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Trial registered on ANZCTR


Registration number
ACTRN12617000139370
Ethics application status
Approved
Date submitted
5/01/2017
Date registered
25/01/2017
Date last updated
19/11/2019
Date data sharing statement initially provided
11/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The use of duloxetine for the treatment of chemotherapy-induced peripheral neuropathy
Scientific title
The use of duloxetine for the treatment of chemotherapy-induced peripheral neuropathy
Secondary ID [1] 290822 0
Nil
Universal Trial Number (UTN)
U1111-1191-2794
Trial acronym
IN FOCUS trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chemotherapy-induced peripheral neuropathy 301490 0
Condition category
Condition code
Neurological 301357 301357 0 0
Other neurological disorders
Cancer 301358 301358 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Duloxetine will be administered for eight weeks via oral capsules. Participants will receive 30mg duloxetine per day for the first week of the active arm of the trial, uptitrating to 60mg for the following six weeks. Participants will then receive 30mg duloxetine for the final week of the active arm. There will be a two week wash-out period before crossover to the second study arm.

Adherence will be monitored via capsule counts at each study visit. Participants will also be asked whether they have missed any doses during weekly monitoring phone calls. If a participant reports missing doses, strategies for remembering to take the study medication (e.g. taking the study medication with meals, using reminder notes) will be suggested.
Intervention code [1] 296744 0
Treatment: Drugs
Comparator / control treatment
Placebo: lactose capsules for eight weeks.
Control group
Placebo

Outcomes
Primary outcome [1] 300620 0
Self-reported neuropathic symptom scores on the FACT/GOG-NTx neurotoxicity subscale. A difference of 2.8 points on this measure will be considered to be a clinically significant difference.
Timepoint [1] 300620 0
Baseline, and at 4 and 8 weeks after intervention commencement.
Secondary outcome [1] 330422 0
Total Neuropathy Score (TNS)
Timepoint [1] 330422 0
Baseline, and at 8 weeks after intervention commencement.
Secondary outcome [2] 330423 0
Grooved pegboard test
Timepoint [2] 330423 0
Baseline, and at 8 weeks after intervention commencement.
Secondary outcome [3] 330424 0
Brief Pain Inventory Short Form (BPI-SF)
Timepoint [3] 330424 0
Baseline, and at 8 weeks after intervention commencement.
Secondary outcome [4] 330425 0
Hospital Anxiety and Depression Scale (HADS)
Timepoint [4] 330425 0
Baseline, and at 8 weeks after intervention commencement.

Eligibility
Key inclusion criteria
1. Daily symptoms of peripheral neuropathy for at least 3 months after completing chemotherapy.
2. History of neuropathic symptoms beginning in extremities following chemotherapy, e.g.: dysesthesia, burning pain, hyperalgesia of lower extremities, shooting or lancinating pain, aching, or tingling.
3. At least grade 1 sensory neuropathy via the National Cancer Institute Common Terminology Criteria for Adverse Effects (NCI CTCAE) version 4.
4. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
5. Willingness and ability to give written informed consent, and willingness to participate in and comply with the study.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Currently receiving chemotherapy, or have received chemotherapy within the last 3 months.
2. Inability to speak English.
3. Pregnancy or lactation. Contraception is required in pre-menopausal female patients.
4. Calculated creatinine clearance less than 60 mL/min.
5. AST (aspartate aminotransferase) greater than or equal to 3 times upper limit of normal (greater than or equal to 135 U/L).
6. Total bilirubin greater than 25 umol/L.
7. INR (international normalised ratio) greater than 1.4.
8. Diabetes mellitus, type 1 and 2.
9. HIV infection.
10. Significant degenerative or familial neurologic disorder known to cause peripheral neuropathy.
11. Currently receiving active treatment for glaucoma.
12. Severe depression, suicidality, bipolar disorder, schizophrenia, major eating disorder, at the discretion of the treating clinician.
13. Alcohol abuse or dependence.
14. Current use of any class of antidepressant or antipsychotic medication. At least 14 days must have passed since last use of antidepressant medication. Medication should not have been discontinued without medical consultation.
15. Current use of CYP1A2 inhibitors, including:
- fluvoxamine
- ciprofloxacin
- enoxacin
- fluoroquinolones
- verapramil
- vemurafenib
- amiodarone
- interferon
- artemisinin
- atazanavir
16. Current use of anticoagulants.
17. Current treatment for peripheral neuropathy or neuropathic pain. Any treatments for these conditions must be ceased at least 14 days prior to randomisation.

