<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/NCT01723813</url>
  </required_header>
  <id_info>
    <org_study_id>LUC 10-001</org_study_id>
    <nct_id>NCT01723813</nct_id>
  </id_info>
  <brief_title>Peptide Vaccinations Plus GM-CT-01 in Melanoma</brief_title>
  <official_title>Phase I/II Study of Peptide Vaccination Associated With GM-CT-01, a Galactomannan Oligomer That Inhibits Galectin-3, in Patients With Advanced Metastatic Melanoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cliniques universitaires Saint-Luc- Université Catholique de Louvain</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cliniques universitaires Saint-Luc- Université Catholique de Louvain</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether the intravenous and/or GM-CT-01&#xD;
      administration can correct Tumor Infiltrating Lymphocytes (TIL) anergy and induce a more&#xD;
      efficient and long-lasting anti-tumoral immune response following peptide vaccination.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Human cancers express tumor antigens that can be targeted by cytolytic T lymphocytes (CTL).&#xD;
      These antigens consist of a small peptide, derived from endogenous proteins, that is&#xD;
      presented at the cancer cell's surface by an HLA class I molecule. Such antigenic peptides,&#xD;
      including MAGE-3.A1 and NA17.A2, have been tested in experimental therapeutic vaccines to&#xD;
      elicit CTL responses in cancer patients, mainly with metastatic melanoma. Up to now, only&#xD;
      rare tumor responses have been observed.&#xD;
&#xD;
      Tumor resistance to CTL killing is the most likely explanation for the poor effectiveness of&#xD;
      cancer vaccines. This resistance is probably acquired by the tumor during its development and&#xD;
      selected by its repetitive challenge with spontaneous anti-tumoral immune responses.&#xD;
      Recently, we have identified a novel mechanism causing anergy of tumor-associated T&#xD;
      lymphocytes, and established new approaches to correct this anergy in vitro. Galectin-3,&#xD;
      secreted by tumor cells, appears to inhibit CTL function the co-localization of the T cell&#xD;
      receptor and the cluster of differentiation 8 coreceptor. Importantly, this functional defect&#xD;
      is restored when anergic T cells are incubated with galectin-3 inhibitors such as the&#xD;
      disaccharides lactose and N-acetyllactosamine, and the polysaccharide GM-CT-01. GM-CT-01 is a&#xD;
      vegetal galactomannan oligomer, currently under clinical investigation in several types of&#xD;
      solid malignancies for its capacity to inhibit galectins and to synergize with chemotherapy&#xD;
      drugs.&#xD;
&#xD;
      Our observations suggest that treatment of cancer patients with GM-CT-01 could correct TIL&#xD;
      anergy and induce a more efficient and long-lasting anti-tumoral immune response following&#xD;
      peptide vaccination.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    due to end of validity of peptide vaccine&#xD;
  </why_stopped>
  <start_date>April 2012</start_date>
  <completion_date type="Actual">April 1, 2015</completion_date>
  <primary_completion_date type="Actual">April 1, 2015</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with adverse events</measure>
    <time_frame>30 days after last administration of Study drugs</time_frame>
    <description>Change from baseline in adverse events will be recorded at each patient's visit and up to 30 days after last administration of study drugs. Measurements will use the Common Toxicity Criteria for Adverse Effects 4,0 scale</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Response rate in both arms</measure>
    <time_frame>Change from baseline at week 7 and week 20</time_frame>
    <description>Efficacy of the combination of a peptide vaccine and GM-CT-01 injections measures performed by CT-scan or MRI</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Response rate in group 2 versus group 1</measure>
    <time_frame>Change from baseline at week 7 and week 20</time_frame>
    <description>To determine whether addition of peri-tumoral injections of GM-CT-01 increase tumor response therefore response rate observed in group 1 will be compared with group 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Progression</measure>
    <time_frame>From date of inclusion until the date of first documented progression or date of death from any cause, which ever came first, assessed up to 100 weeks</time_frame>
    <description>patients will be followed every three months at consultation and with radiological examination, they will be assessed up to 100 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>From day of inclusion to date of death</time_frame>
