consists of a period (7 days) of A and a period of P. First 2 days of each period will be considered washout days in the analysis. This means that the participants will take the study medication as instructed, but when analysing the results, these two days will be considered washout days rather than treatment days.
For the next 5 of the 7 days during the period, participants will take study medication as per instruction, and the results will be analysed accordingly.

The total duration of the study will be six weeks.

Participants will be instructed to use the study drug as a first line breakthrough analgesia.
The study drug will be either Sublingual ketamine wafer 25 mg or a placebo wafer.
They will take one dose of the study drug no more than every 3 hours, with a maximum of 3 doses per day. When they have reached the maximum allowable study medication per day, they will be taking their usual pain medication as prescribed by their treating physician. This may be their usual short acting opioid medication such as oxycodone or morphine.

Participants will be required to complete a study diary which includes the information on the study medication and other analgesic agents taken that day, and will also record any potential side effects.

There will be weekly follow up after each 7-day period through either videoconferencing or face-to-face review at the outpatient clinic in the hospital. Participant will be asked to present the Webster-Pak to show the study staff the exact amount used or left in the medication pack.
Intervention code [1] 318242 0
Treatment: Drugs
Comparator / control treatment
Placebo microcellulose wafer
Control group
Placebo

Outcomes
Primary outcome [1] 324651 0
Completion of two cycles in thirty participants over 12 month period with the existing resource.
i.e. less than 25 % attrition rate

This will be assessed by the project staff at the end of each seven-day period through videoconferencing appointment.
Assessment will consist of:
- visual inspection of the medication pack to confirm the number of the medication consumed and medication left.
- collection of the study diary, Quality of Life Questionnaire (AQol-6D), and Drug Efficacy Questionnaire (including SAT-1 (Self-assessment of treatment-1))
Timepoint [1] 324651 0
Twelve months period after commencement of the study
Secondary outcome [1] 385340 0
Attrition rate measure by completion of two cycles over a twelve-month period. This will be measured by attendance/absence at the weekly (end of each 7-day period) follow-up.
Timepoint [1] 385340 0
Twelve months period after commencement of the study
Secondary outcome [2] 386614 0
Within-patient and treatment-by-patient variances for the pain severity as assessed by Oral Morphine Equivalent Daily Dose (OMEDD) in the Study Diary Section A & B
Timepoint [2] 386614 0
This will be done daily for the duration of the study, i.e. 6 weeks
Secondary outcome [3] 392176 0
Within-patient and treatment-by-patient variances for pain impact, as assessed by EQ-5D questionnaire (included in Study Dairy)
Timepoint [3] 392176 0
Daily for the duration of the study, i.e. 6 weeks.
Secondary outcome [4] 392177 0
Side effects/tolerability, as assessed by KSET (Ketamine Side Effect Tool) questionnaire.

Timepoint [4] 392177 0
This will be assessed every 7 days
Secondary outcome [5] 392178 0
Quality of life as assessed by AQoL-6D Questionnaire

Timepoint [5] 392178 0
Assessed every 7 days
Secondary outcome [6] 392179 0
Resources-cost
- total cost, as assessed by the budget/expenditure
- The income and expenditure will be itemised clearly on the research fund created for this project.
- Expected expenditure include: cost of the medication, pharmacy fees (including trial establishment fees, packaging and drug dispensing), CTN application fee.
Timepoint [6] 392179 0
Twelve months period after commencement of the study
Secondary outcome [7] 392180 0
Resources- infrastructure support
1. time required of the study staff - all the staff time spent on the study will be recorded on the database
2. adequacy of existing consultation room and computer availability, and provision of stationary
Timepoint [7] 392180 0
Twelve months period after commencement of the study
Secondary outcome [8] 392181 0
Resources: willingness of clinicians to recruit participants, as assessed by percentage of participants being recruited by clinician specialities.
Timepoint [8] 392181 0
Twelve months period after commencement of the study
Secondary outcome [9] 392182 0
Resources: acceptance of the patients to participate as assessed by recruitment rate
Timepoint [9] 392182 0
Twelve months period after commencement of the study
Secondary outcome [10] 392183 0
Resources: participants discriminance of active vs placebo medication as assessed by the 5 specific questions in study diary
Timepoint [10] 392183 0
Twelve months period after commencement of the study
Secondary outcome [11] 392184 0
Resources: practicality of follow-up procedures, videoconferencing calls and face-to-face visit to the hospital, as assessed by staff notes for conducting these sessions.
Timepoint [11] 392184 0
Twelve months period after commencement of the study
Secondary outcome [12] 393024 0
Within-patient and treatment-by-patient variances for drug efficacy questionnaire in the Study Diary Section D
Timepoint [12] 393024 0
This will be recorded daily for the entire duration of the study, i.e. 6 weeks
Secondary outcome [13] 393025 0
Within-patient and treatment-by-patient variances for the outcome in Self-Assessment of Treatment instrument (SAT-I). This is a validated self-assessment tool developed initially to assess improvement and satisfaction with treatment in patients with neuropathic pain condition.
Timepoint [13] 393025 0
This will be assessed with periodic Drug Efficacy questionnaire every 7 days (ie. every period)
Secondary outcome [14] 393026 0
Disease progression measures from the Periodic review data form including Australian-modified Karnofsky Performance Status (AKPS), Liver and Renal Function Test and Weight.
Timepoint [14] 393026 0
Assessed every 7 days
Secondary outcome [15] 393027 0
EQ-5D questionnaire (included in Study Diary)
Timepoint [15] 393027 0
Assessed daily for the duration of the study

