<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/NCT03834571</url>
  </required_header>
  <id_info>
    <org_study_id>AMC-102</org_study_id>
    <secondary_id>NCI-2018-01903</secondary_id>
    <secondary_id>AMC-102</secondary_id>
    <secondary_id>AMC-102</secondary_id>
    <secondary_id>UM1CA121947</secondary_id>
    <nct_id>NCT03834571</nct_id>
  </id_info>
  <brief_title>Testing the Addition of Paclitaxel and Carboplatin Given After Standard Chemotherapy and Radiation for Cervical Cancer in HIV-positive Women</brief_title>
  <official_title>A Randomized Phase II Trial of Concurrent Chemotherapy and Pelvic Radiation Therapy With or Without Paclitaxel and Carboplatin in HIV-positive Women With Locally Advanced Cervical Cancer (LACC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AIDS Malignancy Consortium</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Emmes Company, LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Stellenbosch</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Arkansas</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>AIDS Malignancy Consortium</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies how well standard chemotherapy and radiation therapy given with&#xD;
      or without paclitaxel and carboplatin work in treating human immunodeficiency virus&#xD;
      (HIV)-positive women with cervical cancer that has spread to nearby tissue or lymph nodes.&#xD;
      Drugs used in chemotherapy, such as cisplatin, paclitaxel, and carboplatin work in different&#xD;
      ways to stop the growth of tumor cells. They may either kill the cancer cells by stopping&#xD;
      them from dividing, or by stopping them from spreading. Radiation therapy to the pelvis&#xD;
      destroys potential cancer cells in the pelvic area and significantly reduces the risk of&#xD;
      tumor recurrence in the pelvic area. It is not yet known if giving chemotherapy and radiation&#xD;
      therapy with paclitaxel and carboplatin afterward may work better than than just chemotherapy&#xD;
      and radiation therapy in treating HIV-positive patients with advanced cervical cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      STANDARD CARE: All participants receive cisplatin intravenously (IV) over 30-60 minutes on&#xD;
      days 1, 8, 15, 22, 29, and 36. Patients also undergo radiation therapy over 2-5 fractions for&#xD;
      5 days a week, for up to 8 weeks in the absence of disease progression or unacceptable&#xD;
      toxicity. Four (4) to 8 weeks after finishing standard chemotherapy and radiation,&#xD;
      participants are randomized to 1 of 2 arms.&#xD;
&#xD;
      RANDOMIZED ARMS:&#xD;
&#xD;
      Arm I: Patients receive carboplatin IV over 1 hour and paclitaxel IV over 3 hours on day 1.&#xD;
      Courses repeat every 21 days for up to 4 courses in the absence of disease progression or&#xD;
      unacceptable toxicity. Participants are followed at 3, 6, 9, 12, 18 and 24 months for&#xD;
      recurrence or progression.&#xD;
&#xD;
      Arm II: Participants undergo active monitoring at 3, 6, 9, 12, 18 and 24 months for&#xD;
      recurrence or progression.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Not approved by CTEP&#xD;
  </why_stopped>
  <start_date type="Anticipated">May 31, 2022</start_date>
  <completion_date type="Anticipated">January 2025</completion_date>
  <primary_completion_date type="Anticipated">January 2025</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>Parallel Assignment</intervention_model>
    <intervention_model_description>All participants will receive standard chemotherapy and radiation for the first 8 weeks of the trial. Four (4) to 8 weeks after finishing standard therapy, participants meeting eligibility criteria for randomization will be assigned to 1 of 2 arms. Arm 1 will receive up to 4 cycles of adjuvant IV chemotherapy (carboplatin and paclitaxel, 21-day cycle length), and arm 2 will undergo active monitoring for cancer recurrence or progression. All participants will be monitored every 3 months for recurrence or progression through 2 years after study enrollment.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression-free survival (PFS) evaluated using Response Evaluation Criteria in Solid Tumors 1.1</measure>
    <time_frame>The time from registration enrollment to disease recurrence, disease progression, or death for any reason, assessed up to 2 years</time_frame>
