<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/NCT01711515</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2012-01733</org_study_id>
    <secondary_id>NCI-2012-01733</secondary_id>
    <secondary_id>GOG-PIS1102</secondary_id>
    <secondary_id>GOG-9929</secondary_id>
    <secondary_id>GOG-9929</secondary_id>
    <secondary_id>GOG-9929</secondary_id>
    <secondary_id>U10CA180830</secondary_id>
    <secondary_id>U10CA180868</secondary_id>
    <secondary_id>U10CA027469</secondary_id>
    <nct_id>NCT01711515</nct_id>
  </id_info>
  <brief_title>Chemoradiation Therapy and Ipilimumab in Treating Patients With Stages IB2-IIB or IIIB-IVA Cervical Cancer</brief_title>
  <official_title>A Phase I Trial of Sequential Ipilimumab After Chemoradiation for the Primary Treatment of Patients With Locally Advanced Cervical Cancer Stages IB2/IIA With Positive Para-Aortic Lymph Nodes Only and Stage IIB/IIIB/IVA With Positive Lymph Nodes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>NRG Oncology</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>National Cancer Institute (NCI)</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I trial studies the side effects and best dose of ipilimumab when given after&#xD;
      chemoradiation therapy in treating patients with stages IB2-IIB or IIIB-IVA cervical cancer.&#xD;
      Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of&#xD;
      tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them&#xD;
      from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink&#xD;
      tumors. Monoclonal antibodies, such as ipilimumab, may find tumor cells and help carry&#xD;
      tumor-killing substances to them. Giving ipilimumab together with chemoradiation therapy may&#xD;
      be a better way treat cervical cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To estimate the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of&#xD;
      adjuvant ipilimumab following concurrent weekly cisplatin and extended field radiation in&#xD;
      women with newly diagnosed locally advanced cervical cancer stage IB2/ IIA with-positive&#xD;
      para-aortic lymph nodes only and stage IIB/IIIB/IVA with positive lymph nodes.&#xD;
&#xD;
      II. To determine the feasibility of the treatment regimen over the four cycles of adjuvant&#xD;
      ipilimumab once the MTD is estimated.&#xD;
&#xD;
      III. To assess the toxicities of the treatment regimen per the National Cancer Institute&#xD;
      (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To examine progression free survival for 1 year after study completion. II. To determine&#xD;
      site of recurrence, loco-regional versus distant, for one year after completion of therapy.&#xD;
&#xD;
      III. To estimate the frequency of chronic toxicities experienced within one year after&#xD;
      completion of therapy.&#xD;
&#xD;
      TERTIARY OBJECTIVES:&#xD;
&#xD;
      I. To enumerate the human papillomavirus (HPV)-subtype-specific T-cells and characterize the&#xD;
      kinetics of HPV-subtype-specific T-cell expansion associated with chemoradiation and&#xD;
      ipilimumab treatment.&#xD;
&#xD;
      II. To characterize the association between differential expression of immune markers on&#xD;
      leukocytes from human leukocyte antigen (HLA)-A*0201 patients and response to chemoradiation&#xD;
      and ipilimumab treatment.&#xD;
&#xD;
      III. To assess qualitative changes in maximum standardized uptake value (SUVmax) from&#xD;
      positron emission tomography (PET)/computed tomography (CT) after treatment with&#xD;
      chemoradiation and ipilimumab.&#xD;
&#xD;
      IV. To bank residual plasma (obtained from leukocyte processing) for future research.&#xD;
&#xD;
      OUTLINE: This is a dose-escalation study of ipilimumab.&#xD;
&#xD;
      Patients receive cisplatin intravenously (IV) over 1 hour on days 1, 8, 15, 22, 29, and 36,&#xD;
      undergo external beam radiation therapy 5 days a week for 6 weeks, and then undergo&#xD;
      intracavitary brachytherapy for approximately 2 weeks. Within 2 weeks, patients receive&#xD;
      ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 3 months for 1 year and&#xD;
      then every 6 months for 1 year.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2012</start_date>
  <completion_date type="Actual">July 17, 2020</completion_date>
  <primary_completion_date type="Actual">February 9, 2017</primary_completion_date>
  <phase>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>DLTs occurring during adjuvant ipilimumab in the dose escalation phase</measure>
    <time_frame>During first 2 courses of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>DLTs occurring in the feasibility phase</measure>
    <time_frame>Over 4 courses of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Toxicities as assessed by CTCAE version 4</measure>
    <time_frame>Up to 2 years post-treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Response rate in patients enrolled with measurable disease assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1</measure>
    <time_frame>Up to 2 years post-treatment</time_frame>
    <description>Relationships of translational research endpoints to response will be explored if practical.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>From time of study entry to time of progression or death, whichever occurs first, assessed up to 1 year post-treatment</time_frame>
