Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000876695
Ethics application status
Approved
Date submitted
7/07/2014
Date registered
15/08/2014
Date last updated
6/08/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Improving radiotherapy outcomes with smoking cessation: Feasibility trial in head and neck cancer patients
Scientific title
Improving radiotherapy outcomes in head and neck cancer patients: A preliminary comparison of smoking cessation intervention ‘Varenicline plus support’ with ‘treatment as usual’
Secondary ID [1] 284872 0
Nil
Universal Trial Number (UTN)
U1111-1158-4261
Trial acronym
Health Steps
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Smoking 292305 0
Head and neck cancer 292306 0
Radiotherapy 292307 0
Condition category
Condition code
Cancer 292641 292641 0 0
Head and neck
Mental Health 293060 293060 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Multicomponent Smoking Cessation Intervention (Varenicline + Behaviour Change Counselling; “Stop Smoking Support”)

Varenicline will be administered orally via tablets in accordance with approved labelling. Dose titration will be: 0.5 mg/d for days 1 to 3; 1 mg/d for days 4 to 7; and 2 mg/d (the target dose) from days 8 to 84. In accordance with recommendations from the Pharmaceutical Benefits Advisory Committee (2009), patients who successfully complete the initial 3-month course will be offered an additional 3-month course (2mg/d) to assist with maintaining abstinence.

Varenicline will be provided at no cost to participants. The initial course of Varenicline will be distributed at treatment planning. Patients who successfully complete the initial 3 month course will receive a further 84 day supply of Varenicline during their appointment with the radiation oncologist (RO) following RT completion. Medication adherence will be evaluated via self-report and pill count. Medication compliance will be explicitly discussed by the RO and psychologist as part of the Behaviour Change Counselling Intervention. The psychologist will also administer an established medication adherence questionnaire at each appointment. At each follow-up assessment, participants will be asked to return the blister packs administered at the preceding timepoint. Any missed medication will be retained by the research staff and counted. Any outstanding medication will be returned to the participant along with the next instalment of medication.

At the time of treatment planning (simulation), RO's will offer brief medical advice to quit. This brief intervention is designed to supplement Varenicline administration to assist patients to stop smoking. Brief advice will also be integrated into routine consultations.

Intervention participants will also receive up to 10 sessions of manual-based motivational interviewing and cognitive behaviour therapy (CBT) delivered by a psychologist. Sessions will include 2 x ‘pre-quit’ and 1 x ‘quit day’ sessions (of up to one hour) and 7 x ‘relapse prevention’ sessions (of up to 30min). Sessions will be weekly for the first four weeks and approximately fortnightly-monthly thereafter (as needed and according to patient preference). To position smoking cessation as central to radiotherapy, sessions will be offered in the radiotherapy outpatient department. Telephone sessions will be offered as an alternative, according to patient preference. Counselling is included given its efficacy at helping smokers quit (Fiore et al., 2008).
Intervention code [1] 289680 0
Treatment: Drugs
Intervention code [2] 289755 0
Behaviour
Intervention code [3] 289756 0
Lifestyle
Comparator / control treatment
Treatment as Usual
Participants assigned to this group will receive standard radiotherapy treatment from the RO. In regard to smoking cessation they will receive the standard NSW Health tobacco assessment and smoking cessation advice; they will not be prescribed Varenicline and will not receive additional smoking cessation counselling from a psychologist.
Control group
Active

Outcomes
Primary outcome [1] 292480 0
Feasibility and acceptability as indexed by:
a. Accrual (consent and retention rates)
b. Appointment compliance (attended vs. rescheduled with reason vs. failed to attend for the follow-up, psychologist and RO appointments)
c. Medication compliance (self-reported Morisky Medication Adherence scores and pill count)
d. Medication tolerability (Side effects as assessed by Varenicline Side Effects Checklist and PHQ-9/ ASRM as needed)
Timepoint [1] 292480 0
Data collection will be ongoing throughout the trial. Questionnaires for compliance and tolerability will be administered at every assessment occasion (baseline, final week of radiotherapy, three months post radiotherapy, six months post radiotherapy; 12 and 24 weeks post treatment planning). Intervention participants will also complete these questionnaires during their psychology and/ or RO appointments.
Secondary outcome [1] 309057 0
Tumour response as assessed with PET scans

