<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/NCT02261714</url>
  </required_header>
  <id_info>
    <org_study_id>CT TG01-01</org_study_id>
    <nct_id>NCT02261714</nct_id>
  </id_info>
  <brief_title>Antigen-specific Cancer Immunotherapy (TG01) and Gemcitabine as Adjuvant Therapy in Resected Pancreatic Cancer</brief_title>
  <official_title>A Phase I/II Trial of TG01 and Gemcitabine as Adjuvant Therapy for Treating Patients With Resected Adenocarcinoma of the Pancreas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Targovax ASA</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Targovax ASA</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to investigate the effect of TG01 and Granulocyte macrophage&#xD;
      colony stimulating factor (GM-CSF) when given in addition to gemcitabine (chemotherapy) and&#xD;
&#xD;
        -  Understand any possible side effects of the additional use of TG01/GM-CSF with&#xD;
           gemcitabine&#xD;
&#xD;
        -  Investigate whether TG01/GM-CSF when given with gemcitabine can produce an immune&#xD;
           response&#xD;
&#xD;
        -  Investigate if the treatment can delay or reduce recurrence of the disease&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">May 2019</completion_date>
  <primary_completion_date type="Actual">May 2019</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>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>Patients' Safety During Study</measure>
    <time_frame>2 years</time_frame>
    <description>Assess the safety (number and nature of Adverse events and laboratory data occurring during study (before, during and after chemotherapy is given) in subjects treated with the Pancreatic Cancer ASCI</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Patients' Immune Response</measure>
    <time_frame>During the 2 years of treatment</time_frame>
    <description>Assess the Immune response (DTH responses and Proliferative T-cell responses) up to 2 years of treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical Efficacy</measure>
    <time_frame>DFS was followed for up to 2 years and OS until last patient included had been in the study for 3 years.</time_frame>
    <description>Efficacy exploring disease free survival and overall survival.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Relationship Between (KRAS) Status and Clinical Efficacy</measure>
    <time_frame>2 years</time_frame>
    <description>Relationship between KRAS status and recurrence</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Pancreatic Cancer, Resected</condition>
  <arm_group>
    <arm_group_label>TG01/GM-CSF and Gemcitabine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>TG01</intervention_name>
    <description>TG01 and GM-CSF will be administered on days 1, 8, 15, 22 and 36. TG01 alone will also be given on days 36 and 50 for DTH assessment. Gemcitabine will start at least 3 weeks after TG01/GM-CSF and will be given on days 1, 8 and 15 of a four-weeks cycle up to 6 cycles in total.&#xD;
Once chemotherapy is completed, GM-CSF and TG01 injections will resume and will be given every 4 weeks from the end of the chemotherapy period up to week 52 (plus once at week 5 post-chemotherapy) and then every 12 weeks from week 52 to week 104. TG01 alone will be given 8 weeks after the end of chemotherapy for DTH assessment.&#xD;
TG01 will be given at a dose of 0.70 mg/injection and GM-CSF will be given at a dose of 30 micrograms both as intradermal injections.&#xD;
Gemcitabine will be given at a dose of 1000 mg/m2 iv over 30 minutes</description>
    <arm_group_label>TG01/GM-CSF and Gemcitabine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>TG01</intervention_name>
    <description>For patients not able to start TG01 quickly after surgery, the vaccination can start at the same time as the chemotherapy as long as they start within 12 weeks from surgery. Gemcitabine will start at the same time as TG01/GM-CSF and will be given on days 1, 8 and 15 of a four-weeks cycle up to 6 cycles in total.&#xD;
TG01 will be given at a dose of 0.70 mg/injection and GM-CSF will be given at a dose of 30 micrograms both as intradermal injections.&#xD;
Gemcitabine will be given at a dose of 1000 mg/m2 iv over 30 minutes</description>
    <arm_group_label>TG01/GM-CSF and Gemcitabine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically or cytologically confirmed diagnosis of adenocarcinoma of the pancreas&#xD;
&#xD;
          2. Stage I or II disease (clinical stage T1-3, N0-1, M0 by AJCC staging criteria).&#xD;
&#xD;
          3. Successful surgical resection&#xD;
&#xD;
               -  Complete resection (R0) or with microscopic residual disease (R1)&#xD;
&#xD;
               -  Expected to receive gemcitabine monotherapy as adjuvant chemotherapy&#xD;
&#xD;
          4. Laboratory Values:&#xD;
&#xD;
               -  Absolute neutrophil count ≥ 1.5 x 10^9/l&#xD;
&#xD;
