Intralesional Sclerosant for in Transit and Cutaneous Melanoma Metastases (INTRANS)

July 12, 2022 updated by: Melanoma Institute Australia
There is currently an urgent need for low cost and well tolerated intralesional agents for the management of in transit and cutaneous melanoma metastases that are unsuitable for, or resistant to, other therapies. This pilot study will determine whether intralesional injections of the sclerosant polidocanol into intransit and cutaneous melanoma lesions shows promise for efficacy, safety and ease of use that will enable this inexpensive and widely available agent to undergo further evaluation.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Royal Prince Alfred Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Polidocanol Injection
Polidocanol (3%) 0.1ml intralesional injection per 10mm diameter lesion
Drug: Polidocanol Injection
Sclerotic agent
Other Names:
  • Aethoxysklerol

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Melanoma Institute Australia

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Diona Damian, Royal Prince Alfred Hospital, Sydney, Australia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 20, 2020

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 31, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 22, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 27, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 14, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 12, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HREC/18/RPAH 621

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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.

Clinical Trials on Melanoma

Clinical Trials on Polidocanol Injection

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings