<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03754140</url>
  </required_header>
  <id_info>
    <org_study_id>HREC/18/RPAH 621</org_study_id>
    <nct_id>NCT03754140</nct_id>
  </id_info>
  <brief_title>Intralesional Sclerosant for in Transit and Cutaneous Melanoma Metastases</brief_title>
  <acronym>INTRANS</acronym>
  <official_title>Intralesional Sclerosant for in Transit and Cutaneous Melanoma Metastases</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Melanoma Institute Australia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Melanoma Institute Australia</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      There is currently an urgent need for low cost and well tolerated intralesional agents for&#xD;
      the management of in transit and cutaneous melanoma metastases that are unsuitable for, or&#xD;
      resistant to, other therapies. This pilot study will determine whether intralesional&#xD;
      injections of the sclerosant polidocanol into intransit and cutaneous melanoma lesions shows&#xD;
      promise for efficacy, safety and ease of use that will enable this inexpensive and widely&#xD;
      available agent to undergo further evaluation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Many patients with metastatic melanoma have in transit and other cutaneous metastases.&#xD;
      Untreated, these lesions become eroded, haemorrhagic and symptomatic. When systemic therapy&#xD;
      is not warranted, has failed or is not tolerated for in transit disease, and when surgery is&#xD;
      not feasible or appropriate, other local treatments are needed. Current options include&#xD;
      isolated limb infusion for bulky limb disease, topical immunotherapy with contact sensitisers&#xD;
      and imiqiuimod for superficial, nonbulky disease or radiation therapy. Intralesional (IL)&#xD;
      agents such as Rose Bengal (PV-10, Provectus) and Talimogene laherparepvec (T-Vec, Amgen)&#xD;
      have been used for patients with limited numbers of cutaneous metastases with reported&#xD;
      overall response rates of 51% and 26% respectively. It is thought that these IL agents can&#xD;
      incite regional or even systemic anti-tumour immune responses, thus providing benefit beyond&#xD;
      the individual injected lesions. Use of PV-10, which is not an intrinsic immune modulator,&#xD;
      was associated with regression of untreated bystander lesions in 27% of patients.&#xD;
&#xD;
      T-Vec is not currently available as a subsidised product in Australia and PV-10 is not&#xD;
      currently accessible outside of dual-agent systemic/IL clinical trials. Intralesional&#xD;
      injection of the antimetabolites 5-fluorouracil and methotrexate has been used successfully&#xD;
      for the treatment of cutaneous squamous cell carcinoma, but the efficacy of these agents in&#xD;
      melanoma is unknown. Importantly, the investigator's in transit melanoma patients usually&#xD;
      have multiple, often very numerous lesions, making IL injection with adequate volumes of&#xD;
      antimetabolites difficult without significant risk of systemic haematologic, hepatic and&#xD;
      renal side effects.&#xD;
&#xD;
      Hence there is currently an urgent need for tolerable, low cost and accessible intralesional&#xD;
      therapies for in transit and cutaneous melanoma metastases.&#xD;
&#xD;
      This study aims to evaluate the efficacy and tolerability of intralesional therapy with the&#xD;
      sclerosant polidocanol for treatment of in transit and cutaneously metastatic melanoma&#xD;
      unsuitable for other therapies.&#xD;
&#xD;
      Intravascularly injected sclerosants have a long history of safe and effective use in the&#xD;
      treatment of varicose veins. Sclerosants have also been used intralesionally for the&#xD;
      treatment of cutaneous lesions such as squamous cell carcinoma, pyogenic granulomas, Kaposi&#xD;
      sarcoma and angiomas. They are inexpensive, readily accessible and can be easily administered&#xD;
      in the clinic to multiple metastases. By inciting cell death within melanoma metastases in&#xD;
      the skin, they may also incite anti-tumour immune responses in untreated bystander lesions,&#xD;
      as is observed with IL PV-10 therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Unable to identify eligible patients within planned timeframe&#xD;
  </why_stopped>
  <start_date type="Actual">May 20, 2020</start_date>
  <completion_date type="Anticipated">December 2022</completion_date>
  <primary_completion_date type="Anticipated">December 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Open label, single arm pilot study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical efficacy of interlesional polidocanol injection assessed by the size of in transit melanoma metastases after treatment</measure>
    <time_frame>8 weeks</time_frame>
    <description>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)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of treatment related adverse events</measure>
    <time_frame>8 weeks</time_frame>
    <description>Treatment related adverse events using the CTCAE version 4 terms and grading.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bystander treatment effect on untreated intransit melanoma metastases</measure>
    <time_frame>8 weeks</time_frame>
    <description>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)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bystander treatment effect on the proportion of tumour infiltrating immune markers in treated and untreated melanoma lesions</measure>