    <description>Will be summarized using Kaplan-Meier plots. Relationships of translational research endpoints to PFS will be explored if practical.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From time of study entry to time of death or the date the patient was last confirmed to be alive, assessed up to 1 year post-treatment</time_frame>
    <description>Will be summarized using Kaplan-Meier plots.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Location of recurrence (loco-regional versus distant)</measure>
    <time_frame>Up to 1 year post-treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Chronic toxicities experienced within one year of completion of therapy</measure>
    <time_frame>Up to 1 year post-treatment</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Enumeration of HPV-specific T-cells</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Summary statistics (and graphs) of translational research endpoints will be done by dose level. Relationships of these endpoints to response and PFS will be explored if practical.</description>
  </other_outcome>
  <other_outcome>
    <measure>Kinetics of HPV-specific T-cell expansion</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Summary statistics (and graphs) of translational research endpoints will be done by dose level. Relationships of these endpoints to response and PFS will be explored if practical.</description>
  </other_outcome>
  <other_outcome>
    <measure>Characterization of differential activated T-cell responses based on HLA-subtype A*0201</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Summary statistics (and graphs) of translational research endpoints will be done by dose level. Relationships of these endpoints to response and PFS will be explored if practical.</description>
  </other_outcome>
  <other_outcome>
    <measure>Measurable parameters from the fludeoxyglucose F 18 (FDG)-PET/CT, including SUVmax of the primary tumor, metabolic tumor volume (MTV) if available, the presence of abnormal FDG uptake within lymph nodes</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Summary statistics (and graphs) of translational research endpoints will be done by dose level. Relationships of these endpoints to response and PFS will be explored if practical. Within-patient changes in the FDG-PET/CT SUVmax and MTV (if available) will be examined.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Cervical Adenocarcinoma</condition>
  <condition>Cervical Adenosquamous Carcinoma</condition>
  <condition>Cervical Squamous Cell Carcinoma, Not Otherwise Specified</condition>
  <condition>Stage IB2 Cervical Cancer AJCC v6 and v7</condition>
  <condition>Stage II Cervical Cancer AJCC v7</condition>
  <condition>Stage IIA Cervical Cancer AJCC v7</condition>
  <condition>Stage IIB Cervical Cancer AJCC v6 and v7</condition>
  <condition>Stage IIIB Cervical Cancer AJCC v6 and v7</condition>
  <condition>Stage IVA Cervical Cancer AJCC v6 and v7</condition>
  <arm_group>
    <arm_group_label>Treatment (cisplatin, radiation therapy, and ipilimumab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive cisplatin IV over 1 hour on days 1, 8, 15, 22, 29, and 36, undergo extended beam radiation therapy 5 days a week for 6 weeks, and then undergo intracavitary brachytherapy for approximately 2 weeks. Within 2 weeks, patients receive ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (cisplatin, radiation therapy, and ipilimumab)</arm_group_label>
    <other_name>Abiplatin</other_name>
    <other_name>Blastolem</other_name>
    <other_name>Briplatin</other_name>
    <other_name>CDDP</other_name>
    <other_name>Cis-diammine-dichloroplatinum</other_name>
    <other_name>Cis-diamminedichloridoplatinum</other_name>
    <other_name>Cis-diamminedichloro Platinum (II)</other_name>
    <other_name>Cis-diamminedichloroplatinum</other_name>
    <other_name>Cis-dichloroammine Platinum (II)</other_name>
    <other_name>Cis-platinous Diamine Dichloride</other_name>
    <other_name>Cis-platinum</other_name>
    <other_name>Cis-platinum II</other_name>
    <other_name>Cis-platinum II Diamine Dichloride</other_name>
    <other_name>Cismaplat</other_name>
    <other_name>Cisplatina</other_name>
    <other_name>Cisplatinum</other_name>
    <other_name>Cisplatyl</other_name>
    <other_name>Citoplatino</other_name>
    <other_name>Citosin</other_name>
    <other_name>Cysplatyna</other_name>
    <other_name>DDP</other_name>
    <other_name>Lederplatin</other_name>
    <other_name>Metaplatin</other_name>
    <other_name>Neoplatin</other_name>
    <other_name>Peyrone''s Chloride</other_name>
    <other_name>Peyrone''s Salt</other_name>
    <other_name>Placis</other_name>
    <other_name>Plastistil</other_name>
    <other_name>Platamine</other_name>
    <other_name>Platiblastin</other_name>
    <other_name>Platiblastin-S</other_name>
    <other_name>Platinex</other_name>
    <other_name>Platinol</other_name>
    <other_name>Platinol- AQ</other_name>
    <other_name>Platinol-AQ</other_name>
    <other_name>Platinol-AQ VHA Plus</other_name>
    <other_name>Platinoxan</other_name>
    <other_name>Platinum</other_name>
    <other_name>Platinum Diamminodichloride</other_name>
    <other_name>Platiran</other_name>
