xml: <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/NCT06015854</url>
    </required_header>
    <id_info>
      <org_study_id>Vvax001-UMCG-02</org_study_id>
      <nct_id>NCT06015854</nct_id>
    </id_info>
    <brief_title>Vvax001 Cancer Vaccine in Premalignant Cervical Lesions - Phase II</brief_title>
    <acronym>Vvax</acronym>
    <official_title>A Phase II Study to Determine the Efficacy and Safety of Vvax001, a Therapeutic Semliki Forest Virus Based Cancer Vaccine, in Patients With HPV-16 Induced Grade 3 Cervical Intraepithelial Neoplasia</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University Medical Center Groningen</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Dutch Cancer Society</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>ViciniVax B.V</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>University Medical Center Groningen</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is an open label phase II study in patients with newly diagnosed human papilloma virus&#xD;
        type 16 (HPV16) induced cervical intraepithelial neoplasia grade 3 (CIN3). Patients will be&#xD;
        treated with three doses of Vvax001 immunization with an interval of 3 weeks between each&#xD;
        immunization to induce histopathological regression and HPV clearance. Regression of CIN3&#xD;
        lesions will be monitored using colposcopy in week 9, week 17 and week 25. When complete&#xD;
        regression of the CIN3 lesion is observed by colposcopy, a biopsy will be taken in week 25 to&#xD;
        confirm regression histologically. A positive histologic regression is defined as a reduction&#xD;
        from CIN3 to CIN1 or no dysplasia. Patients with a complete regression will not undergo the&#xD;
        standard-of-care loop excision of the transformation zone (LETZ) and will be followed-up&#xD;
        after the study by cytology at 3, 6 and 12 months. If complete regression has not occurred by&#xD;
        25 weeks, a standard-of-care LETZ will be performed.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Human papillomavirus (HPV) infection is the most important cause of premalignant cervical&#xD;
        disease. Current treatment for premalignant HPV-induced genital lesions primarily relies on&#xD;
        surgery, which can be discomforting and carries a risk of complications like bleeding,&#xD;
        cervical stenosis and/or incompetence which may lead to infertility and partus&#xD;
        prematuris/immaturis. Above all, it does not necessarily eradicate the underlying HPV&#xD;
        infection completely.&#xD;
  &#xD;
        Therapeutic immunization is a very attractive alternative to the current treatment options&#xD;
        for precancerous lesions and (invasive) cancer. The immune cells induced by cancer&#xD;
        immunotherapy can target the tumor cells and kill them. When long-lasting immunity is induced&#xD;
        the immunotherapy may prevent recurrence of the disease. Therefore, the approach taken in&#xD;
        this study is to immunize with a replication-incompetent Semliki Forest Virus (SFV) vector&#xD;
        encoding HPV-derived tumor antigens. Intramuscular immunization with these&#xD;
        replication-incompetent SFV particles (Vvax001) is aimed at eliciting a therapeutic&#xD;
        anti-tumor response.&#xD;
  &#xD;
        A phase I study has been conducted in which vaccination with Vvax001 induced&#xD;
        HPV16-E6,7-specific immune responses in women previously treated for cervical intraepithelial&#xD;
        neoplasia (CIN) or cervical cancer (CC). Intramuscular immunization with Vvax001 was well&#xD;
        tolerated, showing only mild to moderate local adverse reactions. Altogether, the data of&#xD;
        this study justify testing of Vvax001 in CIN3 patients in the current phase II study.&#xD;
  &#xD;
        In this open label phase II study patients with newly diagnosed HPV16 induced cervical&#xD;
        intraepithelial neoplasia grade 3 (CIN3) will receive three bilateral intramuscular&#xD;
        immunizations of Vvax001 (5x107 infectious particles [IP]) with an interval of 3 weeks&#xD;
        between vaccinations at week 0, week 3 and week 6.&#xD;
  &#xD;
        Patients will be monitored for regression of CIN3 lesions by colposcopy and digital imaging&#xD;
        at week 9, week 17 and week 25. When complete regression of the CIN3 lesion is observed by&#xD;
        colposcopy, a biopsy will be taken in week 25 to confirm regression and no LETZ will be&#xD;
        performed. If complete regression has not occurred by 25 weeks, the standard-of-care LETZ&#xD;
        will be performed. If progression of the CIN3 lesion is observed during the 25 week interval,&#xD;
        a biopsy will be taken to confirm pathological progression. If pathological progression has&#xD;
        occurred, patients will immediately undergo a LETZ. If no pathological progression has&#xD;
        occurred, patients will continue to be monitored by colposcopy.&#xD;
  &#xD;
        Patients with a complete regression will be followed-up by cytology at 3, 6 and 12 months&#xD;
        after exit from the study. Hereafter, patients will be monitored through regular screening&#xD;
        programs.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">March 23, 2021</start_date>
    <completion_date type="Anticipated">April 1, 2024</completion_date>
    <primary_completion_date type="Anticipated">February 6, 2024</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>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Clinical efficacy of Vvax001</measure>
      <time_frame>At week 25 (19 weeks after the last immunization)</time_frame>
      <description>Clinical efficacy is determined by a pathological regression of the premalignant CIN3 lesion in pre- versus post-treatment tissue samples. A positive histologic regression is defined as a reduction from CIN3 to CIN1, or a reduction from CIN3 to no dysplasia.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Immunogenicity of Vvax001</measure>
      <time_frame>At weeks 7, 9, 17 and 25, respectively 1 week, 3 weeks, 11 weeks and 19 weeks after the last vaccination</time_frame>
