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Trial registered on ANZCTR


Registration number
ACTRN12615001088538
Ethics application status
Approved
Date submitted
14/09/2015
Date registered
16/10/2015
Date last updated
26/11/2018
Date data sharing statement initially provided
26/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Topical Imiquimod or Diphenylcyclopropenone for the Management of Cutaneous In-transit Melanoma Metastases – A Phase II Single Centre Prospective Randomised Pilot Study
Scientific title
The effect of topical imiquimod or diphenylcyclopropenone on complete clinical response in patients with cutaneous in-transit melanoma metastases - A Phase II Single Centre Prospective Randomised Pilot Study.
Secondary ID [1] 287337 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Topical Imiquimod or Diphenylcyclopropenone for Advanced Loco-regional Melanoma (TIDAL Melanoma) Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cutaneous in-transit melanoma metastases 295980 0
Condition category
Condition code
Cancer 296261 296261 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The investigational agents are diphenylcyclopropenone (DPCP) and imiquimod, two dermatological immunotherapies for topical administration to cutaneous in-transit lesions. Each agent will be administered topically with a 5mm peripheral margin to uniformly treat between 5-20 target lesions over a minimum of 12 months or until complete clinical resolution of loco-regional disease.

Treatment Arm A – 5% Topical Imiquimod Cream: Self-application 5 times weekly, regular clinical review, time to best response and formal 12 month assessment, regular clinical surveillance for duration of remaining trial.

Treatment Arm B – Topical DPCP Cream: Sensitisation with 2% solution then treatment using 0.005% solution - titrated to effect to a maximum of 5% , Responders commence treatment regimen - self-application once weekly, regular clinical review, titration to effect, time to best response and formal 12 month assessment, regular clinical surveillance for duration of remaining trial.

During the scheduled clinical review participants' records of dates (treatment log) of medication self-administration will be used to monitor adherence.
Intervention code [1] 292671 0
Treatment: Drugs
Comparator / control treatment
Historical control. Following completion of the TIDAL Melanoma Study a comparison to retrospective data will be made for patients treated with isolated limb infusion and PV-10 treatments. These modalities represent the existing standard of care at our institution. Data for these control treatments were derived from institutional records between 1996 - 2014.

PV-10 treatment involves an intra-lesional injection of Rose Bengal solution into in-transit melanoma metastases and has been investigated as a part of another phase II trial completed at our centre. For the formal treatment results of this investigation please refer to: Thompson JF, et al. Phase 2 Study of Intralesional PV-10 in Refractory Metastatic Melanoma. Ann Surg Oncol. 2014.

Isolated limb infusion involves isolating the vascular supply to a limb affected by in-transit melanoma metastases and instilling a loco regional chemotherapeutic agent, melphalan. For the formal institutional treatment results of from therapy please refer to: Barbour AP, et al. Isolated Limb Infusion for Malignant Melanoma: Predictors of Response and Outcome. Ann Surg Oncol. 2009.
Control group
Historical

Outcomes
Primary outcome [1] 295927 0
Complete clinical response in treated lesions assessed using standardised measurement tools (e.g. callipers) in accordance with Response Evaluation Criteria In Solid Tumors (RECIST).
Timepoint [1] 295927 0
Time to complete clinical response up to a maximum of 12 months after commencing treatment.
Secondary outcome [1] 316940 0
Length of time patients experience local disease/progression free survival assessed using standardised measurement tools (e.g. callipers) in accordance with RECIST..
Timepoint [1] 316940 0
Time to loco-regional disease progression with a maximum follow-up duration of 24 months after commencing treatment.
Secondary outcome [2] 316941 0
Melanoma-specific patient reported outcomes measured using the validated FACT-M quality of life sub-scale.
Timepoint [2] 316941 0
3, 6, 12, 18, 24 months
Secondary outcome [3] 316942 0
Overall survival length and rate.
Timepoint [3] 316942 0
Time to death up to a maximum of 24 months follow-up after commencing treatment or at the close of trial.
Secondary outcome [4] 316943 0
Proportions of patients experiencing complete response and partial response (overall response), stable disease and local disease progression as a composite secondary outcome. This will be achieved through regular clinical assessment of treated lesions (applying RECIST) and monitoring regional lymph nodes.
Timepoint [4] 316943 0
12, 18 and 24 months.
Secondary outcome [5] 316944 0
Patients experiencing overall disease progression including death following the completion of the treatment / complete clinical response. This will be achieved through regular clinical assessment of treated lesions (applying RECIST), monitoring regional lymph nodes and radiologically evaluating for distant disease using standardised investigations such as CT/PET scanning.
Timepoint [5] 316944 0
Time to disease progression (including death) assessed at 12, 18 and 24 months.
Secondary outcome [6] 316945 0
Estimated difference in the health-related costs between imiquimod or DPCP versus ILI or PV-10 through a comparison of health-related costs.
Timepoint [6] 316945 0
12 months following the commencement of treatment.
Secondary outcome [7] 317685 0
Time to best response in treated lesions assessed using standardised measurement tools (e.g. callipers) in accordance with RECIST.
Timepoint [7] 317685 0
Prior to or at 12 months follow-up.