    <description>patients will be followed every three months at consultation and with radiological examination, they will be assessed up to 100 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity of the treatment</measure>
    <time_frame>Change from baseline at week 20</time_frame>
    <description>assessed at baseline and at week 20</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Translational research</measure>
    <time_frame>baseline and at progression</time_frame>
    <description>anti-tumoral immunological events in tumor samples obtained before and at progression</description>
  </other_outcome>
  <other_outcome>
    <measure>Pharmacokinetics of GM-CT-01</measure>
    <time_frame>Change from baseline at days 46 to 48</time_frame>
    <description>serum concentration of GM-CT-01</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Metastatic Melanoma</condition>
  <arm_group>
    <arm_group_label>Group 1 : peptides + GM-CT-01 IV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tumor specific peptides: MAGE-3.A1 and / or NA17.A2 plus Galectin-3 inhibitor: GM-CT-01 systemic injections</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2 : peptides + GM-CT-01 IV+PT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tumor specific peptides: MAGE-3.A1 and / or NA17.A2 plus Galectin-3 inhibitor: GM-CT-01 systemic injections and Galectin-3 inhibitor: GM-CT-01 Peri-tumoral administration</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Tumor specific peptides: MAGE-3.A1 and / or NA17.A2</intervention_name>
    <description>Each peptide will be given at a dose of 300 µg in 1 ml of sodium chloride 0.9%, every 3 weeks on 6 occasions, and will be administered at one site in arm or thigh, 20% of the dose intradermally and 80% of the dose subcutaneously.</description>
    <arm_group_label>Group 1 : peptides + GM-CT-01 IV</arm_group_label>
    <arm_group_label>Group 2 : peptides + GM-CT-01 IV+PT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Galectin-3 inhibitor: GM-CT-01 systemic injections</intervention_name>
    <description>Systemic injection of GM-CT-01: GM-CT-01 will be administered by slow intravenous infusions at a dose of 280 mg/m2, on days +3, +6, +9, +12, +15, +18 after each of the 3rd, 4th, 5th and 6th vaccination.</description>
    <arm_group_label>Group 1 : peptides + GM-CT-01 IV</arm_group_label>
    <arm_group_label>Group 2 : peptides + GM-CT-01 IV+PT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Galectin-3 inhibitor: GM-CT-01 Peri-tumoral administration</intervention_name>
    <description>GM-CT-01 will be injected peri-tumoral at a dose of 100 µg per tumor injected, on days +3, +6, +9, +12, +15, +18 after each of the 3rd, 4th, 5th and 6th vaccination. If a patient has one or two superficial metastases at day 43 of the treatment, one of these lesions will be treated. If a patient has more than two superficial metastases at day 43, two of these lesions will be treated.</description>
    <arm_group_label>Group 2 : peptides + GM-CT-01 IV+PT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with histologically proven cutaneous melanoma at one of the following&#xD;
             American Joint Committee on Cancer stages : Regional metastatic disease (any T; N2c or&#xD;
             N3; M0), no amenable to curative treatment by surgery or isolated limb&#xD;
             perfusion.Distant metastatic disease (any T; any N; M1a, M1b or M1c*).*except&#xD;
             uncontrolled brain metastasis and except Lactate dehydrogenase &gt;1.5 upper normal value&#xD;
&#xD;
          -  HLA-A1 or HLA-A2 (by serology or molecular biology)&#xD;
&#xD;
          -  At least one of the two following conditions:&#xD;
&#xD;
        MAGE-3 gene expression by the tumor if patient is HLA-A1 NA17 gene expression by the tumor&#xD;
        if patient is HLA-A2 (determined by reverse transcription and polymerase chain reaction&#xD;
        amplification).&#xD;
&#xD;
          -  Measurable Disease. Patients must have at least 1 measurable metastasis at study entry&#xD;
             for all patients. In addition, patients candidates for enrollment in Group 2 who will&#xD;
             receive peri-tumoral injections of GM-CT-01 must have at least 1 superficial&#xD;
             metastasis (cutaneous, subcutaneous or superficial lymph node metastasis, with its&#xD;
             largest diameter equal to or greater than 5, 5, or 10 mm, respectively) at study&#xD;
             entry.&#xD;
&#xD;
          -  Age ≥ 18 years.&#xD;
&#xD;
          -  Karnofsky Performance status ≥70 or WHO performance status of 0 or 1&#xD;
&#xD;
          -  Expected survival of at least 6 months.&#xD;
&#xD;
          -  Laboratory values :&#xD;
&#xD;
        Platelet count ≥100x103/μL Leukocyte count ≥ 3x103/μL Hemoglobin ≥ 9 g/dL Aspartate&#xD;
