<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/NCT02994771</url>
  </required_header>
  <id_info>
    <org_study_id>CL12001</org_study_id>
    <nct_id>NCT02994771</nct_id>
  </id_info>
  <brief_title>A Phase I Study With Lymfactin® in the Treatment of Patients With Secondary Lymphedema</brief_title>
  <official_title>A Phase I Open-Label Study to Assess the Safety, Tolerability and Preliminary Efficacy of Lymfactin® (AdAptVEGF-C Adenoviral Vector) in Combination With a Surgical Lymph Node Transfer for the Treatment of Patients With Secondary Lymphedema</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Herantis Pharma Plc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Herantis Pharma Plc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Indicated for the Treatment of Secondary Lymphedema Associated with the Treatment of Breast&#xD;
      Cancer.&#xD;
&#xD;
      Primary objective is to evaluate the safety and tolerability of a single dose of Lymfactin®&#xD;
      in patients with secondary lymphedema associated with the treatment of breast cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open label, multi-center, uncontrolled first in human trial that uses a standard 3&#xD;
      + 3 dose escalation scheme. Lymfactin® will be administered as a single dose by ex vivo&#xD;
      perinodal injection into the fat pad of a flap of tissue containing lymph nodes from the&#xD;
      abdominal wall. This flap of tissue will then be surgically implanted into the axillary&#xD;
      region of the affected arm. This treatment with Lymfactin® may be performed in conjunction&#xD;
      with or without breast reconstruction surgery.&#xD;
&#xD;
      Up to two dose cohorts are planned to be included. Each dose of Lymfactin® will be&#xD;
      administered as a single dose via perinodal injection in a volume of 2 mL:&#xD;
&#xD;
        -  Cohort 1: Lymfactin® [1 x 10E10 vp]&#xD;
&#xD;
        -  Cohort 2: Lymfactin® [1 x 10E11 vp]&#xD;
&#xD;
      Should the dose escalation go up to Cohort 2 with initiation of a subsequent Extension Cohort&#xD;
      a total of 15 - 21 patients may be treated in this study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Lack of efficacy&#xD;
  </why_stopped>
  <start_date type="Actual">June 2016</start_date>
  <completion_date type="Actual">April 5, 2022</completion_date>
  <primary_completion_date type="Actual">February 3, 2019</primary_completion_date>
  <phase>Phase 1</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>Safety as measured by number of patients with treatment related adverse events and serious adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>baseline to 1 year, yearly up to 5 years</time_frame>
    <description>Adverse events and serious adverse events assessed by CTCAE v4.0 to evaluate the safety profile after administration of Lymfactin</description>
  </primary_outcome>
  <primary_outcome>
    <measure>CT scan of chest and abdomen</measure>
    <time_frame>baseline, yearly up to 5 years</time_frame>
    <description>Changes in the CT scan of chest and abdomen in order to detect malignancies</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Biodistribution of Lymfactin in blood</measure>
    <time_frame>90 days</time_frame>
    <description>Changes in Lymfactin genome copy number in blood</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Formation of anti-Lymfactin antibodies</measure>
    <time_frame>6 months</time_frame>
    <description>Changes in the anti-Lymfactin antibody titer in blood</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Measurement of the volume of the arms</measure>
    <time_frame>baseline, 6, 12, 24 and 36 months</time_frame>
    <description>Changes in the volume of the affected arm and comparison to the unaffected arm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measurement of the lymphatic flow of the affected arm by quantitative lymphoscintigraphy (99Tc-nanocolloid clearance rate with calculation of transport index)</measure>
    <time_frame>baseline, 12, 24 and 36 months</time_frame>
    <description>Assessment of the changes in the lymphatic flow</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Questionnaire according to the Lymphedema Quality of Life Inventory (LQOLI)</measure>
    <time_frame>baseline, 6, 12, 24 and 36 months</time_frame>