               -  Platelets ≥100 x 10^9/l&#xD;
&#xD;
               -  Haemoglobin ≥ 9 g/dl&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5 x UNL&#xD;
&#xD;
               -  Serum creatinine ≤ 1.5 x UNL&#xD;
&#xD;
               -  Albumin ≥ 2.5 g/dl&#xD;
&#xD;
               -  AST or ALT ≥ 5 x UNL&#xD;
&#xD;
          5. 18 years of age or older.&#xD;
&#xD;
          6. ECOG performance status (PS) of 0-1.&#xD;
&#xD;
          7. Life expectancy of at least 6 months&#xD;
&#xD;
          8. Men and women of childbearing potential must be willing to use effective methods of&#xD;
             contraception to prevent pregnancy&#xD;
&#xD;
          9. Provide written (signed) informed consent to participate in the trial prior to any&#xD;
             trial specific screening procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Has received an investigational drug within 4 weeks prior to Trial drug administration&#xD;
&#xD;
          2. Has received previous therapy for pancreatic cancer including radiation or&#xD;
             chemotherapy (except for the primary resection or primary neoadjuvant chemotherapy).&#xD;
&#xD;
          3. Is currently receiving any agent with a known effect on the immune system, unless at&#xD;
             dose levels that are not immunosuppressive (e.g. Prednisone at 10 mg/day or less or as&#xD;
             inhaled steroid at doses used for the treatment of asthma).&#xD;
&#xD;
          4. Has any other serious illnesses or medical conditions such as, but not limited to:&#xD;
&#xD;
               -  Any uncontrolled infection&#xD;
&#xD;
               -  Uncontrolled cardiac failure classification III or IV (NY Heart Association)&#xD;
&#xD;
               -  Uncontrolled systemic and gastro-intestinal inflammatory conditions&#xD;
&#xD;
               -  Bone marrow dysplasia&#xD;
&#xD;
               -  History of auto-immune disease&#xD;
&#xD;
               -  History of adverse reactions to vaccines&#xD;
&#xD;
          5. Known history of positive tests for HIV/AIDS, hepatitis B or C&#xD;
&#xD;
          6. Pregnant or lactating females or have no pregnancy test at baseline (postmenopausal&#xD;
             women must have been amenorrhoeic for at least 12 months to be considered of&#xD;
             non-childbearing potential).&#xD;
&#xD;
          7. Contraindication to gemcitabine treatment&#xD;
&#xD;
          8. Have had any other malignancies within last 3 years (except for adequately treated&#xD;
             carcinoma of the cervix or basal or squamous cell skin cancer)&#xD;
&#xD;
          9. Known malignant brain lesion(s)&#xD;
&#xD;
         10. Are unlikely to start chemotherapy within 12 weeks of surgery (e.g. delayed wound&#xD;
             healing, or infection, etc.)&#xD;
&#xD;
         11. Are not expected to complete 6 cycles of chemotherapy&#xD;
&#xD;
         12. Are planned to receive yellow fever or other live (attenuated) vaccines during the&#xD;
             course of study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Daniel PALMER</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Liverpool Molecular and Clinical Cancer Medicine /UCD Duncan Building / Daulby Street / Liverpool</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Juan VALLE</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Manchester / The Christie NHS Foundation Trust /Wilmslow Road / Manchester</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Svein DUELAND</last_name>
    <role>Principal Investigator</role>
    <affiliation>Oslo University Hospital HF / the Norwegian Radium Hospital / Ullernchausseen 70 / Oslo</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Yuk Ting MA</last_name>
    <role>Principal Investigator</role>
    <affiliation>Queen Elizabeth University Hospital / Edgaston / Birmingham</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Emiliano Calvo</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centro Integral Oncologico Clara Campal / Hospital HM Universitario Sanchinarro / Madrid</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Oslo University Hospital HF the Norwegian Radium Hospital</name>
      <address>
        <city>Oslo</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Integral Oncologico Clara Campal / Hospital HM Universitario Sanchinarro</name>
      <address>
        <city>Madrid</city>
        <zip>28050</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth University Hospital / Edgaston /</name>
      <address>
        <city>Birmingham</city>
        <zip>B15 2TH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Liverpool / Molecular and Clinical Cancer Medicine</name>
      <address>
        <city>Liverpool</city>
        <zip>L69 3GA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Manchester / The Christie NHS Foundation Trust</name>
      <address>
        <city>Manchester</city>
        <zip>M20 43 X</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Norway</country>
