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Trial registered on ANZCTR


Registration number
ACTRN12618000951257
Ethics application status
Approved
Date submitted
1/06/2018
Date registered
6/06/2018
Date last updated
16/11/2018
Date data sharing statement initially provided
16/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Assessment of Radiotherapy in the management of Dupuytren’s Disease
Scientific title
DEPART: Dupuytren’s disease Evaluation of Preventative or Adjuvant Radiation Therapy
Secondary ID [1] 295068 0
None
Universal Trial Number (UTN)
U1111-1215-0612
Trial acronym
DEPART
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dupuytren’s Disease 308113 0
Condition category
Condition code
Inflammatory and Immune System 307153 307153 0 0
Connective tissue diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Currently, treatment for early phase Dupuytren’s Disease is observation and in the later phase of the condition, treatment is surgery. As a randomised controlled trial, treatment will be allocated as follows:
- Preventative Therapy: Observation or Radiation Therapy
- Adjuvant Therapy: Surgery or Surgery and Radiation Therapy

Radiotherapy will be targeted to the affected hand and over a split course. More specifically, 5 fractions of Radiation Therapy in one week, then 5 again after a 4-12 week break. This will be a total of 30Gy in 10 Fractions.
Intervention code [1] 301398 0
Treatment: Other
Intervention code [2] 301420 0
Prevention
Comparator / control treatment
In the early stages of Dupuytren’s Disease, observation is the standard of care, whereby physicians will monitor any progression and symptoms which may occur. In the later stages of the condition however, surgery is an option. Both these factors, in the different cohorts will be used as a comparison.
Control group
Active

Outcomes
Primary outcome [1] 306118 0
Primary Endpoint is Disease Progression, defined as increase of 20 degree flexion contraction in joint(s) of an affected hand (prevention) or treated digit(s) (adjuvant) OR instigation of salvage surgery to the affected hand within 5 years of study entry
Timepoint [1] 306118 0
Baseline, 4, 12, 24, 42 and 60 months post treatment
Secondary outcome [1] 347610 0
Toxicities will be measured. This will be graded as per CTCAE v4 grade 0-5 and includes:
a. Arthralgia – A disorder characterised by a marked sensation of discomfort in a joint
b. Dry Skin - A disorder characterized by flaky and dull skin; the pores are generally fine, the texture is a papery thin texture.
c. Fat Atrophy - A disorder characterized by shrinking of adipose tissue.
d. Hypohidrosis - A disorder characterized by reduced sweating.
e. Nail loss - A disorder characterized by loss of all or a portion of the nail.
f. Pain of Skin - A disorder characterized by marked discomfort sensation in the skin.
g. Palmar erythema – A disorder characterised by redness, marked discomfort, swelling, and tingling in the palms of the hands or the soles of the feet.
h. Pruritus - A disorder characterized by an intense itching sensation.
i. Skin atrophy - A disorder characterized by the degeneration and thinning of the epidermis and dermis.
j. Skin induration - A disorder characterized by an area of hardness in the skin.
k. Subsequent malignancy – A new cancer diagnosis, not including non-melanomatous skin cancers (cutaneous basal or squamous cell carcinomas)
Timepoint [1] 347610 0
Baseline, 4, 12, 24, 42 and 60 months post treatment
Secondary outcome [2] 347611 0
Compare patient reported pain outcomes using the Visual Analogue Scale (VAS 0-10) for radiotherapy verses observation. Any differences between arms and over time to be reported
Timepoint [2] 347611 0
Baseline, 4, 12, 24, 42 and 60 months post treatment
Secondary outcome [3] 347612 0
Disease activity as assessed by surface mapping
Timepoint [3] 347612 0
Baseline, 4, 12, 24, 42 and 60 months post treatment
Secondary outcome [4] 347706 0
Compare patient reported functional outcomes using the URAM (total score) for Dupuytren's Disease an QuickDASH (total score). Any differences between arms and over time to be reported
Timepoint [4] 347706 0
Baseline, 4, 12, 24, 42 and 60 months post treatment

Eligibility
Key inclusion criteria
Eligibility – All groups
Patient consent
Life expectancy >5 years
Available and willing to participate in 5 years of follow-up

Eligibility - Prevention
Evidence of nodules and/or cords in the affected hand consistent with DD
History of progressive DD over previous 6 months
Maximum flexion contracture of 10 degrees in the affected hand
Patients with progressive DD in both hands are potentially eligible. Each hand will be randomized separately.