Timepoint [1] 309057 0
Timepoint: 3 and 6 months post radiotherapy
Secondary outcome [2] 309058 0
Seven day point prevalence abstinence as measured by the Time Line Follow Back (TLFB)
Timepoint [2] 309058 0
Timepoint: every assessment occasion (baseline, final week of radiotherapy, three months post radiotherapy, six months post radiotherapy; 12 and 24 weeks post treatment planning)
Secondary outcome [3] 309059 0
Continuous abstinence as measured by the Time Line Follow Back (TLFB)
Timepoint [3] 309059 0
Timepoint: every assessment occasion (baseline, final week of radiotherapy, three months post radiotherapy, six months post radiotherapy; 12 and 24 weeks post treatment planning)
Secondary outcome [4] 309060 0
Biochemical verification of smoking status as measured by expired carbon monoxide
Timepoint [4] 309060 0
Timepoint: every assessment occasion (baseline, final week of radiotherapy, three months post radiotherapy, six months post radiotherapy; 12 and 24 weeks post treatment planning)
Secondary outcome [5] 309061 0
Treatment completion extracted from hospital chart review
Timepoint [5] 309061 0
Timepoint: 6 months post radiotherapy
Secondary outcome [6] 309062 0
Total radiotherapy treatment time extracted from hospital chart review
Timepoint [6] 309062 0
Timepoint: 6 months post radiotherapy
Secondary outcome [7] 309063 0
Unplanned hospital visits extracted from hospital chart review
Timepoint [7] 309063 0
Timepoint: 6 months post radiotherapy
Secondary outcome [8] 309064 0
Length of stay in hospital extracted from hospital chart review
Timepoint [8] 309064 0
Timepoint: 6 months post radiotherapy
Secondary outcome [9] 309065 0
Weight as extracted from hospital chart review
Timepoint [9] 309065 0
Timepoint: Baseline and 6 months post radiotherapy
Secondary outcome [10] 309066 0
Mucositis score as measured by the Common Terminology Criteria for Adverse Events (CTCAE)
Timepoint [10] 309066 0
Timepoint: Baseline, final week of radiotherapy, three months post radiotherapy.
Secondary outcome [11] 309067 0
Mortality data extracted from hospital chart review
Timepoint [11] 309067 0
Timepoint: 6 months post radiotherapy
Secondary outcome [12] 309068 0
Number of quit attempts as assessed through semi-structured interview
Timepoint [12] 309068 0
Timepoint: every assessment occasion (baseline, final week of radiotherapy, three months post radiotherapy, six months post radiotherapy; 12 and 24 weeks post treatment planning)
Secondary outcome [13] 309070 0
Readiness to change as assessed by a five item questionnaire based on the Transtheoretical Model of Behaviour Change
Timepoint [13] 309070 0
Timepoint: Baseline
Secondary outcome [14] 309072 0
Self Reported nicotine dependence as assessed by Fagerstrom Test for Nicotine Dependence (FTND)
Timepoint [14] 309072 0
Timepoint: every assessment occasion (baseline, final week of radiotherapy, three months post radiotherapy, six months post radiotherapy; 12 and 24 weeks post treatment planning)
Secondary outcome [15] 309073 0
Self reported alcohol dependence as assessed by the Alcohol Use Disorders Identification Test (AUDIT)
Timepoint [15] 309073 0
Timepoint: Baseline
Secondary outcome [16] 309074 0
Recent (three-month) alcohol consumption as assessed by the Alcohol Use Disorders Identification Test – Consumption items
Timepoint [16] 309074 0
Timepoint: Baseline, 3 and 6 months post radiotherapy
Secondary outcome [17] 309075 0
Nicotine Withdrawal symptoms as assessed by the Minnesota Withdrawal Scale-Revised (MNWS-R)
Timepoint [17] 309075 0
Timepoint: every assessment occasion (baseline, final week of radiotherapy, three months post radiotherapy, six months post radiotherapy; 12 and 24 weeks post treatment planning)

