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Trial registered on ANZCTR


Registration number
ACTRN12620000656932p
Ethics application status
Submitted, not yet approved
Date submitted
21/04/2020
Date registered
5/06/2020
Date last updated
29/09/2020
Date data sharing statement initially provided
5/06/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Duloxetine and Pregabalin for Neuropathic Cancer Pain
Scientific title
A Phase III, international, multi-centre, double-blind, dose increment, parallel-arm, randomised controlled trial of duloxetine versus pregabalin over 14 days for opioid unresponsive cancer-related neuropathic pain.
Secondary ID [1] 301051 0
040/18
Universal Trial Number (UTN)
Trial acronym
DEPARTURE study
Linked study record
The Japanese parallel study is registered via the following link:

https://jrct.niph.go.jp/en-latest-detail/jRCTs051190097

Health condition
Health condition(s) or problem(s) studied:
Neuropathic Cancer Pain 317101 0
Cancer 317102 0
Condition category
Condition code
Anaesthesiology 315266 315266 0 0
Pain management
Cancer 315836 315836 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Duloxetine 30/day orally for 7 days, then increase to 60mg/day for 7 days, then downward titrate to 30mg/day for 7 days.
Total duration of treatment is 21 days, titrate up to maximal dose to primary endpoint at day 14, then downward titration to cease.
adherence will be monitored by review of daily dosing record completed by participant (at each contact), and reconciliation of returns.
Intervention code [1] 317354 0
Treatment: Drugs
Comparator / control treatment
Pregabalin 50/day orally for 3 days, 150mg/day for 4 days, then 300mg/day for 7 days, then downward titration to 150mg/day for 4 days, and 50mg/day for 3 days.
Total duration of treatment is 21 days, titrate up to maximal dose to primary endpoint at day 14, then downward titration to cease.
adherence will be monitored by review of daily dosing record completed by participant (at each contact), and reconciliation of returns.
Control group
Active

Outcomes
Primary outcome [1] 323507 0
Primary outcome is to compare the worst pain intensity (BPI item 3)
Timepoint [1] 323507 0
Day 14
Secondary outcome [1] 382093 0
The average pain intensity (BPI items 5)
Timepoint [1] 382093 0
Day 14 and 21
Secondary outcome [2] 382094 0
The worst pain intensity (BPI items 3)
Timepoint [2] 382094 0
Day 21
Secondary outcome [3] 382095 0
The short-form McGill Pain Questionnaire 2 (SF-MPQ-2 scores)
Timepoint [3] 382095 0
Day 14
Secondary outcome [4] 382096 0
European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C15-PAL
Timepoint [4] 382096 0
Day 14
Secondary outcome [5] 382097 0
The Hospital Anxiety and Depression Scale (HADS)
Timepoint [5] 382097 0
Day 14
Secondary outcome [6] 382098 0
Daily opioid dose using a participant completed daily diary of dosing and medications.
Timepoint [6] 382098 0
Daily to day 21
Secondary outcome [7] 382099 0
Toxicity assessment (NCI CTCAE; Nausea, Light-headedness, Sleepiness, Oedema/PRO-AE)
Timepoint [7] 382099 0
Day 14 and 21
Secondary outcome [8] 382100 0
Percentage of participants with a reduction (BPI-I items 3) decrease from the baseline
Timepoint [8] 382100 0
Days 3, 7 and 21.
Secondary outcome [9] 382101 0
Health service utilization- including planned and unplanned contact, investigations, hospitalisations. Recorded via participant report of health service use.
Timepoint [9] 382101 0
Day 14 and 21

Eligibility
Key inclusion criteria
Inpatients and outpatients with diagnoses of cancer and neuropathic pain (probable or definite neuropathic pain by IASP criteria).
Age 18 years or more.
KPS or AKPS 50 or greater.
Able to complete study assessments and comply with the study procedures.
Ability to provide informed written consent.
Pain related to cancer with a worst pain score of 4 or greater on BPI item 3 (worst pain intensity) score in the past 24 hours.
Neuropathic Pain on LANSS 12 or greater.
An adequate opioid medication (clinical assessment participant is currently taking an adequate opioid medication)
Taking stable regular analgesics within 72 hours before commencing on the study.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Chemotherapy-Induced Peripheral Neuropathy (glove and stocking).
Spinal cord compression.
Contraindication for duloxetine or pregabalin.
Taking gabapentioids or duloxetine for any reason within 2 weeks.
Taking SSRI or SNRI for any reason.
Taking reversible monoamine oxidase inhibitors (MAOIs)
Depressive symptomology or suicidality (HADS depression subscale greater than or equal to 16)
Participants who have participated in a clinical trial involving a new chemical entity within four weeks prior to study entry.
Patients with clinically significant cognitive impairment (clinician defined) causing unreliable completion of study procedures.
Patients who have a current or recent history of abuse of alcohol, or recent history of substance misuse..
Patients who are pregnant, breastfeeding or may possibly be pregnant.
Other patients who are determined to be inappropriate for participation in the study by the clinical investigator.
Starting a new chemotherapy regimen within 14 days of baseline .
Patients with renal failure defined as eGFR less than 30ml/min/1.73m2 calculated according to the MDRD formula.
Patients with hepatic failure (Child Pugh B or C).