    <time_frame>8 weeks</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bystander treatment effect on tumour viabilty in treated and untreated melanoma lesions</measure>
    <time_frame>8 weeks</time_frame>
    <description>The proportion of residual non-necrotic melanoma cells detected histolologcally in treated and untreated lesions one week after intralesional injection.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Melanoma</condition>
  <condition>In-Transit Metastasis of Cutaneous Melanoma</condition>
  <arm_group>
    <arm_group_label>Polidocanol Injection</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Polidocanol (3%) 0.1ml intralesional injection per 10mm diameter lesion</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Polidocanol Injection</intervention_name>
    <description>Sclerotic agent</description>
    <arm_group_label>Polidocanol Injection</arm_group_label>
    <other_name>Aethoxysklerol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed in transit and/or cutaneous melanoma metastases unsuitable&#xD;
             for, or with progressive disease despite systemic, surgical, intra-arterial, topical&#xD;
             or radiation therapies&#xD;
&#xD;
          -  A minimum of 2 accessible lesions&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Periocular lesions&#xD;
&#xD;
          -  Severe renal impairment defined as an estimated glomerular filtration rate&#xD;
             &lt;20ml/min/1.73sqm&#xD;
&#xD;
          -  Sever liver function abnormality defined as aspartate aminotransferase and / or&#xD;
             alanine aminotransferase &gt; 3 x upper limit of normal and / or bilirubin &gt; 1.5 x upper&#xD;
             limit of normal&#xD;
&#xD;
          -  known hypersensitivity to polidocanol or its exipients&#xD;
&#xD;
          -  Patients unavailble for the full study duration (of a 4 week screening period and 8&#xD;
             week treatment period) because of general frailty, geographical or social reasons&#xD;
&#xD;
          -  Pregnant or breast feeding female patients&#xD;
&#xD;
          -  Patients receiving topical or radiation therapy to the in transit and / or cutaneous&#xD;
             lesions within 4 weeks of planned start of study treatment (patients receiving current&#xD;
             systemic immunotherapy which is deemed appropriate to continue, despite progression of&#xD;
             disease in the skin, in order to reduce the likelihood of visceral metastases are&#xD;
             eligible)&#xD;
&#xD;
          -  Patients receiving sclerosants for other indications within 4 weeks of planned start&#xD;
             of study treatment or during study treatment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Diona Damian</last_name>
    <role>Study Director</role>
    <affiliation>Royal Prince Alfred Hospital, Sydney, Australia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Royal Prince Alfred Hospital</name>
      <address>
        <city>Camperdown</city>
        <state>New South Wales</state>
        <zip>2050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>October 31, 2018</study_first_submitted>
  <study_first_submitted_qc>November 22, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 2018</study_first_posted>
  <last_update_submitted>July 12, 2022</last_update_submitted>
  <last_update_submitted_qc>July 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sclerosant</keyword>
  <keyword>Polidocanol</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</mesh_term>
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Skin Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polidocanol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03754140
org study id: HREC/18/RPAH 621
nct id: NCT03754140
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
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.
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.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Open label, single arm pilot study
primary purpose: Treatment
masking: None (Open Label)
measure: Clinical efficacy of interlesional polidocanol injection assessed by the size of in transit melanoma metastases after treatment
time frame: 8 weeks
description: 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)
measure: Incidence of treatment related adverse events
time frame: 8 weeks
description: Treatment related adverse events using the CTCAE version 4 terms and grading.
measure: Bystander treatment effect on untreated intransit melanoma metastases
time frame: 8 weeks
description: 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)
measure: Bystander treatment effect on the proportion of tumour infiltrating immune markers in treated and untreated melanoma lesions
time frame: 8 weeks
description: 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.
measure: Bystander treatment effect on tumour viabilty in treated and untreated melanoma lesions
time frame: 8 weeks
description: The proportion of residual non-necrotic melanoma cells detected histolologcally in treated and untreated lesions one week after intralesional injection.
arm group label: Polidocanol Injection
arm group type: Experimental
description: Polidocanol (3%) 0.1ml intralesional injection per 10mm diameter lesion
intervention type: Drug
intervention name: Polidocanol Injection
description: Sclerotic agent
arm group label: Polidocanol Injection
other name: Aethoxysklerol
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Diona Damian
role: Study Director
affiliation: Royal Prince Alfred Hospital, Sydney, Australia
facility: 
country: Australia
responsible party type: Sponsor
mesh term: Melanoma
mesh term: Neoplasm Metastasis
mesh term: Skin Neoplasms
mesh term: Polidocanol
sharing ipd: No