Eligibility
Key inclusion criteria
- Self-report smoking at least 5 cigarettes per day (on average in the preceding 3 months)
- Diagnosed with Head and Neck Cancer (including skin)
- Scheduled to undergo radiotherapy (definitive or adjuvant) for head and neck cancer (curative intent)
- ECOG Performance Status score of <2 within 6 months of enrolment.
- Able to use Varenicline safely (based on medical, physical and psychiatric evaluation)
- Residing in the geographic area for at least 12 months.
- Able to communicate fluently in English and capable of giving written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Regular (daily) use of chewing tobacco, snuff/ snus, cigars, cigarillos, or pipes.
- Current use or recent discontinuation (<6 months) of Buproprion cannot have been used in the preceding 6 months.
- Women who are pregnant, planning a pregnancy within the next 12 months, or lactating.
- History of epilepsy or seizure disorder.
- History of kidney or liver disease, including transplant.
- Uncontrolled hypertension (SBP >160 or DBP >100).
- History of heart disease, stroke or MI, unstable angina, abnormal heart rhythms, or tachycardia
- Current acute suicidal ideation or self-reported suicide attempt in the last 12 months.
- Current diagnosis of unstable/ untreated major depression, bipolar disorder or psychotic disorder as determined by self-report (eligible if stable and compliant with treatment for >30 days).
- Previous allergic reaction to Varenicline.

Please note, that once patients are deemed to be eligible for the trial they will be required to refrain from starting non-study smoking cessation treatments (including, but not limited to, Nicotine Replacement Therapy, Buprenorphine, Psychological Intervention, Counselling). Patients who have already commenced NRT are eligible to participate.

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)
Potential participants will be recruited from the Calvary Mater Newcastle (CMN). A research assistant will work with clinic staff to identify potential participants. Potential participants will be identified by CMN staff in the month preceding the new patient clinic from the pool of patients who meet the following screening criteria:

1. Aged 18+
2. Diagnosis of head and neck cancer (including skin)
3. Scheduled to undergo radiotherapy (definitive or adjuvant) for head and neck cancer (curative intent)

Patients who meet the above criteria may be identified using treatment planning software (e.g. Varian or Mosaiq), discussion from team meetings, and/ or referral from hospital staff. Potential participants may also self-refer based on advertising material placed within the hospital. Initial communication with patients may be written, over the phone or in person.

Patients who meet the above criteria will be approached by a RO or CMN staff member at the new patient clinic.They will be provided with verbal information about the study and will undergo a brief screening interview to assess inclusion and exclusion criteria. Interested and eligible patients will be given a copy of the information statement to consider and advised that a member of the research team will be in contact to confirm interest.

Before they attend their treatment planning appointment, eligible patients who have agreed to be contacted will then be contacted by a member of the research team (e.g. research assistant or psychologist) to confirm interest. According to participant preference, this contact may be in person or over the phone. Uncontactable patients may also be sent written communication.

Patients agreeable to participate will be invited to attend a baseline assessment. This appointment will be scheduled before the patient is due to attend their treatment planning appointment. The researcher will take consent (verbal or written) and complete the baseline assessment. According to participant preference, this appointment may occur in person, or over the phone.

Once a member of the research team has completed the baseline assessment, treatment allocation will be randomised using a free online randomisation service – “sealed envelope” (https://www.sealedenvelope.com).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Once a member of the research team has completed the baseline assessment, treatment allocation will be randomised using a free online randomisation service – “sealed envelope” (https://www.sealedenvelope.com). Patients will be randomised prior to their treatment planning appointment with the RO.

Using the page created for the study, the staff member will be required to enter the unique study password, their email address and a unique identifier (patient initials and date of birth). Randomisation is instantaneous. The randomisation results are shown on-screen and emailed to both a chief investigator and to the randomiser.

The randomisation arms will be as follows:
Arm A: Treatment as Usual
Arm B: Multicomponent Smoking Cessation Intervention (Varenicline + Behaviour Change Counselling; “Stop Smoking Support”)

The free version of Sealed Envelope uses simple randomisation. Randomisation is also blocked (using random permuted blocks) to ensure that the groups are balanced periodically.

Treatment allocation will be concealed from all members of the research team until after randomisation. Assessors will remain blind to treatment allocation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
As this is a feasibility study no formal power calculations have been conducted. Rather, we intend to randomly allocate 40 patients to receive either stop smoking support or treatment as usual to assess feasibility (i.e. can HNC patients undergoing RT be recruited into a trial involving medication and smoking cessation counselling), adherence (to follow-up assessments, Varenicline and psychological support) and tolerability of Varenicline (i.e. side effects).

