<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/NCT04476251</url>
  </required_header>
  <id_info>
    <org_study_id>200116</org_study_id>
    <secondary_id>20-C-0116</secondary_id>
    <nct_id>NCT04476251</nct_id>
  </id_info>
  <brief_title>E7 TCR T Cell Induction Immunotherapy for Stage IIB-IVA Cervical Cancer</brief_title>
  <official_title>A Pilot Study of E7 TCR T Cell Induction Immunotherapy for Stage IIB-IVA Cervical Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      More than 12,000 cases of cervical cancer are diagnosed in the United States each year. A new&#xD;
      therapy has been developed that involves taking white blood cells from a person, genetically&#xD;
      modifying the cells in a lab so they recognize cancer, and then giving the cells back to the&#xD;
      person. Researchers want to see if this therapy can help people with cervical cancer.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To find out if people with Stage IIB-IVA cervical cancer can safely be given E7 T-cell&#xD;
      receptor (TCR) T cells before they get standard treatment.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      People age 18 and older who have Stage IIB-IVA cervical cancer&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Participants will be screened under a separate protocol. Tests will include:&#xD;
&#xD;
        -  Physical exam&#xD;
&#xD;
        -  Medicine review&#xD;
&#xD;
        -  Blood tests&#xD;
&#xD;
        -  Pregnancy test (if needed)&#xD;
&#xD;
        -  Vein assessment&#xD;
&#xD;
        -  Tumor sample or biopsy&#xD;
&#xD;
        -  Electrocardiogram (to record the hearts electrical activity)&#xD;
&#xD;
        -  Imaging scans, x-rays, and/or endoscopy&#xD;
&#xD;
        -  Heart and/or lung tests.&#xD;
&#xD;
      Some screening tests will be repeated during the study.&#xD;
&#xD;
      Participants will undergo leukapheresis. For this, blood is removed through a needle in the&#xD;
      arm. A machine removes the white blood cells. The rest of the blood is returned through a&#xD;
      needle in the other arm. Participants may need to have a large catheter inserted into a vein.&#xD;
&#xD;
      Participants will stay at the hospital for 2-3 weeks. They will get chemotherapy drugs. They&#xD;
      will get the E7 TCR T cells as an intravenous infusion. They will get the drug aldesleukin.&#xD;
&#xD;
      Participants will visit the National Institutes of Health (NIH) 3 and 6 weeks after&#xD;
      treatment. They will be contacted yearly for 5 years. They will be asked to participate in&#xD;
      long-term follow-up for 15 years....&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
        -  Cervical cancer is the third most common cause of death among women with gynecologic&#xD;
           cancers in the United States. Worldwide, cervical cancer accounts for nearly 300,000&#xD;
           deaths annually.&#xD;
&#xD;
        -  Virtually all cases of cervical cancer result from chronic infection with high-risk&#xD;
           human papillomavirus (HPV), the most common type being HPV16.&#xD;
&#xD;
        -  The treatment of locally advanced cervical cancer consists of chemoradiation +/-&#xD;
           extended field radiation therapy. Participants with International Federation of&#xD;
           Gynecology and Obstetrics (FIGO) (revised 2018) stage III-IVA have the worse prognosis&#xD;
           with approximately 50% of the participants dying from their disease within 5 years.&#xD;
&#xD;
        -  Induction chemotherapy is an active area of study in this type of cancer. The aim of&#xD;
           induction therapy is to reduce the risk of disease recurrence and improve overall&#xD;
           survival.&#xD;
&#xD;
        -  E7 T-cell receptor (TCR) T cells, administered as a single infusion, have demonstrated&#xD;
           safety and clinical activity in advanced, treatment-refractory metastatic HPV+ cancers.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      -To determine the feasibility of induction E7 TCR T cell therapy for FIGO (2018) stage&#xD;
      IIB-IVA, HPV16+ cervical cancer&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
        -  Participants greater than or equal to 18 years old with FIGO (2018) stage IIB-IVA&#xD;
           cervical cancer.&#xD;
&#xD;
        -  The cancer must be human papillomavirus 16 (HPV16+) and participant must be&#xD;
           HLA-A*02:01+.&#xD;
&#xD;
        -  Participants must be treatment-naive (i.e., no prior local or systemic treatment,&#xD;
           including radiation; prior loop electrosurgical excision procedure (LEEP) procedure or&#xD;
           cone biopsy is allowed).&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  This is a single arm, pilot study, testing the feasibility of induction E7 TCR T cell&#xD;
           therapy.&#xD;
&#xD;
        -  Participants will receive a conditioning regimen of cyclophosphamide and fludarabine, a&#xD;
           single infusion of E7 TCR T cells, and systemic aldesleukin.&#xD;
&#xD;
        -  Participants will be referred for standard of care definitive therapy (i.e.,&#xD;
           chemoradiation +/- extended field radiation therapy) within 6 weeks after infusion of E7&#xD;
           TCR T cells.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Multiple logistical challenges&#xD;
  </why_stopped>
  <start_date type="Actual">January 14, 2021</start_date>
  <completion_date type="Actual">September 15, 2021</completion_date>
  <primary_completion_date type="Actual">September 15, 2021</primary_completion_date>
  <phase>Early Phase 1</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>The Fraction of Participants for Whom E7 T-Cell Receptor (TCR) Induction Therapy is Feasible in Participants With Cervical Cancer</measure>