    <description>Assessment of changes in the quality of life using Lymphedema Quality of Life Inventory (LQOLI) in which patients assess how their lymphedema is affecting the activities of daily living. LQOLI consists of three dimensions: Physical, psychosocial and practical, which are reported separately as the mean score of each dimension. Each dimension of the LQOLI is scored from 0 to 3, where score 0 means &quot;no impact&quot;, 1 means &quot;a little bit impact&quot;, 2 means &quot;somewhat impact&quot;, and 3 means &quot;significant impact&quot; on the quality of life of the patient, the smaller score thus being the better.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Secondary Lymphedema</condition>
  <arm_group>
    <arm_group_label>Lymfactin® [1 x 10E10 vp]</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Lymfactin® [1 x 10E10 vp] will be administered as a single dose via perinodal injection in a volume of 2 mL.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lymfactin® [1 x 10E11 vp]</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Lymfactin® [1 x 10E11 vp] will be administered as a single dose via perinodal injection in a volume of 2 mL.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lymfactin® [1 x 10E10 vp]</intervention_name>
    <description>Lymfactin® [1 x 10E10 vp] will be administered as a single dose via perinodal injection in a volume of 2 mL.</description>
    <arm_group_label>Lymfactin® [1 x 10E10 vp]</arm_group_label>
    <other_name>LX-1101, AdAptVEGF-C Adenoviral Vector</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lymfactin® [1 x 10E11 vp]</intervention_name>
    <description>Lymfactin® [1 x 10E11 vp] will be administered as a single dose via perinodal injection in a volume of 2 mL.</description>
    <arm_group_label>Lymfactin® [1 x 10E11 vp]</arm_group_label>
    <other_name>LX-1101, AdAptVEGF-C Adenoviral Vector</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. Female patients with secondary lymphedema associated with the treatment of breast&#xD;
             cancer.&#xD;
&#xD;
          2. Patient who understands and voluntarily signs informed consent prior to any screening&#xD;
             procedure.&#xD;
&#xD;
          3. 18 - 70 years of age.&#xD;
&#xD;
          4. BMI between 18 and 32 inclusive.&#xD;
&#xD;
          5. Female patients with secondary lymphedema in the arm associated with breast cancer&#xD;
             who:&#xD;
&#xD;
               1. Have undergone sentinel lymph node biopsies and/or lymph node resection in the&#xD;
                  axilla on the affected side of their breast cancer with initial N1 staging and&#xD;
                  lymph node metastasis in ≤ three lymph nodes.&#xD;
&#xD;
               2. Require garment use as a compression treatment for the lymphedema in the affected&#xD;
                  arm.&#xD;
&#xD;
               3. Have the volume of the affected arm at least 10% greater than the unaffected arm&#xD;
                  following 7 days after removal of the compression garments.&#xD;
&#xD;
               4. Have the presence of pitting edema in the affected arm without compression&#xD;
                  garments.&#xD;
&#xD;
          6. No evidence of recurrent or active breast cancer at least 2 years and no more than 5&#xD;
             years after breast cancer surgery and/or the end of chemotherapy and/or radiotherapy&#xD;
             (excluding endocrine and/or aromatase inhibitor treatment). PET CT scan of the chest&#xD;
             and the abdomen within 45 days of treatment with Lymfactin® without signs of active&#xD;
             breast cancer or any other malignancy.&#xD;
&#xD;
          7. Patient with the following laboratory values:&#xD;
&#xD;
               1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times&#xD;
                  the institutional upper limit of normal (ULN)&#xD;
&#xD;
               2. Bilirubin ≤ 1.5 mg/dL&#xD;
&#xD;
               3. PT and PTT ≤ 1.5 times the ULN&#xD;
&#xD;
               4. Serum creatinine ≤ 2 mg/dL&#xD;
&#xD;
               5. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm³&#xD;
&#xD;
               6. Platelet count ≥ 100,000/mm³&#xD;
&#xD;
               7. Hemoglobin ≥ 10 g/dL&#xD;
&#xD;
          8. Willingness to comply with scheduled visits, laboratory assessments, and other&#xD;
             study-related procedures due to the regulatory requirements related to gene based&#xD;
             therapies.&#xD;
&#xD;
          9. Non-smoker or willing to stop smoking or using nicotine-containing products for at&#xD;
             least 4 weeks prior to entry to study.&#xD;
&#xD;
         10. Negative urine pregnancy test (only patients with childbearing potential) at screening&#xD;
             and use of adequate contraceptive measures from screening until 6 months after the&#xD;
             study treatment administration:&#xD;
&#xD;