    <other_name>Platistin</other_name>
    <other_name>Platosin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>External Beam Radiation Therapy</intervention_name>
    <description>Undergo external beam radiation therapy</description>
    <arm_group_label>Treatment (cisplatin, radiation therapy, and ipilimumab)</arm_group_label>
    <other_name>Definitive Radiation Therapy</other_name>
    <other_name>EBRT</other_name>
    <other_name>External Beam Radiation</other_name>
    <other_name>External Beam Radiotherapy</other_name>
    <other_name>External Beam RT</other_name>
    <other_name>external radiation</other_name>
    <other_name>External Radiation Therapy</other_name>
    <other_name>external-beam radiation</other_name>
    <other_name>Radiation, External Beam</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Internal Radiation Therapy</intervention_name>
    <description>Undergo intracavitary brachytherapy</description>
    <arm_group_label>Treatment (cisplatin, radiation therapy, and ipilimumab)</arm_group_label>
    <other_name>Brachytherapy</other_name>
    <other_name>Brachytherapy, NOS</other_name>
    <other_name>Internal Radiation</other_name>
    <other_name>Internal Radiation Brachytherapy</other_name>
    <other_name>Radiation Brachytherapy</other_name>
    <other_name>Radiation, Internal</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Ipilimumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (cisplatin, radiation therapy, and ipilimumab)</arm_group_label>
    <other_name>Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody</other_name>
    <other_name>BMS-734016</other_name>
    <other_name>MDX-010</other_name>
    <other_name>MDX-CTLA4</other_name>
    <other_name>Yervoy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (cisplatin, radiation therapy, and ipilimumab)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with histologically confirmed advanced cervical cancer (squamous cell&#xD;
             carcinoma, adenocarcinoma, and adenosquamous cell carcinoma): International Federation&#xD;
             of Gynecology and Obstetrics (FIGO) clinical stages IB2/IIA with positive para-aortic&#xD;
             lymph nodes or FIGO clinical stages IIB/IIIB/IVA with positive pelvic and/or&#xD;
             para-aortic lymph nodes; nodal status will be confirmed by PET/CT scan, fine needle&#xD;
             biopsy, extra peritoneal biopsy, laparoscopic biopsy or lymphadenectomy&#xD;
&#xD;
          -  Patients must have a Gynecologic Oncology Group (GOG) performance status of 0-1&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1,500/mcl&#xD;
&#xD;
          -  Platelets &gt;= 100,000/mcl&#xD;
&#xD;
          -  Creatinine =&lt; institutional upper limit normal (ULN); note: if creatinine &gt; ULN,&#xD;
             creatinine clearance must be &gt; 50 mL/min&#xD;
&#xD;
          -  Bilirubin =&lt; 1.5 x ULN&#xD;
&#xD;
          -  Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and&#xD;
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =&lt; 2.5 x&#xD;
             ULN&#xD;
&#xD;
          -  Alkaline phosphatase =&lt; 2.5 x ULN&#xD;
&#xD;
          -  Neuropathy (sensory and motor) =&lt; grade 1&#xD;
&#xD;
          -  Patients with ureteral obstruction (i.e., hydronephrosis identified on CT imaging)&#xD;
             must undergo stent or nephrostomy tube placement prior to study entry&#xD;
&#xD;
          -  Patients must meet the pre-entry requirements specified&#xD;
&#xD;
          -  Patients must have signed an approved informed consent and authorization permitting&#xD;
             the release of personal health information&#xD;
&#xD;
          -  Patients of child-bearing potential must have a negative serum pregnancy test prior to&#xD;
             study entry (within 72 hours prior to initiation of study treatment) and be practicing&#xD;
             an effective form of contraception; women should not breast-feed while on this study&#xD;
&#xD;
          -  Patients must not be receiving any other investigational agent&#xD;
&#xD;
          -  Patients should have an audiogram at baseline, and patients with pre-existing hearing&#xD;
             loss or hearing loss during treatment should be assessed frequently during cisplatin&#xD;
             therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have received previous pelvic or abdominal radiation, cytotoxic&#xD;
             chemotherapy, or previous therapy of any kind for this malignancy or any pelvic or&#xD;
             abdominal radiation for any prior malignancy&#xD;
&#xD;
          -  Patients with active infection&#xD;
&#xD;
          -  Patients who have circumstances that will not permit completion of this study or the&#xD;
             required follow-up&#xD;
&#xD;
          -  Patients with renal abnormalities, such as pelvic kidney, horseshoe kidney, or renal&#xD;
             transplantation, that would require modification of radiation fields&#xD;
&#xD;
          -  Patients with a history of other invasive malignancies, with the exception of&#xD;
             non-melanoma skin cancer, are excluded if there is any evidence of other malignancy&#xD;
             being present within the last five years; patients are also excluded if their previous&#xD;
             cancer treatment prevents full delivery of this protocol therapy&#xD;
&#xD;