      <description>HPV-16 E6,7-specific T-cell immune responses in the peripheral blood will be measured by IFN-y ELISPOT</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>HPV 16 clearance</measure>
      <time_frame>Week 25 (19 weeks after the last immunization)</time_frame>
      <description>Standard HPV testing by molecular analysis will be performed on tissue collected during the last study visit.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Side effects/ adverse events</measure>
      <time_frame>up to 19 weeks after the last immunization</time_frame>
      <description>To monitor the side effects/ adverse events related to intramuscular administration of Vvax001. Toxicity will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">18</enrollment>
    <condition>CIN3</condition>
    <condition>Cervical Intraepithelial Neoplasia</condition>
    <condition>Cervical Intraepithelial Neoplasia Grade 3</condition>
    <condition>HPV 16 Infection</condition>
    <arm_group>
      <arm_group_label>HPV16+ CIN3</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients with histological proven HPV16-positive cervical intraepithelial neoplasia grade 3.</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Vvax001 therapeutic cancer vaccine</intervention_name>
      <description>Patients will receive three immunizations, with an interval of 3 weeks between each immunization at weeks 0, 3 and 6. Each vaccination will be given as two injections; 1 injection in each leg. The injections will be administered intramuscularly in the upper legs, preferably in the m. vastus lateralis.</description>
      <arm_group_label>HPV16+ CIN3</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Newly diagnosed HPV16-positive CIN3.&#xD;
  &#xD;
            -  Age of 18 years and older.&#xD;
  &#xD;
            -  Patients of child-bearing potential should test negative using a serum pregnancy test&#xD;
               and agree to utilize effective contraception during the entire treatment and follow-up&#xD;
               period of the study.&#xD;
  &#xD;
            -  Written informed consent according to local guidelines.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  PAP5 lesions.&#xD;
  &#xD;
            -  Previously undergone treatment for CIN lesions.&#xD;
  &#xD;
            -  Adenocarcinoma in situ within CIN3 lesion.&#xD;
  &#xD;
            -  History of an autoimmune disease or other systemic intercurrent disease that might&#xD;
               affect the immunocompetence of the patient, or current or prior use (4 weeks before&#xD;
               start of the study) of high dose immunosuppressive therapy.&#xD;
  &#xD;
            -  History of a malignancy except curatively treated low-stage tumors with a histology&#xD;
               that can be differentiated from the cervical cancer type.&#xD;
  &#xD;
            -  Participation in a study with another investigational drug within 30 days prior to the&#xD;
               enrolment in this study.&#xD;
  &#xD;
            -  Clinically significant findings as judged by the Investigator on screening/study entry&#xD;
               including those from the Biochemistry, Hematology and urinalysis performed at&#xD;
               baseline.&#xD;
  &#xD;
            -  Any condition that in the opinion of the investigator could interfere with the conduct&#xD;
               of the study.&#xD;
  &#xD;
            -  Pregnancy.&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Yigit</last_name>
      <phone>003153616161</phone>
      <email>r.yigit@umcg.nl</email>
    </overall_contact>
    <location>
      <facility>
        <name>University Medical Center Groningen (UMCG)</name>
        <address>
          <city>Groningen</city>
          <zip>9700 RB</zip>
          <country>Netherlands</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Anneke Eerkens, MSc</last_name>
        <phone>0015 361 6161</phone>
        <email>a.l.eerkens@umcg.nl</email>
      </contact>
      <investigator>
        <last_name>Refika Yigit, MD, PhD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Netherlands</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 23, 2023</study_first_submitted>
    <study_first_submitted_qc>August 23, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 29, 2023</study_first_posted>
    <last_update_submitted>August 23, 2023</last_update_submitted>
    <last_update_submitted_qc>August 23, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 29, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Neoplasms</mesh_term>
      <mesh_term>Carcinoma in Situ</mesh_term>
      <mesh_term>Uterine Cervical Dysplasia</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06015854
  org study id: Vvax001-UMCG-02
  nct id: NCT06015854
  lead sponsor: 
  collaborator: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  This is an open label phase II study in patients with newly diagnosed human papilloma virus
        type 16 (HPV16) induced cervical intraepithelial neoplasia grade 3 (CIN3). Patients will be
        treated with three doses of Vvax001 immunization with an interval of 3 weeks between each
        immunization to induce histopathological regression and HPV clearance. Regression of CIN3
        lesions will be monitored using colposcopy in week 9, week 17 and week 25. When complete
        regression of the CIN3 lesion is observed by colposcopy, a biopsy will be taken in week 25 to
        confirm regression histologically. A positive histologic regression is defined as a reduction
        from CIN3 to CIN1 or no dysplasia. Patients with a complete regression will not undergo the
        standard-of-care loop excision of the transformation zone (LETZ) and will be followed-up
        after the study by cytology at 3, 6 and 12 months. If complete regression has not occurred by
        25 weeks, a standard-of-care LETZ will be performed.
  Human papillomavirus (HPV) infection is the most important cause of premalignant cervical
        disease. Current treatment for premalignant HPV-induced genital lesions primarily relies on
        surgery, which can be discomforting and carries a risk of complications like bleeding,
        cervical stenosis and/or incompetence which may lead to infertility and partus
        prematuris/immaturis. Above all, it does not necessarily eradicate the underlying HPV
        infection completely.
  
