Trial Review

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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
23/02/2024
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: Needle Aponeurotomy (NA) followed by observation or NA followed by Radiation Therapy. Note: Adjuvant therapy is determined at the discretion of the Clinician and patient decision.

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:
- Prevention Group: Measurement of 20 degrees, or greater, PED in joint(s) of
an affected hand OR instigation of salvage SF or NA to the affected hand or
- Adjuvant Groups: Deterioration greater than 20 degrees PED in any joint(s)
of any of the affected digit(s) from post-intervention baseline in the presence
of a palpable cord OR instigation of salvage SF or NA to any of the affected
digit(s).
Timepoint [1] 306118 0
Baseline, 6, 12, 24, 36, 48 and 60, 84 and 108 months post treatment
Secondary outcome [1] 347610 0
Toxicities will be measured. This will be graded as per CTCAE v4.03 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, 6, 12, 24, 36, 48 and 60, 84 and 108 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, 6, 12, 24, 36, 48 and 60, 84 and 108 months post treatment
Secondary outcome [3] 347612 0
Disease activity as assessed by surface mapping (this is an optional substudy for sites which have access to surface mapping equipment).
Timepoint [3] 347612 0
Baseline, 6, 12, 24, 36, 48 and 60, 84 and 108 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, 6, 12, 24, 36, 48 and 60, 84 and 108 months post treatment

Eligibility
Key inclusion criteria
Eligibility – All groups - (Prevention and Adjuvant)
- Patient consent
- No previous radiotherapy to the affected hand
- No history of radiation sensitivity diseases (eg Scleroderma, Ataxia Telangiectasia, Li
Fraumeni)
- Age>30
- Life expectancy >5 years
- Available and willing to participate in at least 5 years of follow-up
- Female patients capable of child-bearing are not pregnant

Eligibility – Prevention Arm
- Evidence of nodules and/or cords in the affected hand consistent with DD.
- History of progressive DD over previous 6 months.
- No previous SF, NA or CI in the affected hand.
- Absence of flexion contractures: PED must be less than, or equal to, 10 degrees in any joints of the affected hand.

Eligibility – Adjuvant Arm
- Local treatment with Needle Aponeurotomy (NA) of flexion
contracture(s) performed within 6-12 weeks prior to post-intervention baseline
measurements
- Lack of major acute complications due to surgical intervention and less than or equal to 20 degrees PED in all joints of affected rays and less than or equal to 10 degrees PED in remaining joints in the affected hand
- Able to commence radiotherapy treatment within 12 weeks of local treatment with Needle Aponeurotomy (NA).
Minimum age
30 Years
Maximum age
No limit
Sex
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 3 groups as stratification factors
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Three 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. The control group of 122 hands in the Seegenschmiedt study had a 30% risk of progression to a contraction requiring surgical intervention. A 59 patient American series reported 10 patients (17%) requiring surgery over 8.5 years follow-up for a mixture of symptomatic nodules or relatively advanced contractures (average 60 degrees at the metacarpophalangeal joint). An Icelandic series showed that 34.6% of 75 men with nodules or cords at initial assessment either had developed contractures or been operated on after 18 years of follow-up. The varying definitions of progression, ethnic backgrounds and duration of follow-up make it challenging to reconcile these data. 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 an almost halving of recurrence (HR=0.565).
There shall be an interim analysis for efficacy at the half-way point of the study. The settings for the sample size calculation were as follows. It shall be assumed that the time to disease progression follows an exponential distribution. The accrual period was assumed to be 48 months with 108 months of maximum follow up. For the observation arm disease progression rate was 25% at 60 months which equates to a median of 144.6 months. For the treated arm the corresponding disease progression rate was 15.0% at 60 months which equates to a median of 255.9 months. The hazard ratio equals 0.565. The level of significance was set to 0.05 with a 2-sided test, and required 80% power. For these settings the required sample size was 182 per arm, so 364 in total. The sample size will be increased to 205 per arm, so 410 in total to allow for early withdrawals. The power of 80% is achieved with 97 observed events for the final analysis. The interim analysis requires the enrolment of 91 patients per arm with 49 events in total. At the interim analysis the study would
stop for efficacy if the observed p-value was less than 0.003. At the final analysis significance would be declared if the p-value was less than 0.047.

Adjuvant:
The recurrence rates in the literature are difficult to interpret due to several factors:
- Differing definitions of relapse (eg 20-degree flexion, 30-degree flexion, rate of re-intervention)
- Series having different rates of recurrent disease at the time of study entry
- Mixed prospective and retrospective experiences
- Effect of mastery of new technology leading to improving outcomes, especially with the
diffusion of CI as a standard treatment approach.

Reasonable estimates for relapse at 5 years consistent with the current definition of progression (protocol v3.1) for each of the 3 local treatment modalities was:
- SF – 20.9%(11)
- NA – 84.9%(11)
- CI – 47%(18)

Collagenase was removed due to being no longer available on the market. SF was removed due to funding constraints and limited recruitment potential.
NA sample size - 158 hands (79 per arm)

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/07/2018
Actual
10/08/2018
Date of last participant enrolment
Anticipated
31/12/2024
Actual
Date of last data collection
Anticipated
31/12/2033
Actual
Sample size
Target
568
Accrual to date
417
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 11056 0
Genesis Cancer Care - Gateshead
Recruitment postcode(s) [1] 35861 0
2137 - Concord
Recruitment postcode(s) [2] 35862 0
2220 - Hurstville
Recruitment postcode(s) [3] 22858 0
2290 - Gateshead
Recruitment postcode(s) [4] 35865 0
3199 - Frankston
Recruitment postcode(s) [5] 35864 0
5000 - Adelaide
Recruitment postcode(s) [6] 35863 0
5022 - Tennyson
Recruitment outside Australia
Country [1] 25666 0
Netherlands
State/province [1] 25666 0
Groningen

Funding & Sponsors
Funding source category [1] 299650 0
Commercial sector/Industry
Name [1] 299650 0
Cancer Care Research Pty Limited
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
2018-02-134

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 NA.
Trial website
https://www.genesiscare.com/au/clinical-trials/connective-tissue-disorders/
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 84022 0
Prof 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
Mrs Rebecca Nathan
Address 84023 0
GenesisCare
Building 7C & D,
Level 1, The Mill,
41-43 Bourke Road
Alexandria NSW 2015
Country 84023 0
Australia
Phone 84023 0
+61 429777325
Fax 84023 0
Email 84023 0
GC-Depart@genesiscare.com
Contact person for scientific queries
Name 84024 0
Mrs Rebecca Nathan
Address 84024 0
GenesisCare
Building 7C & D,
Level 1, The Mill,
41-43 Bourke Road
Alexandria NSW 2015
Country 84024 0
Australia
Phone 84024 0
+61 429777325
Fax 84024 0
Email 84024 0
GC-Depart@genesiscare.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Participant consent does not allow for sharing of IPD


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.