          -  Patients who have undergone major surgery, excluding diagnostic biopsy, within 30 days&#xD;
             (to allow for full recovery) prior to registration&#xD;
&#xD;
          -  Patients who have a significant history of cardiac disease, i.e., uncontrolled&#xD;
             hypertension, unstable angina, congestive heart failure, or uncontrolled arrhythmias&#xD;
             within 6 months of registration&#xD;
&#xD;
          -  Patients with a history of prior treatment with ipilimumab, anti-programmed cell death&#xD;
             (PD) 1 antibody, cluster of differentiation (CD)137 agonist or other immune activating&#xD;
             therapy such as anti-CD 40 antibody&#xD;
&#xD;
          -  Patients who are receiving any other investigational agents&#xD;
&#xD;
          -  Autoimmune disease: patients with a history of inflammatory bowel disease, including&#xD;
             ulcerative colitis and Crohn's disease, are excluded from this study, as are patients&#xD;
             with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic&#xD;
             progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune&#xD;
             vasculitis [e.g., Wegener's Granulomatosis]); central nervous system (CNS) or motor&#xD;
             neuropathy considered of autoimmune origin (e.g. Guillain-Barre syndrome and&#xD;
             myasthenia gravis, multiple sclerosis)&#xD;
&#xD;
          -  Patients with known immune impairment who may be unable to respond to anti-cytotoxic&#xD;
             T-lymphocyte-associated protein 4 (CTLA 4) antibody&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition ipilimumab or other agents used in study&#xD;
&#xD;
          -  Patients with chronic human immunodeficiency virus (HIV), hepatitis B or hepatitis C&#xD;
             infections should be excluded&#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>Jyoti S Mayadev</last_name>
    <role>Principal Investigator</role>
    <affiliation>NRG Oncology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Los Angeles County-USC Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>USC / Norris Comprehensive Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC Irvine Health/Chao Family Comprehensive Cancer Center</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California Davis Comprehensive Cancer Center</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hartford Hospital</name>
      <address>
        <city>Hartford</city>
        <state>Connecticut</state>
        <zip>06102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Hospital of Central Connecticut</name>
      <address>
        <city>New Britain</city>
        <state>Connecticut</state>
        <zip>06050</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Augusta University Medical Center</name>
      <address>
        <city>Augusta</city>
        <state>Georgia</state>
        <zip>30912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of New Mexico Cancer Center</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montefiore Medical Center-Einstein Campus</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10461</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Case Western Reserve University</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Foundation</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Oklahoma Health Sciences Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson University Hospital</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fox Chase Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women and Infants Hospital</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Commonwealth University/Massey Cancer Center</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>October 18, 2012</study_first_submitted>
  <study_first_submitted_qc>October 18, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 22, 2012</study_first_posted>
  <last_update_submitted>September 1, 2020</last_update_submitted>
  <last_update_submitted_qc>September 1, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 2, 2020</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>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Uterine Cervical Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Adenosquamous</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cisplatin</mesh_term>
    <mesh_term>Ipilimumab</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01711515
org study id: NCI-2012-01733
secondary id: NCI-2012-01733
secondary id: GOG-PIS1102
secondary id: GOG-9929
secondary id: GOG-9929
secondary id: GOG-9929
secondary id: U10CA180830
secondary id: U10CA180868
secondary id: U10CA027469
nct id: NCT01711515
lead sponsor: 
collaborator: 
has dmc: No
This phase I trial studies the side effects and best dose of ipilimumab when given after
      chemoradiation therapy in treating patients with stages IB2-IIB or IIIB-IVA cervical cancer.
      Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of
      tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them
      from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink
      tumors. Monoclonal antibodies, such as ipilimumab, may find tumor cells and help carry
      tumor-killing substances to them. Giving ipilimumab together with chemoradiation therapy may
      be a better way treat cervical cancer.
PRIMARY OBJECTIVES:

      I. To estimate the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of
      adjuvant ipilimumab following concurrent weekly cisplatin and extended field radiation in
      women with newly diagnosed locally advanced cervical cancer stage IB2/ IIA with-positive
      para-aortic lymph nodes only and stage IIB/IIIB/IVA with positive lymph nodes.

      II. To determine the feasibility of the treatment regimen over the four cycles of adjuvant
      ipilimumab once the MTD is estimated.

      III. To assess the toxicities of the treatment regimen per the National Cancer Institute
      (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

      SECONDARY OBJECTIVES:

      I. To examine progression free survival for 1 year after study completion. II. To determine
      site of recurrence, loco-regional versus distant, for one year after completion of therapy.

      III. To estimate the frequency of chronic toxicities experienced within one year after
      completion of therapy.

      TERTIARY OBJECTIVES:

      I. To enumerate the human papillomavirus (HPV)-subtype-specific T-cells and characterize the
      kinetics of HPV-subtype-specific T-cell expansion associated with chemoradiation and
      ipilimumab treatment.

      II. To characterize the association between differential expression of immune markers on
      leukocytes from human leukocyte antigen (HLA)-A*0201 patients and response to chemoradiation
      and ipilimumab treatment.

      III. To assess qualitative changes in maximum standardized uptake value (SUVmax) from
      positron emission tomography (PET)/computed tomography (CT) after treatment with
      chemoradiation and ipilimumab.

      IV. To bank residual plasma (obtained from leukocyte processing) for future research.

      OUTLINE: This is a dose-escalation study of ipilimumab.

      Patients receive cisplatin intravenously (IV) over 1 hour on days 1, 8, 15, 22, 29, and 36,
      undergo external beam radiation therapy 5 days a week for 6 weeks, and then undergo
      intracavitary brachytherapy for approximately 2 weeks. Within 2 weeks, patients receive
      ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks.