Eligibility - Adjuvant
Planned for local treatment with Surgical Fasciectomy (SF), Needle Aponeurotomy (NA) or Collagenase Injection (CI) of flexion contracture(s)
Multiple digits on the same hand can be managed with local treatment. They will be randomized as a group to radiotherapy or observation.
Lack of intervention major acute complications and hand position achieved making it possible to deliver radiotherapy (note that this can only be assessed after the local treatment has been performed)
Minimum age
30 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Previous radiotherapy in the affected hand/s
Previous surgery in the affected hand/s
History of radiation sensitivity diseases (eg Scleroderma, Ataxia Telangiectasia, Li Fraumeni)
Pregnant patients

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 concealment is ensured by separating the role of inserting the randomization sequence into the generating spreadsheet to an individual not otherwise involved with the trial.. The randomization sequence will be hidden in a password protected manner from the staff involved in the trial enrolment process
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization is via a computer generated sequence, with the 4 groups as stratification factors
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Four inter-related randomized controlled trials of radiotherapy verses observation in the management of Dupuytren’s Disease .
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Prevention:
The rate of disease progression in an observational cohort with a minimum 5 years of follow up varies depending on the series. Using our definition of disease progression, it would appear that a progression rate of approximately 25% at 5 years is a reasonable estimate for the observational group. Using this estimate, we aim to demonstrate a halving of recurrence (HR=0.5) with preventative radiotherapy at the 5% significance level with a power of 80% assuming a dropout rate of 5% and a crossover rate of 5%, which will require 372 patients (186 per arm).
Adjuvant:
The recurrence rates in the literature are difficult to interpret. The UK National Institute for Health and Clinical Excellence (NICE) released their latest assessment of CI in July 2017. This included an attempt to estimate recurrence rates based on a definition of 20 degree joint flexion deterioration at 5 years combining both a midpoint of published estimates from a literature review as well as expert opinion. They concluded that a reasonable estimate for relapse for each of the 3 local treatment modalities was:
• SF – 25%
• NA – 52.5%
• CI – 42.8%
Using these estimates, we aim to demonstrate a halving of recurrence (HR=0.5) with adjuvant radiotherapy at the 5% significance level with a power of 80% assuming a dropout rate of 5% and a crossover rate of 5%

SF Adjuvant: 372 patients (186 per arm)
NA Adjuvant: 168 patients (84 per arm)
CI Adjuvant: 208 patients (104 per arm)

Recruitment
Recruitment status
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] 11056 0
Genesis Cancer Care - Gateshead
Recruitment postcode(s) [1] 22858 0
2290 - Gateshead

Funding & Sponsors
Funding source category [1] 299650 0
Commercial sector/Industry
Name [1] 299650 0
Cancer Care Research Pty Limited
Address [1] 299650 0
Building 1&11, The Mill, 41-43 Bourke Road, Alexandria NSW 2015
Country [1] 299650 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Genesis Care
Address
Building 1&11, The Mill, 41-43 Bourke Road, Alexandria NSW 2015
Country
Australia
Secondary sponsor category [1] 298979 0
None
Name [1] 298979 0
Address [1] 298979 0
Country [1] 298979 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300548 0
Bellberry Human Research Ethics Committee G
Ethics committee address [1] 300548 0
129 Glen Osmond Road Eastwood South Australia 5063
Ethics committee country [1] 300548 0
Australia
Date submitted for ethics approval [1] 300548 0
08/06/2018
Approval date [1] 300548 0
18/07/2018
Ethics approval number [1] 300548 0

Summary
Brief summary
This trial will assess patients with Dupuytren’s Disease in two settings: those who have early stages of the disease, and those who have progressive flexion contractures. It is the first trial of its kind and aims to assess safety and efficacy in the use of radiotherapy in both settings.

We hypothesise that radiotherapy reduces the incidence of disease progression in people with Dupuytren’s Disease managed in the early stages with a policy of observation, or in the later stages following local treatment in the form of SF, NA or CI.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 84022 0
Dr Jarad Martin
Address 84022 0
GenesisCare
Lake Macquarie Private Hospital
36 Pacific Highway GATESHEAD NSW 2290
Country 84022 0
Australia
Phone 84022 0
+61249184500
Fax 84022 0
Email 84022 0
Jarad.Martin@genesiscare.com.au
Contact person for public queries
Name 84023 0
Ms Amanda Janus
Address 84023 0
GenesisCare
Lake Macquarie Private Hospital
36 Pacific Highway
Gateshead NSW 2290
Country 84023 0
Australia
Phone 84023 0
+61 2 4918 4500
Fax 84023 0
Email 84023 0
amanda.janus@genesiscare.com
Contact person for scientific queries
Name 84024 0
Ms Amanda Janus
Address 84024 0
GenesisCare
Lake Macquarie Private Hospital
36 Pacific Highway
Gateshead NSW 2290
Country 84024 0
Australia
Phone 84024 0
+61 2 4918 4500
Fax 84024 0
Email 84024 0
amanda.janus@genesiscare.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
will review and confirm
What supporting documents are/will be available?
Informed consent form
Summary results
No Results