Eligibility
Key inclusion criteria
1. Men or women aged 18 years or older.
2. Willing and able to comply with study requirements.
3. Capable of providing valid (written and informed) consent.
4. Histologically or cytologically proven in-transit melanoma metastases.
5. Measurable disease between 2-15mm in diameter that can be accurately assessed by ruler/calliper.
6. Between 5 to 20 in-transit melanoma lesions.
7. Lesions present in anatomical locations amenable to imiquimod or DPCP treatment.
8. Cutaneous (superficial) macular, papular or small nodular in-transit melanoma deposits.
9. Considered un-suitable for surgery by the treating surgeon due to anatomical location or prohibitive disease factors or co-morbidities, previous treatment failure or patient refusal.
10. 12 weeks minimum duration between completing comparative treatments (ILI or PV-10) to prevent potentially confounding effects (treatment responses).
11. Patients must have, in the opinion of the investigator, adequate renal, haematopoietic and hepatic function, with no clinically significant impairment or uncontrolled haematological, hepatic or renal disease.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Considered eligible for concurrent treatment with systemic chemo- or immunotherapies.
2. Subjects who have received chemotherapy or other systemic cancer therapy within 4 weeks of study.
3. Subjects who have received local treatment (e.g. surgery, cryotherapy, radiofrequency ablation) to the treatment area within four weeks of study treatment - to prevent potentially confounding effects (treatment responses/immunosuppression).
4. Life expectancy of less than 6 months or ECOG performance status equal or greater than 3.
5. Medical or psychiatric condition that compromises the patient’s ability to complete the treatment or follow-up assessments as per the protocol.
6. Unable or unwilling to provide fully informed consent and participate including patients with intellectual or mental impairment.
7. Patients who are pregnant or lactating. Women of child bearing potential must have a confirmed negative urine pregnancy test at study entry.
8. Known history of immumodeficiency including HIV, uncontrolled central nervous system metastases, concomitant systemic corticosteroid therapy, previous organ transplant.
9. Known severe concurrent or inter-current illness including: cardiovascular, respiratory or immunological) illness, psychiatric disorders, or alcohol or chemical dependence that would, in the opinion of the Investigator, compromise their safety or compliance or interfere with interpretation of study results.
10. Previous severe adverse or allergic reaction to either treatment agent.
11. Patients unable or unwilling to comply with home application of treatment and the investigational nature of the study.

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 of treatment will be performed centrally via an online randomisation system.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients will be randomised in a 1:1 ratio.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
All subjects who are enrolled and receive either treatment modality will be evaluated for efficacy, safety and progression-free survival with an intention to treat analysis.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/02/2016
Actual
6/01/2017
Date of last participant enrolment
Anticipated
3/02/2020
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
4
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 4263 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 10203 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 291904 0
Hospital
Name [1] 291904 0
Princess Alexandra Hospital - Queensland Health
Country [1] 291904 0
Australia
Primary sponsor type
Individual
Name
Professor B Mark Smithers
Address
Queensland Melanoma Project
Princess Alexandra Hospital
199 Ipswich Road
Woolloongabba
QLD 4102
Country
Australia
Secondary sponsor category [1] 290572 0
None
Name [1] 290572 0
Address [1] 290572 0
Country [1] 290572 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293411 0
Metro South HHS HREC - Queensland Health
Ethics committee address [1] 293411 0
Centres for Health Research
Level 7, Translational Research Institute Building
Princess Alexandra Hospital
Ipswich Road, Woolloongabba Qld 4102
Ethics committee country [1] 293411 0
Australia
Date submitted for ethics approval [1] 293411 0
17/09/2015
Approval date [1] 293411 0
10/11/2015
Ethics approval number [1] 293411 0
HREC/15/QPAH/632

Summary
Brief summary
Study Details
This study aims to compare two different non-invasive topical immunotherapies in patients with multiple, in-transit, cutaneous melanoma metastases. The hypothesis is that these treatments are at least as clinically effective as current therapies for patients with selective in-transit melanoma metastases and can be used to enhance patients’ quality of life and decrease health-related costs.

Who is it for?
You may be eligible to join this study if you are aged 18 years or older and have been diagnosed with histologically or cytologically proven in-transit melanoma metastases, which are considered unsuitable for surgery.

Intervention Description
Participants in this study will be randomly allocated (by chance) to one of two groups. Participants in one group will be given imiquimod cream and asked to apply it to their lesions five times weekly for up to 12 months. Participants in the other group will be given diphenylcyclopropenone (DPCP) cream instead, and asked to apply it to their lesions once weekly for up to 12 months. All participants will undergo regular clinical review with measurement of the treated lesions and assessment of their lymph nodes, routine blood tests and CT/PET scans, in order to evaluate the response to treatment. Patients will also be asked to complete a questionnaire evaluating quality of life at 3, 6, 12, and 18 months.

Study Outcomes
The results of this study may lead to improved patient rated outcomes compared to current strategies through a reduction in the burden of local disease, fewer serious treatment-related complications, more convenient application, streamlined review and ultimately decreased healthcare-associated expenditure.
Trial website
Trial related presentations / publications
Public notes
Patients will be assessed and treated through the Melanoma Specialist Outpatient Clinic at the Princess Alexandra Hospital, Brisbane. Access to two novel, topical immunotherapies will be provided without charge to eligible patients and will involve ongoing, multi-disciplinary care from dermatologists, plastic and reconstructive surgeons, general surgeons, oncologists and nursing specialists.

Contacts
Principal investigator
Name 59774 0
Prof B. Mark Smithers
Address 59774 0
Queensland Melanoma Project
Princess Alexandra Hospital
199 Ipswich Road
Woolloongabba
Queensland, 4102
Country 59774 0
Australia
Phone 59774 0
+61731767578
Fax 59774 0
+61731765399
Email 59774 0
[email protected]
Contact person for public queries
Name 59775 0
Janine Thomas
Address 59775 0
Queensland Melanoma Project
Princess Alexandra Hospital
199 Ipswich Road
Woolloongabba
Queensland, 4102
Country 59775 0
Australia
Phone 59775 0
+61731767578
Fax 59775 0
+61731765399
Email 59775 0
[email protected]
Contact person for scientific queries
Name 59776 0
B Mark Smithers
Address 59776 0
Queensland Melanoma Project
Princess Alexandra Hospital
199 Ipswich Road
Woolloongabba
Queensland, 4102
Country 59776 0
Australia
Phone 59776 0
+61 731762111
Fax 59776 0
+61731765399
Email 59776 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
IPD will be maintained confidentially by the responsible persons within the trial committee as approved by the appropriate HREC.


What supporting documents are/will be available?




Results publications and other study-related documents

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

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseProtocol for the TIDAL Melanoma Study: Topical imiquimod or diphenylcyclopropenone for the management of cutaneous in-transit melanoma metastases - A phase II, single centre, randomised, pilot study.2017https://dx.doi.org/10.1136/bmjopen-2017-016816
N.B. These documents automatically identified may not have been verified by the study sponsor.