    <time_frame>6 months</time_frame>
    <description>The Fraction of participants for whom E7 T-Cell Receptor (TCR) induction therapy is feasible in participants with cervical cancer</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Fraction of Participants With Relapse-free Survival at 2 Years and 5 Years Following Definitive Standard of Care Therapy</measure>
    <time_frame>2 yrs and 5 yrs</time_frame>
    <description>Fraction of participants with relapse-free survival at 2 years and 5 years estimated from a Kaplan-Meier curve of relapsed free survival following definitive standard of care therapy who achieve a success. Relapsed free survival is defined as the time from date on study to date of relapse of disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fraction of Participants With Grade 1-5 Adverse Events</measure>
    <time_frame>1 year</time_frame>
    <description>To evaluate the safety of E7 induction therapy, the types and grades of toxicity obtained will be reported. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse event.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of E7 T-Cell Receptor (TCR)T Cells Following Completion of Chemoradiation</measure>
    <time_frame>1 year</time_frame>
    <description>Percentage of E7 T-Cell Receptor (TCR)T cells following completion of chemoradiation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fraction of Participants Who Achieve an Objective Response (Partial Response + Complete Response) Following E7 T-Cell Receptor (TCR) T Cell Induction Therapy</measure>
    <time_frame>1 year</time_frame>
    <description>Fraction of participants who achieve an objective response (Partial Response + Complete Response) following E7 induction therapy will be reported. Response may be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response is disappearance of all target lesions. Partial Response is at least a 30% decrease in the sum of the diameters of target lesion; and/or Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST). Complete Metabolic Response is complete resolution of F-fluorodeoxyglucose (FDG) uptake in all lesions, and Partial Metabolic Response is ≥ 30% reduction of the SUL (lean body mass corrected standard uptake value) peak and an absolute drop of 0.8 SULpeak units.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)</measure>
    <time_frame>Date treatment consent signed to date off study, approximately 20 days.</time_frame>
    <description>Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Uterine Cervical Neoplasms</condition>
  <arm_group>
    <arm_group_label>Arm 1/E7 T-Cell Receptor (TCR) T Cell Therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>E7 TCR T Cell Therapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>E7 T-Cell Receptor (TCR)</intervention_name>
    <description>Patients will receive up to 3x10^10 E7 T-Cell Receptor (TCR) T cells (i.e. TCR+ cells).</description>
    <arm_group_label>Arm 1/E7 T-Cell Receptor (TCR) T Cell Therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -INCLUSION CRITERIA:&#xD;
&#xD;
          1. Participants with histologically or cytologically confirmed carcinoma of the cervix&#xD;
             that has not been treated, with clinical staging as follows:&#xD;
&#xD;
               -  Lead-in safety cohort: FIGO (International Federation of Gynecology and&#xD;
                  Obstetrics) stage IIIC-IVA (2018 International FIGO Staging System)&#xD;
&#xD;
               -  After lead-in safety cohort: FIGO stage IIB-IVA (2018 International FIGO Staging&#xD;
                  System)&#xD;
&#xD;
          2. Human papillomavirus 16 (HPV16+) tumor and HLA-A*02:01+ Human leukocyte antigen (HLA)&#xD;
             type. Note: HLA-A*02 is also acceptable for enrollment but not for treatment.&#xD;
&#xD;
          3. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1&#xD;
             criteria or Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST)&#xD;
             (if not eligible by RECIST 1.1).&#xD;
&#xD;
          4. Age 18 years. Because no dosing or adverse event data are currently available on the&#xD;
             use of E7 TCR T cells in participants &lt;18 years of age, children are excluded from&#xD;
             this study. Note: This age range is consistent with the age of participants with the&#xD;
             disease being studied.&#xD;
&#xD;
          5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.&#xD;
&#xD;
          6. Women of child-bearing potential must have a negative pregnancy test because E7 TCR T&#xD;
             cells have unknown potential for teratogenic or abortifacient effects. Women of child-&#xD;
             bearing potential are defined as all women who are not post-menopausal or who have not&#xD;
             had a hysterectomy. Note: Postmenopausal will be defined in this study as women over&#xD;
             the age of 55 who have not had a menstrual period in at least 1 year.&#xD;
&#xD;
          7. The effects of E7 TCR T cells on the developing human fetus are unknown. For this&#xD;
             reason and because the chemotherapy agents used in this trial are known to be&#xD;
             teratogenic, women of child-bearing potential must agree to use adequate contraception&#xD;
             (e.g., intrauterine device, hormonal or barrier method of birth control; abstinence;&#xD;
             tubal ligation or vasectomy) prior to study entry and for four months after treatment.&#xD;
             Should a woman become pregnant or suspect she is pregnant while she is participating&#xD;
             in this study, she should inform her treating physician immediately.&#xD;
&#xD;