    <description>The intervention arm will be compared to the control arm for improvement in PFS via one-sided log-rank test. This test will be conducted once for the interim analysis and once for the final analysis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The frequency of adverse events (AEs) and their severity will be tabulated to evaluate the safety and tolerability. Safety and tolerability will be evaluated through tracking the number of dose delays, dose reductions, missing doses, and number of doses received and compliance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival by stage</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The Kaplan Meier method will be used to estimate the 2-year PFS and corresponding 95% confidence intervals of human immunodeficiency virus (HIV)-infected women with locally advanced cervical cancer (LACC) treated on study, stratified by FIGO 2018 stage.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment effect on participants HIV disease status by assessing CD4 counts</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Descriptive statistics will be used to describe the effects of treatment on participants' HIV disease status by assessing CD4 counts.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment effect on HIV disease status by assessing HIV viral load</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Descriptive statistics will be used to describe the effects of treatment on participants' HIV disease status by assessing HIV viral load.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cervical cancer recurrence patterns</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Binomial proportions and their corresponding 95% confidence intervals will be used to describe cervical cancer recurrence patterns in HIV-infected participants with LACC defined as loco-regional and/or distant recurrences.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>From entry to protocol to death; or for living participants, the date of last contact, assessed up to 2 years</time_frame>
    <description>The Kaplan Meier method and corresponding 95% confidence interval will be used to estimate the overall survival. The causes of death will be listed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS) in women not meeting criteria for randomization by stage</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The Kaplan Meier method will be used to estimate the 2-year PFS and corresponding 95% confidence intervals of HIV-infected women with LACC treated on study but who did not meet the eligibility criteria for randomization, stratified by FIGO 2018 stage.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Evaluation of cervical human papilloma virus (HPV) types</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Counts and binomial proportions will be used to evaluate the cervical HPV types present in the HIV-positive women with cervical cancer.</description>
  </other_outcome>
  <other_outcome>
    <measure>Persistence of cervical HPV pre-treatment</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>McNemar's test will be used to assess persistence of cervical HPV pre-treatment.</description>
  </other_outcome>
  <other_outcome>
    <measure>Persistence of cervical HPV post-treatment</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>McNemar's test will be used to assess persistence of cervical HPV post-treatment.</description>
  </other_outcome>
  <other_outcome>
    <measure>Presence of HPV in the anus pre-treatment</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>McNemar's test will be used to assess the presence of HPV in the anus pre-treatment.</description>
  </other_outcome>
  <other_outcome>
    <measure>Presence of HPV in the anus post-treatment</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>McNemar's test will be used to assess the presence of HPV in the anus post-treatment.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Cervical Adenocarcinoma</condition>
  <condition>Cervical Adenosquamous Carcinoma</condition>
  <condition>Cervical Squamous Cell Carcinoma, Not Otherwise Specified</condition>
  <condition>FIGO Stage IIB Cervix Carcinoma</condition>
  <condition>FIGO Stage III Cervix Carcinoma</condition>
  <condition>FIGO Stage IVA Cervix Carcinoma</condition>
  <condition>HIV Infection</condition>
  <arm_group>
    <arm_group_label>Arm I (standard care, carboplatin, paclitaxel)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>STANDARD CARE: Patients receive cisplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Patients also undergo radiation therapy over 2-5 fractions 5 days a week for up to 8 weeks in the absence if disease progression or unacceptable toxicity. 4-8 weeks following standard of care.&#xD;
4-8 weeks following standard care, patients receive carboplatin IV over 1 hour and paclitaxel IV over 3 hours on day 1. Courses repeat every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (standard care, active monitoring)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>STANDARD CARE: Patients receive cisplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Patients also undergo radiation therapy over 2-5 fractions 5 days a week for up to 8 weeks in the absence if disease progression or unacceptable toxicity. 4-8 weeks following standard of care.&#xD;
4-8 weeks following standard care, patients undergo active monitoring at 3, 6, 9, 12, 18 and 24 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (standard care, carboplatin, paclitaxel)</arm_group_label>
    <other_name>Blastocarb</other_name>
    <other_name>Carboplat</other_name>
    <other_name>Carboplatin Hexal</other_name>
    <other_name>Carboplatino</other_name>
    <other_name>Carbosin</other_name>
    <other_name>Carbosol</other_name>
    <other_name>Carbotec</other_name>
    <other_name>CBDCA</other_name>
    <other_name>Displata</other_name>
    <other_name>Ercar</other_name>
    <other_name>JM-8</other_name>
    <other_name>Nealorin</other_name>
    <other_name>Novoplatinum</other_name>
    <other_name>Paraplatin</other_name>
    <other_name>Paraplatin AQ</other_name>
    <other_name>Paraplatine</other_name>
    <other_name>Platinwas</other_name>
    <other_name>Ribocarbo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (standard care, carboplatin, paclitaxel)</arm_group_label>
    <arm_group_label>Arm II (standard care, active monitoring)</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>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (standard care, carboplatin, paclitaxel)</arm_group_label>
    <other_name>Anzatax</other_name>
    <other_name>Asotax</other_name>
    <other_name>Bristaxol</other_name>
    <other_name>Praxel</other_name>
    <other_name>Taxol</other_name>
    <other_name>Taxol Konzentrat</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Patient Monitoring</intervention_name>
    <description>Undergo active monitoring</description>
    <arm_group_label>Arm II (standard care, active monitoring)</arm_group_label>
    <other_name>monitor</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiation Therapy</intervention_name>
    <description>Undergo radiation</description>
    <arm_group_label>Arm I (standard care, carboplatin, paclitaxel)</arm_group_label>
    <arm_group_label>Arm II (standard care, active monitoring)</arm_group_label>
    <other_name>Cancer Radiotherapy</other_name>
    <other_name>Irradiate</other_name>
    <other_name>Irradiated</other_name>
    <other_name>irradiation</other_name>
    <other_name>Radiation</other_name>
    <other_name>Radiotherapeutics</other_name>
    <other_name>RADIOTHERAPY</other_name>
    <other_name>RT</other_name>
    <other_name>Therapy, Radiation</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        This trial will be conducted at selected AIDS Malignancy Consortium sites in Sub-Saharan&#xD;
        Africa.&#xD;
&#xD;
        Eligibility Criteria for Screening&#xD;
&#xD;
          -  Ability to understand and the willingness to provide informed consent.&#xD;
&#xD;
          -  Participant has clinically diagnosed LACC and self-reports as HIV-positive&#xD;
&#xD;
          -  Age ≥ 18 years. DOB and age will be determined based on best possible information or&#xD;
             documentation available.&#xD;
&#xD;
          -  ECOG performance status ≤ 2 (Karnofsky ≥ 50%, see Appendix III).&#xD;
&#xD;
        Inclusion Criteria for chemoradiation treatment enrollment:&#xD;
&#xD;
          -  Participants with locally advanced primary, untreated, histologically-confirmed,&#xD;
             documented invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous&#xD;
             carcinoma of the uterine cervix, adequately clinically staged by standard clinical&#xD;
             guidelines, with Federation of Gynecology and Obstetrics (FIGO) stages IIB, III, or&#xD;
             IVA&#xD;
&#xD;
          -  HIV positive. Documentation of HIV-1 infection by means of any one of the following:&#xD;
&#xD;
               -  Documentation of receipt of ART by a licensed health care provider (documentation&#xD;
                  may be a record of an ART prescription in the participant's medical record, a&#xD;
                  written prescription in the name of the participant for ART, or pill bottles for&#xD;
                  ART with a label showing the participant's name)&#xD;
&#xD;
               -  HIV-1 ribonucleic acid (RNA) detection by a licensed HIV-1 RNA assay&#xD;
                  demonstrating &gt;1000 RNA copies/mL confirmed by a licensed screening antibody&#xD;
                  and/or HIV antibody antigen combination assay&#xD;
&#xD;
               -  Any licensed HIV screening antibody and/or HIV antibody/antigen combination assay&#xD;
                  confirmed by a second licensed HIV assay such as a HIV-1 Western blot&#xD;