    <country>Spain</country>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Gjertsen MK, Buanes T, Rosseland AR, Bakka A, Gladhaug I, Soreide O, Eriksen JA, Moller M, Baksaas I, Lothe RA, Saeterdal I, Gaudernack G. Intradermal ras peptide vaccination with granulocyte-macrophage colony-stimulating factor as adjuvant: Clinical and immunological responses in patients with pancreatic adenocarcinoma. Int J Cancer. 2001 May 1;92(3):441-50. doi: 10.1002/ijc.1205.</citation>
    <PMID>11291084</PMID>
  </reference>
  <reference>
    <citation>Weden S, Klemp M, Gladhaug IP, Moller M, Eriksen JA, Gaudernack G, Buanes T. Long-term follow-up of patients with resected pancreatic cancer following vaccination against mutant K-ras. Int J Cancer. 2011 Mar 1;128(5):1120-8. doi: 10.1002/ijc.25449.</citation>
    <PMID>20473937</PMID>
  </reference>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>March 24, 2014</study_first_submitted>
  <study_first_submitted_qc>October 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2014</study_first_posted>
  <results_first_submitted>April 8, 2020</results_first_submitted>
  <results_first_submitted_qc>May 13, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">May 14, 2020</results_first_posted>
  <last_update_submitted>May 13, 2020</last_update_submitted>
  <last_update_submitted_qc>May 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pancreatic cancer, resected</keyword>
  <keyword>Vaccine</keyword>
  <keyword>KRAS</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pancreatic Neoplasms</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 27, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/14/NCT02261714/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 2, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/14/NCT02261714/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>TG01/GM-CSF and Gemcitabine</title>
          <description>TG01: TG01 and GM-CSF will be administered on days 1, 8, 15, 22 and 36. TG01 alone will also be given on days 36 and 50 for DTH assessment. Gemcitabine will start at least 3 weeks after TG01/GM-CSF and will be given on days 1, 8 and 15 of a four-weeks cycle up to 6 cycles in total. Once chemotherapy is completed, GM-CSF and TG01 injections will resume and will be given every 4 weeks from the end of the chemotherapy period up to week 52 (plus once at week 5 post-chemotherapy) and then every 12 weeks from week 52 to week 104. TG01 alone will be given 8 weeks after the end of chemotherapy for DTH assessment.&#xD;
TG01 will be given at a dose of 0.70 mg/injection and GM-CSF will be given at a dose of 30 micrograms both as intradermal injections.&#xD;
Gemcitabine will be given at a dose of 1000 mg/m2 iv over 30 minutes TG01: For patients not able to start TG01 quickly after surgery, the vaccination can start at the same time as the chemotherapy as long as they start within 12 weeks from surge</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="28"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>TG01/GM-CSF and Gemcitabine</title>
          <description>TG01: TG01 and GM-CSF will be administered on days 1, 8, 15, 22 and 36. TG01 alone will also be given on days 36 and 50 for DTH assessment. Gemcitabine will start at least 3 weeks after TG01/GM-CSF and will be given on days 1, 8 and 15 of a four-weeks cycle up to 6 cycles in total. Once chemotherapy is completed, GM-CSF and TG01 injections will resume and will be given every 4 weeks from the end of the chemotherapy period up to week 52 (plus once at week 5 post-chemotherapy) and then every 12 weeks from week 52 to week 104. TG01 alone will be given 8 weeks after the end of chemotherapy for DTH assessment. TG01 will be given at a dose of 0.70 mg/injection and GM-CSF will be given at a dose of 30 micrograms both as intradermal injections. Gemcitabine will be given at a dose of 1000 mg/m2 iv over 30 minutes TG01: For patients not able to start TG01 quickly after surgery, the vaccination can start at the same time as the chemotherapy as long as they start within 12 weeks from surge</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="32"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="64.1" lower_limit="46" upper_limit="79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Norway</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United Kingdom</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Patients' Safety During Study</title>
        <description>Assess the safety (number and nature of Adverse events and laboratory data occurring during study (before, during and after chemotherapy is given) in subjects treated with the Pancreatic Cancer ASCI</description>
        <time_frame>2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>TG01/GM-CSF and Gemcitabine</title>