          8. Seronegative for HIV (human immunodeficiency virus) antibody. The experimental&#xD;
             treatment being evaluated in this protocol depends on an intact immune system.&#xD;
             Participants who are HIV seropositive can have decreased immune-competence and thus be&#xD;
             less responsive to the experimental treatment.&#xD;
&#xD;
          9. Seronegative for hepatitis B antigen and hepatitis C antibody. If hepatitis C antibody&#xD;
             test is positive, then the participant must be tested for the presence of antigen by&#xD;
             Reverse transcription polymerase chain reaction (RT-PCR) and be hepatitis C Virus&#xD;
             (HCV) ribonucleic acid (RNA) negative.&#xD;
&#xD;
         10. Must be willing to participate in Gene Therapy Long Term Follow up Protocol (20C0051),&#xD;
             which will follow participants for up to 15 years per Food and Drug Administration&#xD;
             (FDA) requirements.&#xD;
&#xD;
         11. Participants must have organ and marrow function as defined below:&#xD;
&#xD;
               -  leukocytes &gt;=3,000/mcL&#xD;
&#xD;
               -  absolute neutrophil count &gt;=1,500/mcL&#xD;
&#xD;
               -  platelets &gt;=100,000/mcL&#xD;
&#xD;
               -  hemoglobin &gt;=9.0 g/dL&#xD;
&#xD;
               -  total bilirubin within normal institutional limits except in participants with&#xD;
                  Gilbert's Syndrome who must have a total bilirubin &lt; 3.0 mg/dL&#xD;
&#xD;
               -  Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase&#xD;
                  (SGOT)/alanine aminotransferase (ALT) serum glutamate-pyruvate transaminase&#xD;
                  (SGPT) Serum ALT/AST &lt; 2.5X ULN&#xD;
&#xD;
               -  creatinine clearance Calculated creatinine clearance (CrCl) &gt;=50 mL/min/1.73 m^2&#xD;
                  for participants with creatinine levels above institutional normal (by the&#xD;
                  Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation)&#xD;
&#xD;
         12. Ability of subject to understand and the willingness to sign a written informed&#xD;
             consent document.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          1. Previous treatment for invasive cervical cancer including:&#xD;
&#xD;
               -  Chemotherapy or other systemic treatments&#xD;
&#xD;
               -  Radiation therapy&#xD;
&#xD;
               -  Hysterectomy (prior LEEP procedure or cone biopsy is allowed)&#xD;
&#xD;
          2. Participants who are receiving any other investigational agents.&#xD;
&#xD;
          3. History of severe allergic reactions attributed to compounds of similar chemical or&#xD;
             biologic composition to agents used in study.&#xD;
&#xD;
          4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations at the time of treatment that&#xD;
             would limit compliance with study requirements.&#xD;
&#xD;
          5. Because there is an unknown but potential risk for adverse events in nursing infants&#xD;
             secondary to treatment of the mother with E7 TCR T cells, breastfeeding should be&#xD;
             discontinued if the mother is treated with E7 TCR T cells. These potential risks may&#xD;
             also apply to other agents used in this study.&#xD;
&#xD;
          6. Participants with any form of systemic immunodeficiency, including acquired deficiency&#xD;
             such as HIV or primary immunodeficiency such as Severe Combined Immunodeficiency&#xD;
             Disease, are ineligible. The experimental treatment being evaluated in this protocol&#xD;
             depends on an intact immune system. Participants who have decreased immune competence&#xD;
             may be less responsive to the treatment.&#xD;
&#xD;
          7. Participants on immunosuppressive drugs including corticosteroids.&#xD;
&#xD;
          8. Participants with autoimmune diseases such as Crohn's disease, ulcerative colitis,&#xD;
             rheumatoid arthritis, autoimmune hepatitis, autoimmune pancreatitis, or systemic lupus&#xD;
             erythematosus. Hypothyroidism, vitiligo and other minor autoimmune disorders are not&#xD;
             exclusionary.&#xD;
&#xD;
          9. Participants with a second invasive malignancy requiring treatment within the last 2&#xD;
             years are not eligible with the following exceptions:&#xD;
&#xD;
               -  Ductal carcinoma in situ (DCIS) of the breast&#xD;
&#xD;
               -  Cutaneous skin cancers requiring only local excision&#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_official>
    <last_name>Scott M Norberg, D.O.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Cancer Institute (NCI)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2020-C-0116.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>July 16, 2020</study_first_submitted>
  <study_first_submitted_qc>July 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <results_first_submitted>November 9, 2021</results_first_submitted>
  <results_first_submitted_qc>November 9, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">December 8, 2021</results_first_posted>
  <last_update_submitted>December 7, 2021</last_update_submitted>
  <last_update_submitted_qc>December 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 15, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Cancer Institute (NCI)</investigator_affiliation>
    <investigator_full_name>Scott Norberg, D.O.</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>T Cell Receptor</keyword>
  <keyword>Immunotherapy</keyword>
  <keyword>Aldesleukin</keyword>
  <keyword>Cyclophosphamide</keyword>