        transaminase and Alanine transaminase ≤ 2 times upper normal value Serum creatinine ≤1.5&#xD;
        times upper normal value Total bilirubin ≤ 1.5 times upper normal value Lactate&#xD;
        dehydrogenase ≤ 1.5 times upper normal value&#xD;
&#xD;
          -  Viral serology : negative antibodies for Hepatitis C Virus &amp; HIV; negative antigens&#xD;
             for Hepatitis B Virus.&#xD;
&#xD;
          -  Patient should agree to perform biopsies and blood collections for translational&#xD;
             research.&#xD;
&#xD;
          -  Signed informed consent from the patient must be obtained.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Uncontrolled brain or central nervous system metastasis.&#xD;
&#xD;
          -  Previous treatment for the melanoma within 6 weeks from inclusion, with any reagent&#xD;
             known to modulate the immune system such as a cancer vaccine, interferon-alpha,&#xD;
             interleukins or anti-CTLA-4 antibodies.&#xD;
&#xD;
          -  Previous chemotherapy, radiotherapy, corticotherapy, or other immune suppressive&#xD;
             therapy within 4 weeks from inclusion.&#xD;
&#xD;
          -  Clinically significant cardiovascular disease (including cardiac insufficiency New&#xD;
             York Heart Association grade III and IV, unstable angina, arrythmia, myocardial&#xD;
             infarction, symptomatic congestive heart failure) in the past 12 months before&#xD;
             enrollment.&#xD;
&#xD;
          -  Other serious acute or chronic illnesses, e.g. active infections requiring&#xD;
             antibiotics, bleeding disorders or other conditions requiring concurrent medications&#xD;
             not allowed during this study.&#xD;
&#xD;
          -  Other malignancy within 3 years prior to entry in the study, except for treated&#xD;
             non-melanoma skin cancer and in situ cervical carcinoma.&#xD;
&#xD;
          -  Active immunodeficiency disease or autoimmune disease (vitiligo is not an exclusion&#xD;
             criterion).&#xD;
&#xD;
          -  Lack of availability for immunological and clinical follow-up assessments.&#xD;
&#xD;
          -  Participation in any other clinical trial involving another investigational agent&#xD;
             within 4 weeks prior to enrollment.&#xD;
&#xD;
          -  Subject pregnant or breastfeeding, or planning to become pregnant within 6 months&#xD;
             after the end of treatment.&#xD;
&#xD;
          -  Subject (male or female) not willing to use highly effective methods of contraception&#xD;
             (per institutional standard) during treatment and for 6 months after the end of&#xD;
             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>Jean-Francois BAURAIN, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cliniques univeristaires Saint-Luc</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cliniques Universitaires Saint Luc</name>
      <address>
        <city>Brussels</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>September 28, 2012</study_first_submitted>
  <study_first_submitted_qc>November 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 8, 2012</study_first_posted>
  <last_update_submitted>March 8, 2019</last_update_submitted>
  <last_update_submitted_qc>March 8, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 12, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Immunotherapy</keyword>
  <keyword>Tumor-specific peptides</keyword>
  <keyword>GM-CT-01</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</mesh_term>
  </condition_browse>
  <!-- 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/NCT01723813
org study id: LUC 10-001
nct id: NCT01723813
lead sponsor: 
has dmc: No
The purpose of this study is to determine whether the intravenous and/or GM-CT-01
      administration can correct Tumor Infiltrating Lymphocytes (TIL) anergy and induce a more
      efficient and long-lasting anti-tumoral immune response following peptide vaccination.
Human cancers express tumor antigens that can be targeted by cytolytic T lymphocytes (CTL).
      These antigens consist of a small peptide, derived from endogenous proteins, that is
      presented at the cancer cell's surface by an HLA class I molecule. Such antigenic peptides,
      including MAGE-3.A1 and NA17.A2, have been tested in experimental therapeutic vaccines to
      elicit CTL responses in cancer patients, mainly with metastatic melanoma. Up to now, only
      rare tumor responses have been observed.

      Tumor resistance to CTL killing is the most likely explanation for the poor effectiveness of
      cancer vaccines. This resistance is probably acquired by the tumor during its development and
      selected by its repetitive challenge with spontaneous anti-tumoral immune responses.