            <description>TG01: TG01 and GM-CSF will be administered on days 1, 8, 15, 22 and 36. TG01 alone will also be given on days 36 and 50 for DTH assessment. Gemcitabine will start at least 3 weeks after TG01/GM-CSF and will be given on days 1, 8 and 15 of a four-weeks cycle up to 6 cycles in total. Once chemotherapy is completed, GM-CSF and TG01 injections will resume and will be given every 4 weeks from the end of the chemotherapy period up to week 52 (plus once at week 5 post-chemotherapy) and then every 12 weeks from week 52 to week 104. TG01 alone will be given 8 weeks after the end of chemotherapy for DTH assessment.&#xD;
TG01 will be given at a dose of 0.70 mg/injection and GM-CSF will be given at a dose of 30 micrograms both as intradermal injections.&#xD;
Gemcitabine will be given at a dose of 1000 mg/m2 iv over 30 minutes TG01: For patients not able to start TG01 quickly after surgery, the vaccination can start at the same time as the chemotherapy as long as they start within 12 weeks from surge</description>
          </group>
        </group_list>
        <measure>
          <title>Patients' Safety During Study</title>
          <description>Assess the safety (number and nature of Adverse events and laboratory data occurring during study (before, during and after chemotherapy is given) in subjects treated with the Pancreatic Cancer ASCI</description>
          <units>Events related to TG01 and /or GM-CSF</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AEs related to TG01 and/or GM-CSF</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs related to TG01 and/or GM-CSF</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Patients' Immune Response</title>
        <description>Assess the Immune response (DTH responses and Proliferative T-cell responses) up to 2 years of treatment</description>
        <time_frame>During the 2 years of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>TG01/GM-CSF and Gemcitabine</title>
            <description>TG01: TG01 and GM-CSF will be administered on days 1, 8, 15, 22 and 36. TG01 alone will also be given on days 36 and 50 for DTH assessment. Gemcitabine will start at least 3 weeks after TG01/GM-CSF and will be given on days 1, 8 and 15 of a four-weeks cycle up to 6 cycles in total. Once chemotherapy is completed, GM-CSF and TG01 injections will resume and will be given every 4 weeks from the end of the chemotherapy period up to week 52 (plus once at week 5 post-chemotherapy) and then every 12 weeks from week 52 to week 104. TG01 alone will be given 8 weeks after the end of chemotherapy for DTH assessment. TG01 will be given at a dose of 0.70 mg/injection and GM-CSF will be given at a dose of 30 micrograms both as intradermal injections. Gemcitabine will be given at a dose of 1000 mg/m2 iv over 30 minutes TG01: For patients not able to start TG01 quickly after surgery, the vaccination can start at the same time as the chemotherapy as long as they start within 12 weeks from surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Patients' Immune Response</title>
          <description>Assess the Immune response (DTH responses and Proliferative T-cell responses) up to 2 years of treatment</description>
          <units>percentage of patients</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Efficacy</title>
        <description>Efficacy exploring disease free survival and overall survival.</description>
        <time_frame>DFS was followed for up to 2 years and OS until last patient included had been in the study for 3 years.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>TG01/GM-CSF and Gemcitabine</title>
            <description>TG01: TG01 and GM-CSF will be administered on days 1, 8, 15, 22 and 36. TG01 alone will also be given on days 36 and 50 for DTH assessment. Gemcitabine will start at least 3 weeks after TG01/GM-CSF and will be given on days 1, 8 and 15 of a four-weeks cycle up to 6 cycles in total. Once chemotherapy is completed, GM-CSF and TG01 injections will resume and will be given every 4 weeks from the end of the chemotherapy period up to week 52 (plus once at week 5 post-chemotherapy) and then every 12 weeks from week 52 to week 104. TG01 alone will be given 8 weeks after the end of chemotherapy for DTH assessment.&#xD;
TG01 will be given at a dose of 0.70 mg/injection and GM-CSF will be given at a dose of 30 micrograms both as intradermal injections.&#xD;
Gemcitabine will be given at a dose of 1000 mg/m2 iv over 30 minutes TG01: For patients not able to start TG01 quickly after surgery, the vaccination can start at the same time as the chemotherapy as long as they start within 12 weeks from surge</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Efficacy</title>
          <description>Efficacy exploring disease free survival and overall survival.</description>