      After completion of study treatment, patients are followed up every 3 months for 1 year and
      then every 6 months for 1 year.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: DLTs occurring during adjuvant ipilimumab in the dose escalation phase
time frame: During first 2 courses of treatment
measure: DLTs occurring in the feasibility phase
time frame: Over 4 courses of treatment
measure: Toxicities as assessed by CTCAE version 4
time frame: Up to 2 years post-treatment
measure: Response rate in patients enrolled with measurable disease assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
time frame: Up to 2 years post-treatment
description: Relationships of translational research endpoints to response will be explored if practical.
measure: Progression-free survival (PFS)
time frame: From time of study entry to time of progression or death, whichever occurs first, assessed up to 1 year post-treatment
description: Will be summarized using Kaplan-Meier plots. Relationships of translational research endpoints to PFS will be explored if practical.
measure: Overall survival
time frame: From time of study entry to time of death or the date the patient was last confirmed to be alive, assessed up to 1 year post-treatment
description: Will be summarized using Kaplan-Meier plots.
measure: Location of recurrence (loco-regional versus distant)
time frame: Up to 1 year post-treatment
measure: Chronic toxicities experienced within one year of completion of therapy
time frame: Up to 1 year post-treatment
measure: Enumeration of HPV-specific T-cells
time frame: Up to 2 years
description: Summary statistics (and graphs) of translational research endpoints will be done by dose level. Relationships of these endpoints to response and PFS will be explored if practical.
measure: Kinetics of HPV-specific T-cell expansion
time frame: Up to 2 years
description: Summary statistics (and graphs) of translational research endpoints will be done by dose level. Relationships of these endpoints to response and PFS will be explored if practical.
measure: Characterization of differential activated T-cell responses based on HLA-subtype A*0201
time frame: Up to 2 years
description: Summary statistics (and graphs) of translational research endpoints will be done by dose level. Relationships of these endpoints to response and PFS will be explored if practical.
measure: Measurable parameters from the fludeoxyglucose F 18 (FDG)-PET/CT, including SUVmax of the primary tumor, metabolic tumor volume (MTV) if available, the presence of abnormal FDG uptake within lymph nodes
time frame: Up to 2 years
description: Summary statistics (and graphs) of translational research endpoints will be done by dose level. Relationships of these endpoints to response and PFS will be explored if practical. Within-patient changes in the FDG-PET/CT SUVmax and MTV (if available) will be examined.
arm group label: Treatment (cisplatin, radiation therapy, and ipilimumab)
arm group type: Experimental
description: Patients receive cisplatin IV over 1 hour on days 1, 8, 15, 22, 29, and 36, undergo extended beam radiation therapy 5 days a week for 6 weeks, and then undergo intracavitary brachytherapy for approximately 2 weeks. Within 2 weeks, patients receive ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks.
intervention type: Drug
intervention name: Cisplatin
description: Given IV
arm group label: Treatment (cisplatin, radiation therapy, and ipilimumab)
other name: Abiplatin
other name: Blastolem
other name: Briplatin
other name: CDDP
other name: Cis-diammine-dichloroplatinum
other name: Cis-diamminedichloridoplatinum
other name: Cis-diamminedichloro Platinum (II)
other name: Cis-diamminedichloroplatinum
other name: Cis-dichloroammine Platinum (II)
other name: Cis-platinous Diamine Dichloride
other name: Cis-platinum
other name: Cis-platinum II
other name: Cis-platinum II Diamine Dichloride
other name: Cismaplat
other name: Cisplatina
other name: Cisplatinum
other name: Cisplatyl
other name: Citoplatino
other name: Citosin
other name: Cysplatyna
other name: DDP
other name: Lederplatin
other name: Metaplatin
other name: Neoplatin
other name: Peyrone''s Chloride
other name: Peyrone''s Salt
other name: Placis
other name: Plastistil
other name: Platamine
other name: Platiblastin
other name: Platiblastin-S
other name: Platinex
other name: Platinol
other name: Platinol- AQ
other name: Platinol-AQ
other name: Platinol-AQ VHA Plus
other name: Platinoxan
other name: Platinum
other name: Platinum Diamminodichloride
other name: Platiran
other name: Platistin
other name: Platosin
intervention type: Radiation
intervention name: External Beam Radiation Therapy
description: Undergo external beam radiation therapy
arm group label: Treatment (cisplatin, radiation therapy, and ipilimumab)
other name: Definitive Radiation Therapy
other name: EBRT
other name: External Beam Radiation
other name: External Beam Radiotherapy
other name: External Beam RT
other name: external radiation
other name: External Radiation Therapy
other name: external-beam radiation
other name: Radiation, External Beam
intervention type: Radiation
intervention name: Internal Radiation Therapy
description: Undergo intracavitary brachytherapy
arm group label: Treatment (cisplatin, radiation therapy, and ipilimumab)
other name: Brachytherapy
other name: Brachytherapy, NOS
other name: Internal Radiation
other name: Internal Radiation Brachytherapy
other name: Radiation Brachytherapy
other name: Radiation, Internal
intervention type: Biological
intervention name: Ipilimumab
description: Given IV
arm group label: Treatment (cisplatin, radiation therapy, and ipilimumab)
other name: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
other name: BMS-734016
other name: MDX-010
other name: MDX-CTLA4
other name: Yervoy
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (cisplatin, radiation therapy, and ipilimumab)
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jyoti S Mayadev
role: Principal Investigator
affiliation: NRG Oncology
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country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Uterine Cervical Neoplasms
mesh term: Carcinoma, Adenosquamous
mesh term: Cisplatin
mesh term: Ipilimumab