               1. A patient with childbearing potential should be using a reliable contraception&#xD;
                  method: intrauterine device (hormonal or non-hormonal); oral combination pill or&#xD;
                  hormonal contraception patch; or two of the following: intra-vaginal hormonal&#xD;
                  ring, oral contraceptive containing progestin only, spermicidal foam, condom,&#xD;
                  sterilization of male sexual partner (surgical vasectomy).&#xD;
&#xD;
               2. A patient with no current heterosexual relationship may be included according to&#xD;
                  the judgement of the Investigator.&#xD;
&#xD;
               3. If the patient is surgically sterile or whose menopause occurred 2 years&#xD;
                  previously at the minimum, no contraception is required nor pregnancy test.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. A patient who had an N2/N3 or a T4 stage breast cancer or an inflammatory breast&#xD;
             cancer at the time of the original diagnosis.&#xD;
&#xD;
          2. A patient with evidence (clinical, laboratory, or imaging) or history of a neoplasm&#xD;
             other than breast cancer (except basal cell carcinoma or cervical in situ carcinoma).&#xD;
&#xD;
          3. A patient known to be pregnant, lactating or having a positive or indeterminate&#xD;
             pregnancy test.&#xD;
&#xD;
          4. Treatment with COX-2 inhibitors should be interrupted from one week prior until 2&#xD;
             weeks post surgery and treatment with Lymfactin®.&#xD;
&#xD;
          5. Previous treatment with, or participation in, trial of a gene therapy product.&#xD;
&#xD;
          6. Current participation or participation in the preceding two months, in any clinical&#xD;
             study apart from a noninterventional study.&#xD;
&#xD;
          7. Current treatment with immunosuppressive drugs.&#xD;
&#xD;
          8. Current or history of drug, including nicotinecontaining products, or alcohol abuse.&#xD;
&#xD;
          9. Known human immunodeficiency virus- or acquired immunodeficiency syndrome-related&#xD;
             illness.&#xD;
&#xD;
         10. Allergy to any ingredients of the Lymfactin® solution for injection (glycerol,&#xD;
             N-2-hydroxyethylpiperazine-N´-2-ethanesulfonic acid (HEPES), sodium hydroxide).&#xD;
&#xD;
         11. Other severe acute or chronic medical or psychiatric condition or laboratory&#xD;
             abnormality that may increase the risk associated with study participation or study&#xD;
             drug administration, that would affect the patient's ability to follow study-related&#xD;
             procedures, or that may interfere with the interpretation of study results and, in the&#xD;
             Investigator's opinion, would make the patient inappropriate for entry into this&#xD;
             study.&#xD;
&#xD;
         12. Doubtful availability, in the opinion of the Investigator, to complete the study.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anne Saarikko, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>HUCH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Toeoeloe Hospital, Department of Plastic Surgery</name>
      <address>
        <city>Helsinki</city>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tampere University Hospital, Department of Plastic Surgery</name>
      <address>
        <city>Tampere</city>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Turku University Hospital, Department of Plastic Surgery</name>
      <address>
        <city>Turku</city>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Finland</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>November 10, 2016</study_first_submitted>
  <study_first_submitted_qc>December 13, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 16, 2016</study_first_posted>
  <last_update_submitted>April 20, 2023</last_update_submitted>
  <last_update_submitted_qc>April 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 24, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Lymphedema, Breast cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Lymphedema</mesh_term>
  </condition_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/NCT02994771
org study id: CL12001
nct id: NCT02994771
lead sponsor: 
has dmc: Yes
Indicated for the Treatment of Secondary Lymphedema Associated with the Treatment of Breast
      Cancer.

      Primary objective is to evaluate the safety and tolerability of a single dose of Lymfactin®
      in patients with secondary lymphedema associated with the treatment of breast cancer.