                  confirmation or HIV rapid multispot antibody differentiation assay.&#xD;
&#xD;
                    -  Note: The term &quot;licensed&quot; refers to a kit that has been certified or&#xD;
                       licensed by an oversight body within the participating country and validated&#xD;
                       internally. WHO (World Health Organization) and CDC (Centers for Disease&#xD;
                       Control and Prevention) guidelines mandate that confirmation of the initial&#xD;
                       test result must use a test that is different from the one used for the&#xD;
                       initial assessment. A reactive initial rapid test should be confirmed by&#xD;
                       either another type of rapid assay or an E/CIA that is based on a different&#xD;
                       antigen preparation and/or different test principle (e.g., indirect versus&#xD;
                       competitive), or a Western blot or a plasma HIV-1 RNA viral load.&#xD;
&#xD;
          -  Hemoglobin &gt;= 10 g/dL (6.2 mmol/L) (participants receiving transfusion are permitted)&#xD;
             (within 4 weeks prior to enrollment)&#xD;
&#xD;
          -  Leukocytes: &gt;= 3,000/mm^3 (3.0 x 10^9/L) (within 4 weeks prior to enrollment)&#xD;
&#xD;
          -  Absolute neutrophil count: &gt;= 1,500/mm^3 (1.5 x 10^9/L) (within 4 weeks prior to&#xD;
             enrollment)&#xD;
&#xD;
          -  Platelets: &gt;= 100,000/mm^3 (100 x 10^9/L) (within 4 weeks prior to enrollment)&#xD;
&#xD;
          -  CD4 T-cell count a minimum of 200 cells/uL (within 4 weeks prior to enrollment)&#xD;
&#xD;
          -  Total bilirubin =&lt; 2 x institutional upper limit of normal (ULN) unless related to&#xD;
             antiretroviral use (e.g., atazanavir or indinavir), then the direct bilirubin must be&#xD;
             =&lt; 2 x ULN (within 4 weeks prior to enrollment)&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase&#xD;
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]):&#xD;
             =&lt; 3 x ULN (within 4 weeks prior to enrollment)&#xD;
&#xD;
          -  Creatinine levels within normal institutional limits or, creatinine clearance &gt;= 60&#xD;
             mL/min/1.73 m^2 (1.00 mL/s) calculated by the Cockcroft-Gault equation for women for&#xD;
             participants with creatinine levels above institutional normal (within 4 weeks prior&#xD;
             to enrollment)&#xD;
&#xD;
          -  All participants must be prescribed combination antiretroviral therapy with the goal&#xD;
             of virological suppression using an acceptable regimen that adheres to national&#xD;
             guidelines for treatment of HIV infection. If on a ritonavir- or cobicistat-based&#xD;
             regimen, the participant must be switched to a non-ritonavir/ cobicistat-based regimen&#xD;
             at least 7 days before treatment enrollment. Participants not on ART must start an&#xD;
             acceptable regimen at least 7 days before treatment enrollment.&#xD;
&#xD;
          -  In the investigator's opinion the participant is suitable for treatment with radical&#xD;
             intent using concurrent chemotherapy and pelvic radiation followed by adjuvant&#xD;
             chemotherapy&#xD;
&#xD;
          -  Participants of childbearing potential, defined as a sexually mature woman who: 1) has&#xD;
             not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally&#xD;
             postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in&#xD;
             the preceding 24 consecutive months), must have a negative urine or serum pregnancy&#xD;
             test within 3 weeks prior to enrollment and agree to use an effective form of&#xD;
             contraception (e.g., barrier contraception, highly effective hormonal contraception)&#xD;
             for the duration of treatment and for 6 weeks after stopping treatment&#xD;
&#xD;
          -  Life expectancy of greater than 6 months&#xD;
&#xD;
        Exclusion Criteria for chemoradiation treatment enrollment:&#xD;
&#xD;
          -  Participants who have had chemotherapy for cervical cancer within 4 weeks (6 weeks for&#xD;
             nitrosoureas or mitomycin C) prior to entering the study&#xD;
&#xD;
          -  Participants who are receiving any other investigational agents&#xD;
&#xD;
          -  Participants who have not recovered from adverse events due to prior anti-cancer&#xD;
             therapy (i.e., have residual toxicity &gt; grade 1).&#xD;
&#xD;
          -  Participants who have undergone hysterectomy including supracervical hysterectomy&#xD;
&#xD;
          -  Acute active (such as tuberculosis or malaria), serious, uncontrolled infection&#xD;
&#xD;
