<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/NCT03808168</url>
  </required_header>
  <id_info>
    <org_study_id>STU 032017-028</org_study_id>
    <nct_id>NCT03808168</nct_id>
  </id_info>
  <brief_title>Nivolumab Based Immunotherapy for Treatment of High Grade Cervical Dysplasia</brief_title>
  <official_title>Phase II Trial of Nivolumab Based Immunotherapy for the Treatment of High-Grade Cervical Dysplasia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Texas Southwestern Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Texas Southwestern Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study design is a phase II interventional trial for women with biopsy proven high-grade&#xD;
      cervical dysplasia. The study is an open label study and randomized. The study will have two&#xD;
      arms. Patients will be randomized to both arms.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      High-grade cervical dysplasia (cervical intraepithelial neoplasia (CIN) II/III), is both&#xD;
      detectable and quantifiable, which presents many opportunities for evaluation or early&#xD;
      treatment, intervention and eventually, for cancer prevention. High-grade dysplasia is&#xD;
      typically detected during cervical cancer screening with a pap smear. To determine the&#xD;
      pathologic response rate of high grade cervical dysplasia with PD-1 checkpoint modulation&#xD;
      with Nivolumab.This is a randomized phase II trial with two experimental arms (1 dose of&#xD;
      nivolumab and 3 doses of nivolumab).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    FDA has withdrawn the IND application- requesting protocol changes&#xD;
  </why_stopped>
  <start_date type="Anticipated">January 15, 2019</start_date>
  <completion_date type="Anticipated">June 1, 2020</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of regression on high grade dysplasia lesions</measure>
    <time_frame>15 weeks after the beginning of immunotherapy</time_frame>
    <description>The endpoints of the current study will be to determine the rate of spontaneous regression on high grade dysplasia lesions</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Cervix Uteri--Diseases</condition>
  <arm_group>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Nivolumab, 3 mg/kg Iv, day 1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Nivolumab, 3 mg/kg IV, days 1, 15, 29</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>Protocol dose: 3mg/kg mg as a 30-minute IV infusion on Day 1 (Arm I) or Days 1, 15, 29 (Arm II).</description>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_label>Arm 2</arm_group_label>
    <other_name>Opdivo, BMS-936558, MDX1106</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult female subjects (age 18 years or older)&#xD;
&#xD;
          -  Performance status ECOG 0-1&#xD;
&#xD;
          -  All patients must have cervical biopsies demonstrating high-grade cervical dysplasia.&#xD;
&#xD;
          -  All patients must have a satisfactory colposcopy with visualization of the entire&#xD;
             squamo-columnar junction&#xD;
&#xD;
          -  All patients must be candidates for a cervical conization procedure or LEEP procedure&#xD;
&#xD;
          -  The patient is able and willing to comply with study procedures, and signed and dated&#xD;
             informed consent is obtained before any study-related procedure is performed&#xD;
&#xD;
          -  Negative screening test results for hepatitis B, hepatitis C, and human&#xD;
             immunodeficiency virus&#xD;
&#xD;
          -  At least six weeks must have elapsed from any prior chemotherapy, radiation therapy or&#xD;
             immunotherapy&#xD;
&#xD;
          -  Patients must have adequate:&#xD;
&#xD;
               -  Bone marrow function: Absolute neutrophil count (ANC) greater than or equal to&#xD;
                  1,500/mcl. Platelets greater than or equal to100, 000/mcl. Hemoglobin &gt; 9 gm/dL.&#xD;
&#xD;
               -  Renal function: creatinine less than or equal to institutional upper limit normal&#xD;
                  (ULN) or calculated creatinine clearance (Cockcroft-Gault) ≥ 50 ml/min.&#xD;
&#xD;
               -  Serum creatinine &lt;/= 1.5xULN or creatinine clearance (CrCl) &gt;/=50 mL/min (using&#xD;
                  the Cockcroft-Gault formula)&#xD;
&#xD;
               -  Female CrCl = (140-age in years) x weight in kg x 0.85 72 x serum creatinine in&#xD;
                  mg/dL&#xD;
&#xD;
               -  Metabolic function: Calcium, Magnesium, Phosphate, and Potassium levels within&#xD;
                  institutional normal limits.&#xD;
&#xD;
               -  Hepatic function: Bilirubin less than or equal to 1.5 x ULN. AST and ALT less&#xD;
                  than or equal to 3 ULN and alkaline phosphatase less than or equal to 2.5 x ULN.&#xD;
&#xD;
          -  Patients must have signed an approved informed consent and authorization permitting&#xD;
             release of personal health information.&#xD;
&#xD;
          -  Patients of childbearing potential must have a negative serum pregnancy test prior to&#xD;
             the study entry and be practicing an effective form of contraception. The effects of&#xD;
             Nivolumab on the developing human fetus are unknown. For this reason and because other&#xD;
             therapeutic agents or modalities used in this trial are known to be teratogenic, women&#xD;
             of child-bearing potential must agree to use adequate contraception (hormonal or&#xD;
             barrier method of birth control; abstinence) prior to study entry, through the&#xD;
             duration of study participation and for a period of 5 months after the last dose of&#xD;
             nivolumab. Should a woman become pregnant or suspect she is pregnant while&#xD;
             participating in this study, she should inform her treating physician immediately.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The patient is lactating or pregnant&#xD;
&#xD;