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)
All medicine packs will be prepared by the site clinical trial pharmacist (unblinded) according to the randomisation schedule. Treatment allocation will not be disclosed to study staff, treating clinicians or investigators. The code will only be broken in cases of extreme emergency. Such situations only include where knowledge of the treatment allocation will have consequences for clinical decision making in consultation with the Lead Chief Investigator.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The REDCap randomisation tool will be used to facilitate randomisation. Treatment for each participant will be allocated in a 1:1 ratio. Randomisation will be done with minimization method, with 6 allocation factors; Race (Australian (Asian descent; e.g; China, India, Vietnam, Phillippines, etc), Australian (partial or no Asian descent), Japanese, others (e.g; Italy South, Africa, etc)), Body weight (greater than or equal to 80kg or less than 80kg), Dose of Opioid (greater than or equal to 90mg oral morphine equivalent dose, 60-90mg, <60mg), NRS score (greater than or equal to 7, less than or equal to 6 ), HADS score (greater than or equal to 11, less than or equal to 10), and sites.
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
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Comparison of the primary endpoint of the worst pain intensity (BPI item 3) at Day 14 between the duloxetine group and the pregabalin group will be conducted using a two-sided Student’s t-test at a significance level of 5% according to the intention-to-treat principle. Point estimates and 95% Confidence Intervals (Cis) for the difference between the two group means will be calculated. The handling of missing values and the necessity for a sensitivity analysis will be outlined in detail in a separate statistical analysis.

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,QLD,VIC
Recruitment hospital [1] 16483 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 16484 0
Mater Adult Hospital - South Brisbane
Recruitment hospital [3] 16485 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 30033 0
2170 - Liverpool
Recruitment postcode(s) [2] 30034 0
4101 - South Brisbane
Recruitment postcode(s) [3] 30035 0
3050 - Parkville

Funding & Sponsors
Funding source category [1] 305493 0
Government body
Name [1] 305493 0
NHMRC
Address [1] 305493 0
16 Marcus Clarke St,
Canberra ACT 2601
Country [1] 305493 0
Australia
Primary sponsor type
University
Name
University of Technology Sydney
Address
15 Broadway
Ultimo NSW 2007
Country
Australia
Secondary sponsor category [1] 305891 0
None
Name [1] 305891 0
Address [1] 305891 0
Country [1] 305891 0
Other collaborator category [1] 281290 0
Other Collaborative groups
Name [1] 281290 0
Japanese Organisation for Research and Treatment of Cancer
Address [1] 281290 0
3 Chome-4-1 Kowakae, Higashiosaka, Osaka 577-8502, Japan
Country [1] 281290 0
Japan

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 305805 0
South Western Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 305805 0
Research Directorate
Locked Bag 7103
LIVERPOOL BC NSW 1871
Ethics committee country [1] 305805 0
Australia
Date submitted for ethics approval [1] 305805 0
01/05/2020
Approval date [1] 305805 0
Ethics approval number [1] 305805 0

Summary
Brief summary
This study aims to evaluate the effectiveness and safety of duloxetine and pregabalin for neuropathic cancer pain.

Who is it for?
You may be eligible to join this study if you are aged 18 years or above, and have a diagnosis of cancer and neuropathic pain.

Study details
Participants in this study will be randomly allocated (by chance) to one of two groups. Participants in one group will take an oral dose of the drug, Duloxetine, once daily for 14 days. Participants in the other group will take daily oral pregabalin instead.

All participants will be monitored for safety, and toxicity. They will also be asked to complete questionnaires to rate their cancer pain, quality of life, anxiety and depression for up to 21 days. It is hoped that this comparison of benefits and harms between duloxetine and pregabalin will help us to better treat people with neuropathic cancer pain.
Trial website
None
Trial related presentations / publications
None
Public notes

Contacts
Principal investigator
Name 101658 0
Prof Katherine Clark
Address 101658 0
Faculty of Health|The University of Technology (Sydney)
Northern Sydney Cancer Centre Royal North Shore Hospital
Reserve Rd
St Leonards
NSW
2065
Country 101658 0
Australia
Phone 101658 0
+61 2 9463 1200
Fax 101658 0
Email 101658 0
Katherine.Clark@health.nsw.gov.au
Contact person for public queries
Name 101659 0
Prof Katherine Clark
Address 101659 0
Faculty of Health|The University of Technology (Sydney)
Northern Sydney Cancer Centre Royal North Shore Hospital
Reserve Rd
St Leonards
NSW
2065
Country 101659 0
Australia
Phone 101659 0
+61 2 9463 1200
Fax 101659 0
Email 101659 0
Katherine.Clark@health.nsw.gov.au
Contact person for scientific queries
Name 101660 0
Prof Katherine Clark
Address 101660 0
Faculty of Health|The University of Technology (Sydney)
Northern Sydney Cancer Centre Royal North Shore Hospital
Reserve Rd
St Leonards
NSW
2065
Country 101660 0
Australia
Phone 101660 0
+61 2 9463 1200
Fax 101660 0
Email 101660 0
Katherine.Clark@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data that underlie the results reported in the article(s) after deidentification and other documents (study protocol and statistical analysis plan) will be available for any purpose, only if approved by JORTC Independent Data Monitoring Committee (IDMC) and the PaCCSC Scientific Committee.
When will data be available (start and end dates)?
Twelve months after the publication of the primary results and only if approved by JORTC Independent Data Monitoring Committee (IDMC) and the PaCCSC Scientific Committee.
The end date is not specified.
Available to whom?
Anyone who wishes to access the data to bon fide researchers
Available for what types of analyses?
Any purpose.
How or where can data be obtained?
Anyone who wishes to access the data should submit a proposal to office@idmc.jortc.jp.
If approved, data requestors will need to sign a data access agreement.
After that, JORTC Data Center will transfer the data and other documents to data requestors.
What supporting documents are/will be available?
No other documents available
Summary results
No Results