Eligibility
Key inclusion criteria
1. Adult patients with diagnosis of advanced cancer
2. Weight >40 kg, and BMI between 18-40 kg•m-2
3. Moderate to severe pain associated with the cancer diagnosis requiring ongoing opioid analgesia at >60 mg of OMEDD (oral morphine equivalent daily dose)
4. Self-reporting sub-optimal pain control with current analgesia
5. Willingness to provide informed consent and willingness to participate and comply with the study requirements.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Women lactating, pregnant or of childbearing potential who are not willing to avoid becoming pregnant during the study.
2. Participants who are receiving ketamine medication through any route of administration as part their treatment regimen.
3. Participants with a history of raised intra-cranial pressure, epilepsy, raised intra-ocular pressure, severe cardiac failure, or uncontrolled hypertension
4. Participants with a history of cognitive impairment which may interfere with their ability to understand the study requirements.
5. Participants with DSM-V diagnosis of psychotic disorders or dissociative disorders which may resemble the adverse effect of the study medication
6. The requirement of analgesia is expected to decrease following recruitment into the study.
7. Participants with life expectancy of less than six weeks

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)
Each participant will be given a study ID. Treatment sequence corresponding to the study ID will be blinded to the recruiter, the patient, and the study investigator. The study pharmacist will be blinded to the enrolled participants.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Each Study ID will be assigned to one of the 8 sequences using complete randomisation procedure generated by R Package “randomizr”
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
Crossover
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/04/2021
Actual
5/09/2021
Date of last participant enrolment
Anticipated
31/12/2022
Actual
21/03/2023
Date of last data collection
Anticipated
19/02/2023
Actual
21/03/2023
Sample size
Target
32
Accrual to date
Final
29
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 17196 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 17197 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment postcode(s) [1] 30902 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 306380 0
Charities/Societies/Foundations
Name [1] 306380 0
Australia and New Zealand College of Anaesthetists
Country [1] 306380 0
Australia
Primary sponsor type
Hospital
Name
Chris O'brien Lifehouse
Address
117-119 Missenden Road, Camperdown, NSW 2050
Country
Australia
Secondary sponsor category [1] 308368 0
None
Name [1] 308368 0
Address [1] 308368 0
Country [1] 308368 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306577 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 306577 0
Research Ethics and Governance Office (REGO)
Royal Prince Alfred Hospital
Missenden Road
CAMPERDOWN NSW 2050
Ethics committee country [1] 306577 0
Australia
Date submitted for ethics approval [1] 306577 0
26/01/2021
Approval date [1] 306577 0
23/02/2021
Ethics approval number [1] 306577 0
Protocol no. X21-0017 & 2021/ETH00119

Summary
Brief summary

The purpose of this study is to determine the use of sublingual ketamine drug to help with relieving pain for patients with advanced cancer.

Who is it for?
You may be eligible for this study if you are aged 18 years or older, have significant pain associated with advanced cancer, your body weight is more than 40 kg and are willing to comply with the study requirements.

Study details
Participants in this study will receive three cycles of two treatment drugs in random orders:
1. sublingual ketamine wafer (flat tablet placing under tongue) for 7 days
2. non-active (sham) wafer for 7 days
The first 2 days of each period will be considered analytical washout days and hence will not be analysed for efficacy regardless of whether study medication is taken.

Participants will be expected to complete a daily and weekly questionnaires and also have interviews with study staff through either video-conferencing or visit to hospital after each 7-day study period.

It is hoped that this research will determine if a larger trial can be completed on evaluating the effect of sublingual ketamine drug as pain relief for management of moderate to severe pain in patients with advanced cancer.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 104346 0
Dr Yi-Ching Lee
Address 104346 0
Pain Management Centre, Royal Prince Alfred Hospital
Level 4, QEII, 50 Missenden Rd, Camperdown NSW 2050
Country 104346 0
Australia
Phone 104346 0
+61 2 9515 3854
Fax 104346 0
+61 2 9515 9831
Email 104346 0
[email protected]
Contact person for public queries
Name 104347 0
Mr Kenny Lee
Address 104347 0
Clinic A, Level 2, Chris O'Brien Lifehouse
117-119 Missenden Rd, Camperdown NSW 2050
Country 104347 0
Australia
Phone 104347 0
+61 2 85141349
Fax 104347 0
+61 2 9515 9831
Email 104347 0
[email protected]
Contact person for scientific queries
Name 104348 0
Dr Andy Wang
Address 104348 0
50 Missenden Road
Level 4
Department of Anaesthesia
Royal Prince Alfred Hospital
Camperdown NSW 2050
Country 104348 0
Australia
Phone 104348 0
+61 2 9515 8507
Fax 104348 0
+61 2 9519 2455
Email 104348 0
[email protected]

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


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
EmbasePharmacologic Management of Persistent Pain in Cancer Survivors.2022https://dx.doi.org/10.1007/s40265-022-01675-6
N.B. These documents automatically identified may not have been verified by the study sponsor.