          <units>Months</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Overall survival</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.3" lower_limit="24.0" upper_limit="40.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Disease free survival</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.1" lower_limit="11.1" upper_limit="19.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Relationship Between (KRAS) Status and Clinical Efficacy</title>
        <description>Relationship between KRAS status and recurrence</description>
        <time_frame>2 years</time_frame>
        <population>As the majority of the patients (26 of 32) patients had a KRAS mutation detected, it was not possible to accurately assess relationship between KRAS status and survival outcomes.</population>
        <group_list>
          <group group_id="O1">
            <title>TG01/GM-CSF and Gemcitabine</title>
            <description>TG01: TG01 and GM-CSF will be administered on days 1, 8, 15, 22 and 36. TG01 alone will also be given on days 36 and 50 for DTH assessment. Gemcitabine will start at least 3 weeks after TG01/GM-CSF and will be given on days 1, 8 and 15 of a four-weeks cycle up to 6 cycles in total. Once chemotherapy is completed, GM-CSF and TG01 injections will resume and will be given every 4 weeks from the end of the chemotherapy period up to week 52 (plus once at week 5 post-chemotherapy) and then every 12 weeks from week 52 to week 104. TG01 alone will be given 8 weeks after the end of chemotherapy for DTH assessment. TG01 will be given at a dose of 0.70 mg/injection and GM-CSF will be given at a dose of 30 micrograms both as intradermal injections. Gemcitabine will be given at a dose of 1000 mg/m2 iv over 30 minutes TG01: For patients not able to start TG01 quickly after surgery, the vaccination can start at the same time as the chemotherapy as long as they start within 12 weeks from surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Relationship Between (KRAS) Status and Clinical Efficacy</title>
          <description>Relationship between KRAS status and recurrence</description>
          <population>As the majority of the patients (26 of 32) patients had a KRAS mutation detected, it was not possible to accurately assess relationship between KRAS status and survival outcomes.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>2 years</time_frame>
      <group_list>
        <group group_id="E1">
          <title>TG01/GM-CSF and Gemcitabine</title>
          <description>TG01: TG01 and GM-CSF will be administered on days 1, 8, 15, 22 and 36. TG01 alone will also be given on days 36 and 50 for DTH assessment. Gemcitabine will start at least 3 weeks after TG01/GM-CSF and will be given on days 1, 8 and 15 of a four-weeks cycle up to 6 cycles in total. Once chemotherapy is completed, GM-CSF and TG01 injections will resume and will be given every 4 weeks from the end of the chemotherapy period up to week 52 (plus once at week 5 post-chemotherapy) and then every 12 weeks from week 52 to week 104. TG01 alone will be given 8 weeks after the end of chemotherapy for DTH assessment. TG01 will be given at a dose of 0.70 mg/injection and GM-CSF will be given at a dose of 30 micrograms both as intradermal injections. Gemcitabine will be given at a dose of 1000 mg/m2 iv over 30 minutes TG01: For patients not able to start TG01 quickly after surgery, the vaccination can start at the same time as the chemotherapy as long as they start within 12 weeks from surgery.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaphylactic reaction</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="43" subjects_affected="16" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Chief Medical Officer</name_or_title>
      <organization>Targovax ASA</organization>
      <phone>004721398810</phone>
      <email>contact@targovax.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02261714
org study id: CT TG01-01
nct id: NCT02261714
lead sponsor: 
has dmc: No
The purpose of this study is to investigate the effect of TG01 and Granulocyte macrophage
      colony stimulating factor (GM-CSF) when given in addition to gemcitabine (chemotherapy) and

        -  Understand any possible side effects of the additional use of TG01/GM-CSF with
           gemcitabine

        -  Investigate whether TG01/GM-CSF when given with gemcitabine can produce an immune
           response

        -  Investigate if the treatment can delay or reduce recurrence of the disease
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Patients' Safety During Study
time frame: 2 years
description: Assess the safety (number and nature of Adverse events and laboratory data occurring during study (before, during and after chemotherapy is given) in subjects treated with the Pancreatic Cancer ASCI
measure: Patients' Immune Response
time frame: During the 2 years of treatment
description: Assess the Immune response (DTH responses and Proliferative T-cell responses) up to 2 years of treatment
measure: Clinical Efficacy
time frame: DFS was followed for up to 2 years and OS until last patient included had been in the study for 3 years.