A Statistical Analysis Plan (SAP) will be developed within six months of enrolling the first participant.

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Participant recruitment difficulties
Other reasons/comments
Other reasons
Time limited funding: It was anticipated that one participant would be recruited per week and after a period of 9 months a target of 40 participants would be recruited. This target was based on the available evidenceon smoking prevalence,which indicates that approximately one-third of patients with head and neck cancer continue to smoke after diagnosis. The recruitment target was also based onstudy uptake in a previous pilot trial conducted by CIA Britton in the radiotherapy department at the Calvary Mater Newcastle. Inthe pilot trial 96% of HNC patients who were approach consented toparticipatein the trial and 90% completed the trial. Unfortunately, the project was not found to be feasible after only one participant was recruited to the study during the recruitment period. A higher than anticipatednumber of patients being treated in the Radiation Oncology Department at the CMN were found to be ineligible for the study, (meeting exclusion criteria i.e. heart disease, ex smokers or non-smokers).
Date of first participant enrolment
Anticipated
18/08/2014
Actual
3/10/2014
Date of last participant enrolment
Anticipated
Actual
3/10/2014
Date of last data collection
Anticipated
28/02/2015
Actual
13/02/2015
Sample size
Target
40
Accrual to date
Final
1
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 2674 0
Calvary Mater Newcastle - Waratah
Recruitment postcode(s) [1] 8345 0
2298 - Waratah

Funding & Sponsors
Funding source category [1] 289488 0
Hospital
Name [1] 289488 0
James Lawrie Head and Neck Cancer Research Grant Fund (Calvary Mater Newcastle)
Country [1] 289488 0
Australia
Primary sponsor type
Individual
Name
Dr Benjamin Britton
Address
Clinical and Health Psychologist

Postal Address:
Dept. Consultation-Liaison Psychiatry,
Box 51,
Calvary Mater Newcastle
Waratah NSW 2298

Street Address:
Calvary Mater Hospital
Edith Street
Waratah NSW 2298
Country
Australia
Secondary sponsor category [1] 288479 0
None
Name [1] 288479 0
Address [1] 288479 0
Country [1] 288479 0
Other collaborator category [1] 278020 0
University
Name [1] 278020 0
Priority Research Centre for Translational Neuroscience and Mental Health, University of Newcastle
Address [1] 278020 0
Level 5, McAuley Centre
Calvary Mater Hospital
Edith Street
Waratah, NSW, 2298
Country [1] 278020 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291244 0
Hunter New England Human Research
Ethics committee address [1] 291244 0
Ethics committee country [1] 291244 0
Australia
Date submitted for ethics approval [1] 291244 0
Approval date [1] 291244 0
08/04/2014
Ethics approval number [1] 291244 0
HREC/14/HNE/76
Ethics committee name [2] 291296 0
University of Newcastle Human Research Ethics Committee
Ethics committee address [2] 291296 0
Ethics committee country [2] 291296 0
Australia
Date submitted for ethics approval [2] 291296 0
05/05/2014
Approval date [2] 291296 0
28/05/2014
Ethics approval number [2] 291296 0
H-2014-0184

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 49478 0
Dr Benjamin Britton
Address 49478 0
Priority Research Centre for Translational Neuroscience and Mental Health
University of Newcastle
PO Box 833
Newcastle, NSW, 2300
Country 49478 0
Australia
Phone 49478 0
+61 2 40335715
Fax 49478 0
+61 2 4033 5692
Email 49478 0
[email protected]
Contact person for public queries
Name 49479 0
Alison Beck
Address 49479 0
Priority Research Centre for Translational Neuroscience and Mental Health
University of Newcastle
PO Box 833
Newcastle, NSW, 2300
Country 49479 0
Australia
Phone 49479 0
+61 2 40335039
Fax 49479 0
+61 2 4033 5692
Email 49479 0
[email protected]
Contact person for scientific queries
Name 49480 0
Benjamin Britton
Address 49480 0
Priority Research Centre for Translational Neuroscience and Mental Health
University of Newcastle
PO Box 833
Newcastle, NSW, 2300
Country 49480 0
Australia
Phone 49480 0
+61 2 40335715
Fax 49480 0
+61 2 4033 5692
Email 49480 0
[email protected]

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