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Trial registered on ANZCTR


Registration number
ACTRN12618001794291
Ethics application status
Approved
Date submitted
3/10/2018
Date registered
2/11/2018
Date last updated
2/11/2018
Date data sharing statement initially provided
2/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Prophylactic Pregabalin for Head and Neck Radiotherapy Patients - Pilot
Scientific title
Pilot Randomised Controlled Trial of Prophylactic Pregabalin for Pain in Radical Head and Neck Cancer Patients Receiving Radiotherapy
Secondary ID [1] 296243 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Radiotherapy-related pain 309891 0
Condition category
Condition code
Cancer 308678 308678 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: Prophylactic Pregabalin - Oral, taken in addition to standard of care analgesia given to treat radiotherapy-related pain
Pregabalin starting dose = 75mg twice per day for 3 days
Increase dose as follows:
75mg in the morning and 150mg in the evening for 3 days
150mg twice per day for 3 days
150mg in the morning and 225mg in the evening for 3 days
225mg twice per day for 3 days
225mg in the morning and 300mg in the evening for 3 days
300mg twice per day to continue as tolerated
The threshold effective dose for trial purposes will be any dose including or higher than 225mg twice per day
Pregabalin will be taken orally, however, if patients become unable to take capsules orally during the course of radiotherapy, they can take pregabalin via feeding tube by opening the capsule and dissolving the contents of the capsule in sterile water.

Treatment Cessation:
Start down titration of pregabalin in a similar schedule to escalation at the same time and rate of opiate reduction (i.e. from 2-6 weeks following treatment, as clinically indicated).
i.e. once pain scores reduce and oral nutrition increases, reduce pregabalin as follows
225mg in the morning and 300mg in the evening for 3 days
225mg twice per day for 3 days
150mg in the morning and 225mg in the evening for 3 days
150mg twice per day for 3 days
75mg in the morning and 150mg in the evening for 3 days
75mg twice per day for 3 days
Stop all pregabalin

Dose Adjustments:
If patients develop G1-2 toxicity (CTCAEv4) related to pregabalin, pregabalin doses should be reduced to the next dose band down (i.e. reduce by 75mg at a time) until side-effects are tolerable. Aim to treat patients with the highest tolerable dose.
If patients develop G3 or G4 toxicity related to pregabalin, or persistent G1 or 2 toxicity with pregabalin, the drug will be stopped.
Pregabalin will not be given to patients taking buprenorphine or propoxyphene. If possible buprenorphine/propoxyphene will be changed to a different analgesic before commencing on the trial.
Stop treatment if patients develop severe thrombocytopenia (unrelated to chemotherapy), severe hypersensitivity reactions, suicidal ideation or seizures.

Drug Accountability:
Tablet counts will be performed each week to assess compliance with pregabalin. Patients will be asked to bring in all used blister packs for counting.

Arm 2: Standard of Care analgesia to treat radiotherapy-related pain
Intervention code [1] 312570 0
Treatment: Drugs
Comparator / control treatment
Arm 2 will not be treated with prophylactic pregabalin and will receive standard of care analgesia to treat radiotherapy-related pain. This involves introduction of simple analgesia (paracetamol and ibuprofen/aspirin and topical anaestheics e.g. xylocain liquid orally), stepping up to opiate analgesia when pain increases. Opiate analgeisa is titrated according to pain.
Control group
Active

Outcomes
Primary outcome [1] 307646 0
Proportion of patients who contiue on trial to completion. This will be assessed by audit of attendance logs
Timepoint [1] 307646 0
6 weeks post-treatment and 1 year post-treatment
Primary outcome [2] 307650 0
Proportion of patients who tolerate doses of pregabalin above 225mg twice per day. This will be assessed by data linkage to medical records.
Timepoint [2] 307650 0
6 weeks post-treatment
Primary outcome [3] 307655 0
proportion of patients who have accurate and complete radiotherapy-related pain assessments. This will be assessed by audit of attendance logs
Timepoint [3] 307655 0
6-weeks post treatment and 1 year post-treatment
Secondary outcome [1] 352502 0
Nil- this is a Pilot study.
Timepoint [1] 352502 0
N/A

Eligibility
Key inclusion criteria
• Gender: male and female
• Age: >18 years
• ECOG 0-2
• Patients receiving curative radiotherapy to the head and neck area to treat mucosal squamous cell carcinomas (SCC), with or without chemotherapy/cetuximab
• Both P16 positive and negative SCC (a known variant in histology)
• Patients undergoing radiotherapy (RT) as both adjuvant and radical treatment
• Willingness to give written informed consent
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Patients receiving palliative radiotherapy to the head and neck.
• Patients in whom pregabalin is contraindicated E.g.
o intolerance or allergy to pregabalin/gabapentin
o patients on buprenorphine or propoxyphene
• Patients on neuroleptic medication or other neuropathic agents for other medical conditions
• Inability to provide informed consent
• Inability to complete the visual aspects of the questionnaires without assistance (other then explanation)
• Patients with moderate/severe renal impairment with GFR (glomerular filtration rate) of <50ml/min as calculated according to Cockroft-Gault formula using screening blood test
• Platelet count <100
• Absolute neutrophil count <1.5x109/L
• Alanine aminotransferase (ALT) >2.5x upper limit of normal
• Patients who are pregnant or lactating
• Previous suicidal ideation