        Therapeutic immunization is a very attractive alternative to the current treatment options
        for precancerous lesions and (invasive) cancer. The immune cells induced by cancer
        immunotherapy can target the tumor cells and kill them. When long-lasting immunity is induced
        the immunotherapy may prevent recurrence of the disease. Therefore, the approach taken in
        this study is to immunize with a replication-incompetent Semliki Forest Virus (SFV) vector
        encoding HPV-derived tumor antigens. Intramuscular immunization with these
        replication-incompetent SFV particles (Vvax001) is aimed at eliciting a therapeutic
        anti-tumor response.
  
        A phase I study has been conducted in which vaccination with Vvax001 induced
        HPV16-E6,7-specific immune responses in women previously treated for cervical intraepithelial
        neoplasia (CIN) or cervical cancer (CC). Intramuscular immunization with Vvax001 was well
        tolerated, showing only mild to moderate local adverse reactions. Altogether, the data of
        this study justify testing of Vvax001 in CIN3 patients in the current phase II study.
  
        In this open label phase II study patients with newly diagnosed HPV16 induced cervical
        intraepithelial neoplasia grade 3 (CIN3) will receive three bilateral intramuscular
        immunizations of Vvax001 (5x107 infectious particles [IP]) with an interval of 3 weeks
        between vaccinations at week 0, week 3 and week 6.
  
        Patients will be monitored for regression of CIN3 lesions by colposcopy and digital imaging
        at week 9, week 17 and week 25. When complete regression of the CIN3 lesion is observed by
        colposcopy, a biopsy will be taken in week 25 to confirm regression and no LETZ will be
        performed. If complete regression has not occurred by 25 weeks, the standard-of-care LETZ
        will be performed. If progression of the CIN3 lesion is observed during the 25 week interval,
        a biopsy will be taken to confirm pathological progression. If pathological progression has
        occurred, patients will immediately undergo a LETZ. If no pathological progression has
        occurred, patients will continue to be monitored by colposcopy.
  
        Patients with a complete regression will be followed-up by cytology at 3, 6 and 12 months
        after exit from the study. Hereafter, patients will be monitored through regular screening
        programs.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Clinical efficacy of Vvax001
  time frame: At week 25 (19 weeks after the last immunization)
  description: Clinical efficacy is determined by a pathological regression of the premalignant CIN3 lesion in pre- versus post-treatment tissue samples. A positive histologic regression is defined as a reduction from CIN3 to CIN1, or a reduction from CIN3 to no dysplasia.
  measure: Immunogenicity of Vvax001
  time frame: At weeks 7, 9, 17 and 25, respectively 1 week, 3 weeks, 11 weeks and 19 weeks after the last vaccination
  description: HPV-16 E6,7-specific T-cell immune responses in the peripheral blood will be measured by IFN-y ELISPOT
  measure: HPV 16 clearance
  time frame: Week 25 (19 weeks after the last immunization)
  description: Standard HPV testing by molecular analysis will be performed on tissue collected during the last study visit.
  measure: Side effects/ adverse events
  time frame: up to 19 weeks after the last immunization
  description: To monitor the side effects/ adverse events related to intramuscular administration of Vvax001. Toxicity will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
  arm group label: HPV16+ CIN3
  arm group type: Experimental
  description: Patients with histological proven HPV16-positive cervical intraepithelial neoplasia grade 3.
  intervention type: Biological
  intervention name: Vvax001 therapeutic cancer vaccine
  description: Patients will receive three immunizations, with an interval of 3 weeks between each immunization at weeks 0, 3 and 6. Each vaccination will be given as two injections; 1 injection in each leg. The injections will be administered intramuscularly in the upper legs, preferably in the m. vastus lateralis.
  arm group label: HPV16+ CIN3
  criteria: 
  gender: Female
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Yigit
  phone: 003153616161
  email: r.yigit@umcg.nl
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  country: Netherlands
  responsible party type: Sponsor
  mesh term: Neoplasms
  mesh term: Carcinoma in Situ
  mesh term: Uterine Cervical Dysplasia
  sharing ipd: Undecided