description: Efficacy exploring disease free survival and overall survival.
measure: Relationship Between (KRAS) Status and Clinical Efficacy
time frame: 2 years
description: Relationship between KRAS status and recurrence
arm group label: TG01/GM-CSF and Gemcitabine
arm group type: Experimental
intervention type: Biological
intervention name: TG01
description: TG01 and GM-CSF will be administered on days 1, 8, 15, 22 and 36. TG01 alone will also be given on days 36 and 50 for DTH assessment. Gemcitabine will start at least 3 weeks after TG01/GM-CSF and will be given on days 1, 8 and 15 of a four-weeks cycle up to 6 cycles in total.
Once chemotherapy is completed, GM-CSF and TG01 injections will resume and will be given every 4 weeks from the end of the chemotherapy period up to week 52 (plus once at week 5 post-chemotherapy) and then every 12 weeks from week 52 to week 104. TG01 alone will be given 8 weeks after the end of chemotherapy for DTH assessment.
TG01 will be given at a dose of 0.70 mg/injection and GM-CSF will be given at a dose of 30 micrograms both as intradermal injections.
Gemcitabine will be given at a dose of 1000 mg/m2 iv over 30 minutes
arm group label: TG01/GM-CSF and Gemcitabine
intervention type: Biological
intervention name: TG01
description: For patients not able to start TG01 quickly after surgery, the vaccination can start at the same time as the chemotherapy as long as they start within 12 weeks from surgery. Gemcitabine will start at the same time as TG01/GM-CSF and will be given on days 1, 8 and 15 of a four-weeks cycle up to 6 cycles in total.
TG01 will be given at a dose of 0.70 mg/injection and GM-CSF will be given at a dose of 30 micrograms both as intradermal injections.
Gemcitabine will be given at a dose of 1000 mg/m2 iv over 30 minutes
arm group label: TG01/GM-CSF and Gemcitabine
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Daniel PALMER
role: Principal Investigator
affiliation: University of Liverpool Molecular and Clinical Cancer Medicine /UCD Duncan Building / Daulby Street / Liverpool
last name: Juan VALLE
role: Principal Investigator
affiliation: University of Manchester / The Christie NHS Foundation Trust /Wilmslow Road / Manchester
last name: Svein DUELAND
role: Principal Investigator
affiliation: Oslo University Hospital HF / the Norwegian Radium Hospital / Ullernchausseen 70 / Oslo
last name: Yuk Ting MA
role: Principal Investigator
affiliation: Queen Elizabeth University Hospital / Edgaston / Birmingham
last name: Emiliano Calvo
role: Principal Investigator
affiliation: Centro Integral Oncologico Clara Campal / Hospital HM Universitario Sanchinarro / Madrid
facility: 
facility: 
facility: 
facility: 
facility: 
country: Norway
country: Spain
country: United Kingdom
citation: Gjertsen MK, Buanes T, Rosseland AR, Bakka A, Gladhaug I, Soreide O, Eriksen JA, Moller M, Baksaas I, Lothe RA, Saeterdal I, Gaudernack G. Intradermal ras peptide vaccination with granulocyte-macrophage colony-stimulating factor as adjuvant: Clinical and immunological responses in patients with pancreatic adenocarcinoma. Int J Cancer. 2001 May 1;92(3):441-50. doi: 10.1002/ijc.1205.
PMID: 11291084
citation: Weden S, Klemp M, Gladhaug IP, Moller M, Eriksen JA, Gaudernack G, Buanes T. Long-term follow-up of patients with resected pancreatic cancer following vaccination against mutant K-ras. Int J Cancer. 2011 Mar 1;128(5):1120-8. doi: 10.1002/ijc.25449.
PMID: 20473937
responsible party type: Sponsor
mesh term: Pancreatic Neoplasms
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 