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)
Allocation is concealed
Randomisation by the statistician (non-clinical member of the team ) or someone who is not a member of the trial team by computer generated code based on stratification:
1) whether the patient is to receive concurrent systemic anticancer treatment (i.e. chemotherapy or cetuximab)
2) whether patients are due to have radiotherapy to one or both sides of the neck.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Dynamic (adaptive) random allocation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Accurate sample size calculation for this study is limited because pregabalin has not been used in this population. The number of patients for this pilot is based on the number of patients we estimate to recruit over the course of 12 months. St George Cancer Centre treats approximately 45 patients with HNC each year with curative radiotherapy and we feel it is realistic to hope to recruit 30 patients in a 12 month period.

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] 12078 0
St George Hospital - Kogarah
Recruitment postcode(s) [1] 24240 0
2217 - Kogarah

Funding & Sponsors
Funding source category [1] 300842 0
Hospital
Name [1] 300842 0
St George Hospital
Address [1] 300842 0
Gray Street
Kogarah
NSW 2217
Country [1] 300842 0
Australia
Primary sponsor type
Hospital
Name
South Eastern Sydney Local Health District
Address
District Executive Unit, Level 4
The Sutherland Hospital & Community Health Service
Cnr The Kingsway & Kareena Road
CARINGBAH NSW 2229
Country
Australia
Secondary sponsor category [1] 300389 0
None
Name [1] 300389 0
Address [1] 300389 0
Country [1] 300389 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301610 0
South Eastern Sydney Local Health District HREC
Ethics committee address [1] 301610 0
G71 East Wing Edmund Blacket Building,
Prince of Wales Hospital
Randwick
NSW 2031
Ethics committee country [1] 301610 0
Australia
Date submitted for ethics approval [1] 301610 0
Approval date [1] 301610 0
27/09/2018
Ethics approval number [1] 301610 0
17/278 (HREC/18/POWH/325)

Summary
Brief summary
The purpose of this study is to investigate whether it is possible to treat patients who are receiving head/neck cancer radiotherapy with a drug called pregabalin, targeting pain before it has arisen.

Who is it for?
You may be eligible for this study if you are aged over 18 and are receiving curative radiotherapy to the head and neck area to treat squamous cell carcinoma

Study details
Participants in this study will be randomised (by chance) into one of two groups. One group will continue standard care, including radiotherapy treatment with standard pain-killers to treat the radiotherapy-related pain. The other group will take a medication called pregablin during the course of their radiotherapy. Pregabalin will be prescribed in addition to the standard pain-killers used to treat radiotherapy-related pain.
All participants will receive standard of care radiotherapy and will undergo the routine tests required for treatment including scans before treatment and blood tests once a week whilst having radiotherapy. In addition, all patients in the trial will be asked to complete weekly pain questionnaires during radiotherapy and swallowing questionnaires at 6 weeks, 12 weeks, 24 weeks and 52 weeks after completion of radiotherapy.

It is hoped this research will provide evidence to support a larger study to see Pregablin reduces the swallowing pain that is often experienced during head and neck radiotherapy.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 87546 0
Dr Andrej Bece
Address 87546 0
Clinical Research Unit - Radiation Oncology
Level 1 Pitney Building
St George Hospital
Kogarah
NSW 2217
Country 87546 0
Australia
Phone 87546 0
+61 2 9113 4821
Fax 87546 0
+61 2 9113 4822
Email 87546 0
Andrej.Bece@health.nsw.gov.au
Contact person for public queries
Name 87547 0
Ms Helen Cox
Address 87547 0
Clinical Research Unit - Radiation Oncology
Level 1 Pitney Building
St George Hospital
Kogarah
NSW 2217
Country 87547 0
Australia
Phone 87547 0
+61 2 9113 1922
Fax 87547 0
+61 2 9113 4822
Email 87547 0
Helen.Cox2@health.nsw.gov.au
Contact person for scientific queries
Name 87548 0
Ms Helen Cox
Address 87548 0
Clinical Research Unit - Radiation Oncology
Level 1 Pitney Building
St George Hospital
Kogarah
NSW 2217
Country 87548 0
Australia
Phone 87548 0
+61 2 9113 1922
Fax 87548 0
+61 2 9113 4822
Email 87548 0
Helen.Cox2@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
The IPD will not be shared as this is a pilot trial looking at the feasibility of running a larger RCT. The subject of the trial is very specific and is unlikely to be of use to other groups collecting evidence for meta-analyses. The data will be stored securely at a local level and the data collected will be accessible to the research department at St george.
What supporting documents are/will be available?
Study protocol
Informed consent form
Clinical study report
Ethical approval
Attachments/websites
Type [1] 72 0
Informed consent form
URL/details/comments [1] 72 0
Type [2] 74 0
Study protocol
URL/details/comments [2] 74 0
Type [3] 75 0
Clinical study report
URL/details/comments [3] 75 0
Type [4] 76 0
Ethical approval
URL/details/comments [4] 76 0
Summary results
Not applicable