ANZCTR - Registration

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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]

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

Condition category

Condition code

Neurological

Other neurological disorders

Cancer

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]

Treatment: Drugs

Comparator / control treatment

Placebo: lactose capsules for eight weeks.

Control group

Placebo

Outcomes

Primary outcome [1]

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]

Baseline, and at 4 and 8 weeks after intervention commencement.

Secondary outcome [1]

Total Neuropathy Score (TNS)

Timepoint [1]

Baseline, and at 8 weeks after intervention commencement.

Secondary outcome [2]

Grooved pegboard test

Timepoint [2]

Baseline, and at 8 weeks after intervention commencement.

Secondary outcome [3]

Brief Pain Inventory Short Form (BPI-SF)

Timepoint [3]

Baseline, and at 8 weeks after intervention commencement.

Secondary outcome [4]

Hospital Anxiety and Depression Scale (HADS)

Timepoint [4]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Prince of Wales Hospital - Randwick

Recruitment hospital [2]

Sydney Adventist Hospital - Wahroonga

Recruitment postcode(s) [1]

2031 - Randwick

Recruitment postcode(s) [2]

2076 - Wahroonga

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

Cancer Institute NSW

Address [1]

Level 9, 8 Central Avenue
Australian Technology Park
Eveleigh NSW 2015

Country [1]

Australia

Primary sponsor type

Hospital

Name

Prince of Wales Hospital

Address

Barker St
Randwick NSW 2031

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

SESLHD HREC

Ethics committee address [1]

Research Support Office
G71, East Wing 
Edmund Blacket Building
Prince of Wales Hospital
Randwick NSW 2031

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

06/05/2016

Approval date [1]

11/08/2016

Ethics approval number [1]

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

Dr Susanna Park

Address

Prince of Wales Clinical School
Level 4, Lowy Cancer Research Centre
University of New South Wales
Sydney NSW 2052

Country

Australia

Phone

+61468326975

Fax

N/A

s.park@neura.edu.au

Contact person for public queries

Name

Eva Battaglini

Address

Prince of Wales Clinical School
Level 4, Lowy Cancer Research Centre
University of New South Wales
Sydney NSW 2052

Country

Australia

Phone

+61293858204

Fax

N/A

in_focus@unsw.edu.au

Contact person for scientific queries

Name

Eva Battaglini

Address

Prince of Wales Clinical School
Level 4, Lowy Cancer Research Centre
University of New South Wales
Sydney NSW 2052

Country

Australia

Phone

+61293858204

Fax

N/A

in_focus@unsw.edu.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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.	Type	Citation	Link	Email	Other Details	Attachment
5748	Study protocol	Battaglini 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: 135-138	https://www.sciencedirect.com/science/article/pii/S1551714418300569?via%3Dihub

Results publications and other study-related documents

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No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

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