  <keyword>Fludarabine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Uterine Cervical Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 4, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/51/NCT04476251/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form: Screening Consent</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 2, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/51/NCT04476251/ICF_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form: Affected Patient Consent</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 2, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/51/NCT04476251/ICF_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Arm 1/E7 T-Cell Receptor (TCR) T Cell Therapy</title>
          <description>E7 TCR T Cell Therapy&#xD;
E7 TCR: Patients will receive up to 3x10^10 E7 T-Cell Receptor (TCR) T cells (i.e. TCR+ cells).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Not treated</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Arm 1/E7 T-Cell Receptor (TCR) T Cell Therapy</title>
          <description>E7 TCR T Cell Therapy&#xD;
E7 TCR: Patients will receive up to 3x10^10 E7 T-Cell Receptor (TCR) T cells (i.e. TCR+ cells).</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="1"/>
          </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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18" spread="0"/>
                  </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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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="0"/>
                  </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>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Fraction of Participants for Whom E7 T-Cell Receptor (TCR) Induction Therapy is Feasible in Participants With Cervical Cancer</title>
        <description>The Fraction of participants for whom E7 T-Cell Receptor (TCR) induction therapy is feasible in participants with cervical cancer</description>
        <time_frame>6 months</time_frame>
        <population>This outcome measure was not done due to multiple logistical challenges. One participant was enrolled but not treated.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1/E7 T-Cell Receptor (TCR) T Cell Therapy</title>
            <description>E7 TCR T Cell Therapy&#xD;
E7 TCR: Patients will receive up to 3x10^10 E7 T-Cell Receptor (TCR) T cells (i.e. TCR+ cells).</description>
          </group>
        </group_list>
        <measure>
          <title>The Fraction of Participants for Whom E7 T-Cell Receptor (TCR) Induction Therapy is Feasible in Participants With Cervical Cancer</title>
          <description>The Fraction of participants for whom E7 T-Cell Receptor (TCR) induction therapy is feasible in participants with cervical cancer</description>
          <population>This outcome measure was not done due to multiple logistical challenges. One participant was enrolled but not treated.</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>
        <type>Secondary</type>
        <title>Fraction of Participants With Relapse-free Survival at 2 Years and 5 Years Following Definitive Standard of Care Therapy</title>
        <description>Fraction of participants with relapse-free survival at 2 years and 5 years estimated from a Kaplan-Meier curve of relapsed free survival following definitive standard of care therapy who achieve a success. Relapsed free survival is defined as the time from date on study to date of relapse of disease.</description>
        <time_frame>2 yrs and 5 yrs</time_frame>
        <population>This outcome measure was not done due to multiple logistical challenges. One participant was enrolled but not treated.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1/E7 T-Cell Receptor (TCR) T Cell Therapy</title>
            <description>E7 TCR T Cell Therapy&#xD;
E7 TCR: Patients will receive up to 3x10^10 E7 T-Cell Receptor (TCR) T cells (i.e. TCR+ cells).</description>
          </group>
        </group_list>
        <measure>
          <title>Fraction of Participants With Relapse-free Survival at 2 Years and 5 Years Following Definitive Standard of Care Therapy</title>
          <description>Fraction of participants with relapse-free survival at 2 years and 5 years estimated from a Kaplan-Meier curve of relapsed free survival following definitive standard of care therapy who achieve a success. Relapsed free survival is defined as the time from date on study to date of relapse of disease.</description>
          <population>This outcome measure was not done due to multiple logistical challenges. One participant was enrolled but not treated.</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>
        <type>Secondary</type>
        <title>Fraction of Participants With Grade 1-5 Adverse Events</title>
        <description>To evaluate the safety of E7 induction therapy, the types and grades of toxicity obtained will be reported. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse event.</description>
        <time_frame>1 year</time_frame>
        <population>This outcome measure was not done due to multiple logistical challenges. One participant was enrolled but not treated.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1/E7 T-Cell Receptor (TCR) T Cell Therapy</title>
            <description>E7 TCR T Cell Therapy&#xD;
E7 TCR: Patients will receive up to 3x10^10 E7 T-Cell Receptor (TCR) T cells (i.e. TCR+ cells).</description>
          </group>
        </group_list>
        <measure>
          <title>Fraction of Participants With Grade 1-5 Adverse Events</title>
          <description>To evaluate the safety of E7 induction therapy, the types and grades of toxicity obtained will be reported. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse event.</description>
          <population>This outcome measure was not done due to multiple logistical challenges. One participant was enrolled but not treated.</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>
        <type>Secondary</type>
        <title>Percentage of E7 T-Cell Receptor (TCR)T Cells Following Completion of Chemoradiation</title>
        <description>Percentage of E7 T-Cell Receptor (TCR)T cells following completion of chemoradiation</description>
        <time_frame>1 year</time_frame>
        <population>This outcome measure was not done due to multiple logistical challenges. One participant was enrolled but not treated.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1/E7 T-Cell Receptor (TCR) T Cell Therapy</title>
            <description>E7 TCR T Cell Therapy&#xD;
E7 TCR: Patients will receive up to 3x10^10 E7 T-Cell Receptor (TCR) T cells (i.e. TCR+ cells).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of E7 T-Cell Receptor (TCR)T Cells Following Completion of Chemoradiation</title>
          <description>Percentage of E7 T-Cell Receptor (TCR)T cells following completion of chemoradiation</description>
          <population>This outcome measure was not done due to multiple logistical challenges. One participant was enrolled but not treated.</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>
        <type>Secondary</type>
        <title>Fraction of Participants Who Achieve an Objective Response (Partial Response + Complete Response) Following E7 T-Cell Receptor (TCR) T Cell Induction Therapy</title>
        <description>Fraction of participants who achieve an objective response (Partial Response + Complete Response) following E7 induction therapy will be reported. Response may be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response is disappearance of all target lesions. Partial Response is at least a 30% decrease in the sum of the diameters of target lesion; and/or Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST). Complete Metabolic Response is complete resolution of F-fluorodeoxyglucose (FDG) uptake in all lesions, and Partial Metabolic Response is ≥ 30% reduction of the SUL (lean body mass corrected standard uptake value) peak and an absolute drop of 0.8 SULpeak units.</description>
        <time_frame>1 year</time_frame>
        <population>This outcome measure was not done due to multiple logistical challenges. One participant was enrolled but not treated.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1/E7 T-Cell Receptor (TCR) T Cell Therapy</title>
            <description>E7 TCR T Cell Therapy&#xD;
E7 TCR: Patients will receive up to 3x10^10 E7 T-Cell Receptor (TCR) T cells (i.e. TCR+ cells).</description>
          </group>
        </group_list>
        <measure>
          <title>Fraction of Participants Who Achieve an Objective Response (Partial Response + Complete Response) Following E7 T-Cell Receptor (TCR) T Cell Induction Therapy</title>
          <description>Fraction of participants who achieve an objective response (Partial Response + Complete Response) following E7 induction therapy will be reported. Response may be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response is disappearance of all target lesions. Partial Response is at least a 30% decrease in the sum of the diameters of target lesion; and/or Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST). Complete Metabolic Response is complete resolution of F-fluorodeoxyglucose (FDG) uptake in all lesions, and Partial Metabolic Response is ≥ 30% reduction of the SUL (lean body mass corrected standard uptake value) peak and an absolute drop of 0.8 SULpeak units.</description>
          <population>This outcome measure was not done due to multiple logistical challenges. One participant was enrolled but not treated.</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>
        <type>Other Pre-specified</type>
        <title>Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)</title>
        <description>Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.</description>
        <time_frame>Date treatment consent signed to date off study, approximately 20 days.</time_frame>
        <population>This outcome measure was not done due to multiple logistical challenges. One participant was enrolled but not treated.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1/E7 T-Cell Receptor (TCR) T Cell Therapy</title>
            <description>E7 TCR T Cell Therapy&#xD;
E7 TCR: Patients will receive up to 3x10^10 E7 T-Cell Receptor (TCR) T cells (i.e. TCR+ cells).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)</title>
          <description>Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.</description>
          <population>This outcome measure was not done due to multiple logistical challenges. One participant was enrolled but not treated.</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>Date treatment consent signed to date off study, approximately 20 days.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Arm 1/E7 T-Cell Receptor (TCR) T Cell Therapy</title>
          <description>E7 TCR T Cell Therapy&#xD;
E7 TCR: Patients will receive up to 3x10^10 E7 T-Cell Receptor (TCR) T cells (i.e. TCR+ cells).</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
              </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 NOT 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>Scott M. Norberg D.O.</name_or_title>
      <organization>National Cancer Institute</organization>
      <phone>301-275-9668</phone>
      <email>scott.norberg@nih.gov</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/NCT04476251
org study id: 200116
secondary id: 20-C-0116
nct id: NCT04476251
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Background:

      More than 12,000 cases of cervical cancer are diagnosed in the United States each year. A new
      therapy has been developed that involves taking white blood cells from a person, genetically
      modifying the cells in a lab so they recognize cancer, and then giving the cells back to the
      person. Researchers want to see if this therapy can help people with cervical cancer.

      Objective:

      To find out if people with Stage IIB-IVA cervical cancer can safely be given E7 T-cell
      receptor (TCR) T cells before they get standard treatment.

      Eligibility:

      People age 18 and older who have Stage IIB-IVA cervical cancer

      Design:

      Participants will be screened under a separate protocol. Tests will include:

        -  Physical exam

        -  Medicine review

        -  Blood tests

        -  Pregnancy test (if needed)

        -  Vein assessment

        -  Tumor sample or biopsy

        -  Electrocardiogram (to record the hearts electrical activity)

        -  Imaging scans, x-rays, and/or endoscopy

        -  Heart and/or lung tests.

      Some screening tests will be repeated during the study.

      Participants will undergo leukapheresis. For this, blood is removed through a needle in the
      arm. A machine removes the white blood cells. The rest of the blood is returned through a
      needle in the other arm. Participants may need to have a large catheter inserted into a vein.

      Participants will stay at the hospital for 2-3 weeks. They will get chemotherapy drugs. They
      will get the E7 TCR T cells as an intravenous infusion. They will get the drug aldesleukin.

      Participants will visit the National Institutes of Health (NIH) 3 and 6 weeks after
      treatment. They will be contacted yearly for 5 years. They will be asked to participate in
      long-term follow-up for 15 years....
Background:

        -  Cervical cancer is the third most common cause of death among women with gynecologic
           cancers in the United States. Worldwide, cervical cancer accounts for nearly 300,000
           deaths annually.

        -  Virtually all cases of cervical cancer result from chronic infection with high-risk
           human papillomavirus (HPV), the most common type being HPV16.

        -  The treatment of locally advanced cervical cancer consists of chemoradiation +/-
           extended field radiation therapy. Participants with International Federation of
           Gynecology and Obstetrics (FIGO) (revised 2018) stage III-IVA have the worse prognosis
           with approximately 50% of the participants dying from their disease within 5 years.