          -  The colposcopy is inadequate; the entire transformation zone is not visualized and&#xD;
             endocervical curettage is positive for high-grade dysplasia&#xD;
&#xD;
          -  Clinical concern for invasive cervical cancer&#xD;
&#xD;
          -  Patients must not have received any prior oncology vaccine therapy&#xD;
&#xD;
          -  Intercurrent medical illnesses that would impair patient tolerance to participation&#xD;
&#xD;
          -  Any concurrent medical condition requiring the use of systemic steroids is not&#xD;
             permitted (the use of inhaled or topic steroids is permitted)&#xD;
&#xD;
          -  Concurrent treatment with chemotherapy, radiation therapy or immunotherapy for&#xD;
             intercurrent illnesses&#xD;
&#xD;
          -  Any serious or uncontrolled medical disorder that, in the opinion of the investigator,&#xD;
             may increase the risk associated with study participation or study drug&#xD;
             administration, impair the ability of the subject to receive protocol therapy, or&#xD;
             interfere with the interpretation of study results;&#xD;
&#xD;
          -  Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody or any&#xD;
             other antibody or drug specifically targeting T-cell co-stimulation or immune&#xD;
             checkpoint pathways;&#xD;
&#xD;
          -  Subjects with an active, known or suspected autoimmune disease. Subjects with type I&#xD;
             diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders&#xD;
             (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or&#xD;
             conditions not expected to recur in the absence of an external trigger are permitted&#xD;
             to enroll;&#xD;
&#xD;
          -  Subjects with interstitial lung disease that is symptomatic or may interfere with the&#xD;
             detection or management of suspected drug-related pulmonary toxicity&#xD;
&#xD;
          -  Subjects with history of life-threatening toxicity, including hypersensitivity&#xD;
             reaction, related to prior immunoglobulin treatment for another condition or any other&#xD;
             study drug component.&#xD;
&#xD;
          -  History or evidence upon physical/neurological examination of other central nervous&#xD;
             system condition (e.g., seizures, abscess) unrelated to cancer, unless adequately&#xD;
             controlled by medication or considered not potentially interfering with protocol&#xD;
             treatment;&#xD;
&#xD;
          -  Surgical procedure &lt;7 days prior to study treatment, vascular access device no&#xD;
             restriction;&#xD;
&#xD;
          -  Subjects unable (e.g., due to pacemaker or ICD device) or unwilling to have a&#xD;
             contrast-enhanced MRI of the head;&#xD;
&#xD;
          -  History of allergy or hypersensitivity to study drug components&#xD;
&#xD;
          -  Subjects with a condition requiring systemic treatment with either corticosteroids (&gt;&#xD;
             10 mg daily prednisone equivalents) or other immunosuppressive medications within 14&#xD;
             days of study drug administration. Inhaled or topical steroids, and adrenal&#xD;
             replacement doses &gt; 10 mg daily prednisone equivalents are permitted in the absence of&#xD;
             active autoimmune disease.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jayanthi Lea, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Univeristy of Texas Southwestern Medical Center</affiliation>
  </overall_official>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 15, 2019</study_first_submitted>
  <study_first_submitted_qc>January 15, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 17, 2019</study_first_posted>
  <last_update_submitted>January 17, 2019</last_update_submitted>
  <last_update_submitted_qc>January 17, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Uterine Cervical Dysplasia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nivolumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03808168
org study id: STU 032017-028
nct id: NCT03808168
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The study design is a phase II interventional trial for women with biopsy proven high-grade
      cervical dysplasia. The study is an open label study and randomized. The study will have two
      arms. Patients will be randomized to both arms.
High-grade cervical dysplasia (cervical intraepithelial neoplasia (CIN) II/III), is both
      detectable and quantifiable, which presents many opportunities for evaluation or early
      treatment, intervention and eventually, for cancer prevention. High-grade dysplasia is
      typically detected during cervical cancer screening with a pap smear. To determine the
      pathologic response rate of high grade cervical dysplasia with PD-1 checkpoint modulation
      with Nivolumab.This is a randomized phase II trial with two experimental arms (1 dose of
      nivolumab and 3 doses of nivolumab).
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of regression on high grade dysplasia lesions
time frame: 15 weeks after the beginning of immunotherapy
description: The endpoints of the current study will be to determine the rate of spontaneous regression on high grade dysplasia lesions
arm group label: Arm 1
arm group type: Active Comparator
description: Nivolumab, 3 mg/kg Iv, day 1
arm group label: Arm 2
arm group type: Active Comparator
description: Nivolumab, 3 mg/kg IV, days 1, 15, 29
intervention type: Drug
intervention name: Nivolumab
description: Protocol dose: 3mg/kg mg as a 30-minute IV infusion on Day 1 (Arm I) or Days 1, 15, 29 (Arm II).
arm group label: Arm 1
arm group label: Arm 2
other name: Opdivo, BMS-936558, MDX1106
criteria: 
gender: Female
gender based: Yes
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jayanthi Lea, MD
role: Principal Investigator
affiliation: Univeristy of Texas Southwestern Medical Center
responsible party type: Sponsor
mesh term: Uterine Cervical Dysplasia
mesh term: Nivolumab
sharing ipd: No