MelanomaPhase 2INTRANSNCT03754140
Intralesional Sclerosant for in Transit and Cutaneous Melanoma Metastases
A Phase 2 study testing Polidocanol Injection in people with Melanoma and In-Transit Metastasis of Cutaneous Melanoma, run by Melanoma Institute Australia at 1 site in Australia.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma, In-Transit Metastasis of Cutaneous Melanoma
- What is being tested?
- Polidocanol Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteAustralia
- Study dates
- 20 May 2020to Dec 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Australia1 site
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050
About this study
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.
Read the 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.
- Being tested
- Polidocanol Injection
- Keywords
- Sclerosant, Polidocanol
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Polidocanol InjectionDrug
Also called Aethoxysklerol
Sclerotic agent
| Study group | Role | What they receive |
|---|---|---|
| Polidocanol Injection | Experimental | Polidocanol (3%) 0.1ml intralesional injection per 10mm diameter lesion Receives: Drug: Polidocanol Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical efficacy of interlesional polidocanol injection assessed by the size of in transit melanoma metastases after treatment
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)
Measured: 8 weeks
Secondary outcomes (4)
Incidence of treatment related adverse events
Treatment related adverse events using the CTCAE version 4 terms and grading.
Measured: 8 weeks
Bystander treatment effect on untreated intransit melanoma metastases
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)
Measured: 8 weeks
Bystander treatment effect on the proportion of tumour infiltrating immune markers in treated and untreated melanoma lesions
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.
Measured: 8 weeks
Bystander treatment effect on tumour viabilty in treated and untreated melanoma lesions
The proportion of residual non-necrotic melanoma cells detected histolologcally in treated and untreated lesions one week after intralesional injection.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2018
- Study start20 May 2020
- Primary completionDec 2022 (estimated)
- Study completionDec 2022 (estimated)
Why it stopped: Unable to identify eligible patients within planned timeframe
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open label, single arm pilot study
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Melanoma Institute Australia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Diona Damian, Study director, Royal Prince Alfred Hospital, Sydney, Australia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03754140
- Sponsor's protocol ID
- HREC/18/RPAH 621
- Acronym
- INTRANS
- Status last verified
- Jul 2022
- First submitted
- 31 Oct 2018
- Last updated
- 14 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intralesional Sclerosant for in Transit and Cutaneous Melanoma Metastases
- ClinicalTrials.gov ID
- NCT03754140
- Acronym / sponsor ID
- INTRANS / HREC/18/RPAH 621
- Keywords
- Sclerosant, Polidocanol
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Unable to identify eligible patients within planned timeframe
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Melanoma Institute AustraliaUniversity, hospital or other
- Study start
- 20 May 2020 (actual)
- Primary completion
- Dec 2022 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 27 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open label, single arm pilot study
| Arm | Type | Receives |
|---|---|---|
| Polidocanol Injection | Experimental | Drug: Polidocanol InjectionPolidocanol (3%) 0.1ml intralesional injection per 10mm diameter lesion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Polidocanol InjectionAlso: AethoxysklerolSclerotic agent | Drug | Polidocanol Injection |
Primary outcome
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)
4 secondary outcomes
Incidence of treatment related adverse events
Time frame: 8 weeks
Bystander treatment effect on untreated intransit melanoma metastases
Time frame: 8 weeks
Bystander treatment effect on the proportion of tumour infiltrating immune markers in treated and untreated melanoma lesions
Time frame: 8 weeks
Bystander treatment effect on tumour viabilty in treated and untreated melanoma lesions
Time frame: 8 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2022.
- Individual participant dataSharing planned: No
Related trials for Melanoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 1
A Feasibility Study Utilizing Immune Recall to Increase Response to Checkpoint Therapy
Melanoma
Active, not recruitingPhase 1/2
A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma
Melanoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Diona Damian study director
Royal Prince Alfred Hospital, Sydney, Australia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Polidocanol Injection in people with Melanoma and In-Transit Metastasis of Cutaneous Melanoma, run by Melanoma Institute Australia at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 14 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical efficacy of interlesional polidocanol injection assessed by the size of in transit melanoma metastases after treatment (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2022.