        -  Induction chemotherapy is an active area of study in this type of cancer. The aim of
           induction therapy is to reduce the risk of disease recurrence and improve overall
           survival.

        -  E7 T-cell receptor (TCR) T cells, administered as a single infusion, have demonstrated
           safety and clinical activity in advanced, treatment-refractory metastatic HPV+ cancers.

      Objectives:

      -To determine the feasibility of induction E7 TCR T cell therapy for FIGO (2018) stage
      IIB-IVA, HPV16+ cervical cancer

      Eligibility:

        -  Participants greater than or equal to 18 years old with FIGO (2018) stage IIB-IVA
           cervical cancer.

        -  The cancer must be human papillomavirus 16 (HPV16+) and participant must be
           HLA-A*02:01+.

        -  Participants must be treatment-naive (i.e., no prior local or systemic treatment,
           including radiation; prior loop electrosurgical excision procedure (LEEP) procedure or
           cone biopsy is allowed).

      Design:

        -  This is a single arm, pilot study, testing the feasibility of induction E7 TCR T cell
           therapy.

        -  Participants will receive a conditioning regimen of cyclophosphamide and fludarabine, a
           single infusion of E7 TCR T cells, and systemic aldesleukin.

        -  Participants will be referred for standard of care definitive therapy (i.e.,
           chemoradiation +/- extended field radiation therapy) within 6 weeks after infusion of E7
           TCR T cells.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The Fraction of Participants for Whom E7 T-Cell Receptor (TCR) Induction Therapy is Feasible in Participants With Cervical Cancer
time frame: 6 months
description: The Fraction of participants for whom E7 T-Cell Receptor (TCR) induction therapy is feasible in participants with cervical cancer
measure: Fraction of Participants With Relapse-free Survival at 2 Years and 5 Years Following Definitive Standard of Care Therapy
time frame: 2 yrs and 5 yrs
description: Fraction of participants with relapse-free survival at 2 years and 5 years estimated from a Kaplan-Meier curve of relapsed free survival following definitive standard of care therapy who achieve a success. Relapsed free survival is defined as the time from date on study to date of relapse of disease.
measure: Fraction of Participants With Grade 1-5 Adverse Events
time frame: 1 year
description: To evaluate the safety of E7 induction therapy, the types and grades of toxicity obtained will be reported. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse event.
measure: Percentage of E7 T-Cell Receptor (TCR)T Cells Following Completion of Chemoradiation
time frame: 1 year
description: Percentage of E7 T-Cell Receptor (TCR)T cells following completion of chemoradiation
measure: Fraction of Participants Who Achieve an Objective Response (Partial Response + Complete Response) Following E7 T-Cell Receptor (TCR) T Cell Induction Therapy
time frame: 1 year
description: Fraction of participants who achieve an objective response (Partial Response + Complete Response) following E7 induction therapy will be reported. Response may be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response is disappearance of all target lesions. Partial Response is at least a 30% decrease in the sum of the diameters of target lesion; and/or Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST). Complete Metabolic Response is complete resolution of F-fluorodeoxyglucose (FDG) uptake in all lesions, and Partial Metabolic Response is ≥ 30% reduction of the SUL (lean body mass corrected standard uptake value) peak and an absolute drop of 0.8 SULpeak units.
measure: Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
time frame: Date treatment consent signed to date off study, approximately 20 days.
description: Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
arm group label: Arm 1/E7 T-Cell Receptor (TCR) T Cell Therapy
arm group type: Experimental
description: E7 TCR T Cell Therapy
intervention type: Biological
intervention name: E7 T-Cell Receptor (TCR)
description: Patients will receive up to 3x10^10 E7 T-Cell Receptor (TCR) T cells (i.e. TCR+ cells).
arm group label: Arm 1/E7 T-Cell Receptor (TCR) T Cell Therapy
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Scott M Norberg, D.O.
role: Principal Investigator
affiliation: National Cancer Institute (NCI)
facility: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2020-C-0116.html
description: NIH Clinical Center Detailed Web Page
responsible party type: Principal Investigator
investigator affiliation: National Cancer Institute (NCI)
investigator full name: Scott Norberg, D.O.
investigator title: Principal Investigator
mesh term: Uterine Cervical Neoplasms
sharing ipd: No
provided document: 
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 