- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03754140
Intralesional Sclerosant for in Transit and Cutaneous Melanoma Metastases (INTRANS)
Study Overview
Status
Intervention / Treatment
Detailed Description
Many patients with metastatic melanoma have in transit and other cutaneous metastases. Untreated, these lesions become eroded, haemorrhagic and symptomatic. When systemic therapy is not warranted, has failed or is not tolerated for in transit disease, and when surgery is not feasible or appropriate, other local treatments are needed. Current options include isolated limb infusion for bulky limb disease, topical immunotherapy with contact sensitisers and imiqiuimod for superficial, nonbulky disease or radiation therapy. Intralesional (IL) agents such as Rose Bengal (PV-10, Provectus) and Talimogene laherparepvec (T-Vec, Amgen) have been used for patients with limited numbers of cutaneous metastases with reported overall response rates of 51% and 26% respectively. It is thought that these IL agents can incite regional or even systemic anti-tumour immune responses, thus providing benefit beyond the individual injected lesions. Use of PV-10, which is not an intrinsic immune modulator, was associated with regression of untreated bystander lesions in 27% of patients.
T-Vec is not currently available as a subsidised product in Australia and PV-10 is not currently accessible outside of dual-agent systemic/IL clinical trials. Intralesional injection of the antimetabolites 5-fluorouracil and methotrexate has been used successfully for the treatment of cutaneous squamous cell carcinoma, but the efficacy of these agents in melanoma is unknown. Importantly, the investigator's in transit melanoma patients usually have multiple, often very numerous lesions, making IL injection with adequate volumes of antimetabolites difficult without significant risk of systemic haematologic, hepatic and renal side effects.
Hence there is currently an urgent need for tolerable, low cost and accessible intralesional therapies for in transit and cutaneous melanoma metastases.
This study aims to evaluate the efficacy and tolerability of intralesional therapy with the sclerosant polidocanol for treatment of in transit and cutaneously metastatic melanoma unsuitable for other therapies.
Intravascularly injected sclerosants have a long history of safe and effective use in the treatment of varicose veins. Sclerosants have also been used intralesionally for the treatment of cutaneous lesions such as squamous cell carcinoma, pyogenic granulomas, Kaposi sarcoma and angiomas. They are inexpensive, readily accessible and can be easily administered in the clinic to multiple metastases. By inciting cell death within melanoma metastases in the skin, they may also incite anti-tumour immune responses in untreated bystander lesions, as is observed with IL PV-10 therapy.
Study Type
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
New South Wales
-
Camperdown, New South Wales, Australia, 2050
- Royal Prince Alfred Hospital
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologically confirmed in transit and/or cutaneous melanoma metastases unsuitable for, or with progressive disease despite systemic, surgical, intra-arterial, topical or radiation therapies
- A minimum of 2 accessible lesions
Exclusion Criteria:
- Periocular lesions
- Severe renal impairment defined as an estimated glomerular filtration rate <20ml/min/1.73sqm
- Sever liver function abnormality defined as aspartate aminotransferase and / or alanine aminotransferase > 3 x upper limit of normal and / or bilirubin > 1.5 x upper limit of normal
- known hypersensitivity to polidocanol or its exipients
- Patients unavailble for the full study duration (of a 4 week screening period and 8 week treatment period) because of general frailty, geographical or social reasons
- Pregnant or breast feeding female patients
- Patients receiving topical or radiation therapy to the in transit and / or cutaneous lesions within 4 weeks of planned start of study treatment (patients receiving current systemic immunotherapy which is deemed appropriate to continue, despite progression of disease in the skin, in order to reduce the likelihood of visceral metastases are eligible)
- Patients receiving sclerosants for other indications within 4 weeks of planned start of study treatment or during study treatment.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Polidocanol Injection
Polidocanol (3%) 0.1ml intralesional injection per 10mm diameter lesion
|
Sclerotic agent
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical efficacy of interlesional polidocanol injection assessed by the size of in transit melanoma metastases after treatment
Time Frame: 8 weeks
|
Proportion of patients with a complete response (complete disappearance of treated lesions), partial response (a 25% or more reduction in size of treated lesions), stable disease (a 0 to 24% reduction in size of treated lesions) or disease progression (any increase in size of treated lesions)
|
8 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of treatment related adverse events
Time Frame: 8 weeks
|
Treatment related adverse events using the CTCAE version 4 terms and grading.
|
8 weeks
|
Bystander treatment effect on untreated intransit melanoma metastases
Time Frame: 8 weeks
|
Proportion of patients with a complete response (complete disappearance of untreated lesions), partial response (a 25% or more reduction in size of untreated lesions), stable disease (a 0 to 24% reduction in size of untreated lesions) or disease progression (any increase in size of untreated lesions)
|
8 weeks
|
Bystander treatment effect on the proportion of tumour infiltrating immune markers in treated and untreated melanoma lesions
Time Frame: 8 weeks
|
The proportion (%) of tumour-infiltrating immune markers: CD4, CD8 and FoxP3 T cell markers, CD20 (B cell), CD16 and CD56 Natural Killer (NK) cell markers, Ki67 marker of proliferation, CD31 (endothelial cells) and CD68 and CD163 (macrophages) detected at baseline and 1 week after intralesional injection by immunohistochemistry.
The same analysis will be undertaken in a minimuim of one untreated lesion detected at baseline and at anytime between 1 and 8 weeks.
Change in the proportion (%) of immune markers will be ,made within each lesion and between each lesion.
|
8 weeks
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Bystander treatment effect on tumour viabilty in treated and untreated melanoma lesions
Time Frame: 8 weeks
|
The proportion of residual non-necrotic melanoma cells detected histolologcally in treated and untreated lesions one week after intralesional injection.
|
8 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Diona Damian, Royal Prince Alfred Hospital, Sydney, Australia
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Skin Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neoplastic Processes
- Neuroendocrine Tumors
- Nevi and Melanomas
- Neoplasm Metastasis
- Melanoma
- Skin Neoplasms
- Pharmaceutical Solutions
- Sclerosing Solutions
- Polidocanol
Other Study ID Numbers
- HREC/18/RPAH 621
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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