      Recently, we have identified a novel mechanism causing anergy of tumor-associated T
      lymphocytes, and established new approaches to correct this anergy in vitro. Galectin-3,
      secreted by tumor cells, appears to inhibit CTL function the co-localization of the T cell
      receptor and the cluster of differentiation 8 coreceptor. Importantly, this functional defect
      is restored when anergic T cells are incubated with galectin-3 inhibitors such as the
      disaccharides lactose and N-acetyllactosamine, and the polysaccharide GM-CT-01. GM-CT-01 is a
      vegetal galactomannan oligomer, currently under clinical investigation in several types of
      solid malignancies for its capacity to inhibit galectins and to synergize with chemotherapy
      drugs.

      Our observations suggest that treatment of cancer patients with GM-CT-01 could correct TIL
      anergy and induce a more efficient and long-lasting anti-tumoral immune response following
      peptide vaccination.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with adverse events
time frame: 30 days after last administration of Study drugs
description: Change from baseline in adverse events will be recorded at each patient's visit and up to 30 days after last administration of study drugs. Measurements will use the Common Toxicity Criteria for Adverse Effects 4,0 scale
measure: Response rate in both arms
time frame: Change from baseline at week 7 and week 20
description: Efficacy of the combination of a peptide vaccine and GM-CT-01 injections measures performed by CT-scan or MRI
measure: Response rate in group 2 versus group 1
time frame: Change from baseline at week 7 and week 20
description: To determine whether addition of peri-tumoral injections of GM-CT-01 increase tumor response therefore response rate observed in group 1 will be compared with group 2
measure: Time to Progression
time frame: From date of inclusion until the date of first documented progression or date of death from any cause, which ever came first, assessed up to 100 weeks
description: patients will be followed every three months at consultation and with radiological examination, they will be assessed up to 100 weeks
measure: Overall Survival
time frame: From day of inclusion to date of death
description: patients will be followed every three months at consultation and with radiological examination, they will be assessed up to 100 weeks
measure: Immunogenicity of the treatment
time frame: Change from baseline at week 20
description: assessed at baseline and at week 20
measure: Translational research
time frame: baseline and at progression
description: anti-tumoral immunological events in tumor samples obtained before and at progression
measure: Pharmacokinetics of GM-CT-01
time frame: Change from baseline at days 46 to 48
description: serum concentration of GM-CT-01
arm group label: Group 1 : peptides + GM-CT-01 IV
arm group type: Experimental
description: Tumor specific peptides: MAGE-3.A1 and / or NA17.A2 plus Galectin-3 inhibitor: GM-CT-01 systemic injections
arm group label: Group 2 : peptides + GM-CT-01 IV+PT
arm group type: Experimental
description: Tumor specific peptides: MAGE-3.A1 and / or NA17.A2 plus Galectin-3 inhibitor: GM-CT-01 systemic injections and Galectin-3 inhibitor: GM-CT-01 Peri-tumoral administration
intervention type: Biological
intervention name: Tumor specific peptides: MAGE-3.A1 and / or NA17.A2
description: Each peptide will be given at a dose of 300 µg in 1 ml of sodium chloride 0.9%, every 3 weeks on 6 occasions, and will be administered at one site in arm or thigh, 20% of the dose intradermally and 80% of the dose subcutaneously.
arm group label: Group 1 : peptides + GM-CT-01 IV
arm group label: Group 2 : peptides + GM-CT-01 IV+PT
intervention type: Biological
intervention name: Galectin-3 inhibitor: GM-CT-01 systemic injections
description: Systemic injection of GM-CT-01: GM-CT-01 will be administered by slow intravenous infusions at a dose of 280 mg/m2, on days +3, +6, +9, +12, +15, +18 after each of the 3rd, 4th, 5th and 6th vaccination.
arm group label: Group 1 : peptides + GM-CT-01 IV
arm group label: Group 2 : peptides + GM-CT-01 IV+PT
intervention type: Biological
intervention name: Galectin-3 inhibitor: GM-CT-01 Peri-tumoral administration
description: GM-CT-01 will be injected peri-tumoral at a dose of 100 µg per tumor injected, on days +3, +6, +9, +12, +15, +18 after each of the 3rd, 4th, 5th and 6th vaccination. If a patient has one or two superficial metastases at day 43 of the treatment, one of these lesions will be treated. If a patient has more than two superficial metastases at day 43, two of these lesions will be treated.
arm group label: Group 2 : peptides + GM-CT-01 IV+PT
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jean-Francois BAURAIN, MD, PhD
role: Principal Investigator
affiliation: Cliniques univeristaires Saint-Luc
facility: 
country: Belgium
responsible party type: Sponsor
mesh term: Melanoma