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 will be concealed by the use of central randomisation via telephone/email.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will use permuted blocks (incorporating stratification via type of chemotherapy received by the patient).
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 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size calculations were conducted using a = 0.05 (two-tailed), and 80% power, aiming to detect a difference of 2.8 points on the FACT/GOG-NTx, equivalent to an effect size of 0.408. In order to achieve this effect size, and assuming a correlation of 0.6 within patient between periods on FACT/GOG-NTx scores, a sample size of 40 would have at least 80% power to detect these differences on the primary endpoint. Assuming a drop out rate similar to previous trials of duloxetine in CIPN, sample size will be adjusted by 20%, resulting in a total sample size of 48. Data for the primary endpoint will be compared via paired t-tests within patients. Comparisons between conditions will be undertaken using analysis of covariance with the baseline measure included as a covariate.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
20/02/2017
Actual
18/09/2017
Date of last participant enrolment
Anticipated
1/05/2020
Actual
Date of last data collection
Anticipated
1/09/2020
Actual
Sample size
Target
48
Accrual to date
10
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 7180 0
Prince of Wales Hospital - Randwick
Recruitment hospital [2] 15184 0
Sydney Adventist Hospital - Wahroonga
Recruitment postcode(s) [1] 14942 0
2031 - Randwick
Recruitment postcode(s) [2] 28494 0
2076 - Wahroonga

Funding & Sponsors
Funding source category [1] 295248 0
Government body
Name [1] 295248 0
Cancer Institute NSW
Country [1] 295248 0
Australia
Primary sponsor type
Hospital
Name
Prince of Wales Hospital
Address
Barker St
Randwick NSW 2031
Country
Australia
Secondary sponsor category [1] 294085 0
None
Name [1] 294085 0
Address [1] 294085 0
Country [1] 294085 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296587 0
SESLHD HREC
Ethics committee address [1] 296587 0
Research Support Office
G71, East Wing
Edmund Blacket Building
Prince of Wales Hospital
Randwick NSW 2031
Ethics committee country [1] 296587 0
Australia
Date submitted for ethics approval [1] 296587 0
06/05/2016
Approval date [1] 296587 0
11/08/2016
Ethics approval number [1] 296587 0
HREC ref: 16/150 (HREC/16/POWH/334)

Summary
Brief summary
This trial aims to assess whether treatment with duloxetine results in a reduction in chronic neuropathic symptoms experienced as a result of neurotoxic chemotherapy treatment.

Who is it for?
You may be eligible to join this study if you are aged 18 years or above, and have had daily symptoms of peripheral neuropathy for at least 3 months after completing chemotherapy.

Study details
Participants in this study will be randomly allocated (by chance) to receive the drug duloxetine or placebo (inactive treatment) for 8 weeks. After a two week washout period, participants will switch conditions and receive placebo or study drug for another eight weeks. Those allocated to the study drug arm will be started on duloxetine 30 mg once daily, increasing to 60mg daily for weeks 2-7, and back to 30mg daily for week 8. Participants randomised to the control group will receive a daily placebo capsule to the dosage matching the treatment arm. Placebo tablets will look identical to duloxetine, and participants will not know which treatment they are receiving. All participants in the trial will receive duloxetine for 8 weeks.

All participants will have liver and kidney function tests performed at baseline and at monthly intervals. Clinical examination, nerve conduction and excitability studies, functional assessment (nine-hole peg test) and self-report measures will be undertaken at baseline and after each 8 week treatment period. Patients will be asked to keep a symptom diary, which will be checked at each study visit.
Trial website
http://www.infocusstudy.org.au/drugtrial/
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 71382 0
Dr Susanna Park
Address 71382 0
Prince of Wales Clinical School
Level 4, Lowy Cancer Research Centre
University of New South Wales
Sydney NSW 2052
Country 71382 0
Australia
Phone 71382 0
+61468326975
Fax 71382 0
N/A
Email 71382 0
[email protected]
Contact person for public queries
Name 71383 0
Eva Battaglini
Address 71383 0
Prince of Wales Clinical School
Level 4, Lowy Cancer Research Centre
University of New South Wales
Sydney NSW 2052
Country 71383 0
Australia
Phone 71383 0
+61293858204
Fax 71383 0
N/A
Email 71383 0
[email protected]
Contact person for scientific queries
Name 71384 0
Eva Battaglini
Address 71384 0
Prince of Wales Clinical School
Level 4, Lowy Cancer Research Centre
University of New South Wales
Sydney NSW 2052
Country 71384 0
Australia
Phone 71384 0
+61293858204
Fax 71384 0
N/A
Email 71384 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
The ethics application for this trial allows for publication of aggregate patient data only.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
5748Study protocolBattaglini E, Park SB, Barnes EH, Goldstein D. (2018). A double blind, placebo controlled, phase II randomised cross-over trial investigating the use of duloxetine for the treatment of chemotherapy-induced peripheral neuropathy. Contemporary Clinical Trials. 70: 135-138https://www.sciencedirect.com/science/article/pii/S1551714418300569?via%3Dihub 



Results publications and other study-related documents

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