This is an open label, multi-center, uncontrolled first in human trial that uses a standard 3
      + 3 dose escalation scheme. Lymfactin® will be administered as a single dose by ex vivo
      perinodal injection into the fat pad of a flap of tissue containing lymph nodes from the
      abdominal wall. This flap of tissue will then be surgically implanted into the axillary
      region of the affected arm. This treatment with Lymfactin® may be performed in conjunction
      with or without breast reconstruction surgery.

      Up to two dose cohorts are planned to be included. Each dose of Lymfactin® will be
      administered as a single dose via perinodal injection in a volume of 2 mL:

        -  Cohort 1: Lymfactin® [1 x 10E10 vp]

        -  Cohort 2: Lymfactin® [1 x 10E11 vp]

      Should the dose escalation go up to Cohort 2 with initiation of a subsequent Extension Cohort
      a total of 15 - 21 patients may be treated in this study.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety as measured by number of patients with treatment related adverse events and serious adverse events as assessed by CTCAE v4.0
time frame: baseline to 1 year, yearly up to 5 years
description: Adverse events and serious adverse events assessed by CTCAE v4.0 to evaluate the safety profile after administration of Lymfactin
measure: CT scan of chest and abdomen
time frame: baseline, yearly up to 5 years
description: Changes in the CT scan of chest and abdomen in order to detect malignancies
measure: Biodistribution of Lymfactin in blood
time frame: 90 days
description: Changes in Lymfactin genome copy number in blood
measure: Formation of anti-Lymfactin antibodies
time frame: 6 months
description: Changes in the anti-Lymfactin antibody titer in blood
measure: Measurement of the volume of the arms
time frame: baseline, 6, 12, 24 and 36 months
description: Changes in the volume of the affected arm and comparison to the unaffected arm
measure: Measurement of the lymphatic flow of the affected arm by quantitative lymphoscintigraphy (99Tc-nanocolloid clearance rate with calculation of transport index)
time frame: baseline, 12, 24 and 36 months
description: Assessment of the changes in the lymphatic flow
measure: Questionnaire according to the Lymphedema Quality of Life Inventory (LQOLI)
time frame: baseline, 6, 12, 24 and 36 months
description: Assessment of changes in the quality of life using Lymphedema Quality of Life Inventory (LQOLI) in which patients assess how their lymphedema is affecting the activities of daily living. LQOLI consists of three dimensions: Physical, psychosocial and practical, which are reported separately as the mean score of each dimension. Each dimension of the LQOLI is scored from 0 to 3, where score 0 means "no impact", 1 means "a little bit impact", 2 means "somewhat impact", and 3 means "significant impact" on the quality of life of the patient, the smaller score thus being the better.
arm group label: Lymfactin® [1 x 10E10 vp]
arm group type: Active Comparator
description: Lymfactin® [1 x 10E10 vp] will be administered as a single dose via perinodal injection in a volume of 2 mL.
arm group label: Lymfactin® [1 x 10E11 vp]
arm group type: Active Comparator
description: Lymfactin® [1 x 10E11 vp] will be administered as a single dose via perinodal injection in a volume of 2 mL.
intervention type: Drug
intervention name: Lymfactin® [1 x 10E10 vp]
description: Lymfactin® [1 x 10E10 vp] will be administered as a single dose via perinodal injection in a volume of 2 mL.
arm group label: Lymfactin® [1 x 10E10 vp]
other name: LX-1101, AdAptVEGF-C Adenoviral Vector
intervention type: Drug
intervention name: Lymfactin® [1 x 10E11 vp]
description: Lymfactin® [1 x 10E11 vp] will be administered as a single dose via perinodal injection in a volume of 2 mL.
arm group label: Lymfactin® [1 x 10E11 vp]
other name: LX-1101, AdAptVEGF-C Adenoviral Vector
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Anne Saarikko, MD, PhD
role: Principal Investigator
affiliation: HUCH
facility: 
facility: 
facility: 
country: Finland
responsible party type: Sponsor
mesh term: Neoplasm Metastasis
mesh term: Lymphedema
sharing ipd: No