          -  Prior invasive malignancy requiring systemic chemotherapy diagnosed within the past 24&#xD;
             months (other than LACC)&#xD;
&#xD;
          -  A medical or psychiatric illness that precludes ability to give informed consent or is&#xD;
             likely to interfere with the ability to comply with the protocol stipulations&#xD;
&#xD;
          -  Participants with circumstances that will not permit completion of the study or&#xD;
             required follow-up. For instance, if travel to and from treatment site is an issue&#xD;
&#xD;
          -  Participants with carcinoma of the cervical stump&#xD;
&#xD;
          -  Participants with history of cardiovascular disease manifested as:&#xD;
&#xD;
               -  History of myocardial infarction&#xD;
&#xD;
               -  Unstable angina&#xD;
&#xD;
               -  Currently taking medication for treatment of angina&#xD;
&#xD;
               -  History of coronary artery bypass surgery&#xD;
&#xD;
               -  New York Heart Association class 3 or 4 heart failure&#xD;
&#xD;
          -  Participants with enlarged para-aortic lymph node involvement above L3 on imaging that&#xD;
             are suspicious for metastasis&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or&#xD;
             biological composition to study drugs (cisplatin, carboplatin, and paclitaxel)&#xD;
&#xD;
          -  Participants who are breastfeeding a child. Cisplatin is known to be excreted in human&#xD;
             milk.&#xD;
&#xD;
        Eligibility for Randomization&#xD;
&#xD;
          -  Participants must have organ and marrow function within the following parameters&#xD;
             within 4-8 weeks post CDDP/RT to be eligible for randomization&#xD;
&#xD;
          -  Absolute neutrophil count: ≥1,500/mm3 (1.5 x 109/L)&#xD;
&#xD;
          -  Platelets: ≥ 100,000/mm3 (100 x 109/L)&#xD;
&#xD;
          -  CD4 T-cell &gt; 100 cells/µL&#xD;
&#xD;
          -  HIV viral load &lt; 400 copies/mL&#xD;
&#xD;
          -  ECOG performance status ≤ 2 (Karnofsky ≥ 50%).&#xD;
&#xD;
          -  Successful completion of CDDP/RT, defined as receiving 4-6 cycles of cisplatin and&#xD;
             completion of the equivalent dose per fraction of &gt;78 Gy to Point A.&#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>Ntokozo Ndlovu</last_name>
    <role>Principal Investigator</role>
    <affiliation>Parirenyatwa Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stellenbosch University</name>
      <address>
        <city>Cape Town</city>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Witwatersrand</name>
      <address>
        <city>Johannesburg</city>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parirenyatwa Hospital</name>
      <address>
        <city>Harare</city>
        <country>Zimbabwe</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>South Africa</country>
    <country>Zimbabwe</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>February 6, 2019</study_first_submitted>
  <study_first_submitted_qc>February 6, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 8, 2019</study_first_posted>
  <last_update_submitted>June 14, 2022</last_update_submitted>
  <last_update_submitted_qc>June 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cervical Cancer</keyword>
  <keyword>HIV Infection</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>HIV Infections</mesh_term>
    <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>Paclitaxel</mesh_term>
    <mesh_term>Cisplatin</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Albumin-Bound Paclitaxel</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/NCT03834571
org study id: AMC-102
secondary id: NCI-2018-01903
secondary id: AMC-102
secondary id: AMC-102
secondary id: UM1CA121947
nct id: NCT03834571
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This phase II trial studies how well standard chemotherapy and radiation therapy given with
      or without paclitaxel and carboplatin work in treating human immunodeficiency virus
      (HIV)-positive women with cervical cancer that has spread to nearby tissue or lymph nodes.
      Drugs used in chemotherapy, such as cisplatin, paclitaxel, and carboplatin work in different
      ways to stop the growth of tumor cells. They may either kill the cancer cells by stopping
      them from dividing, or by stopping them from spreading. Radiation therapy to the pelvis
      destroys potential cancer cells in the pelvic area and significantly reduces the risk of
      tumor recurrence in the pelvic area. It is not yet known if giving chemotherapy and radiation
      therapy with paclitaxel and carboplatin afterward may work better than than just chemotherapy
      and radiation therapy in treating HIV-positive patients with advanced cervical cancer.
STANDARD CARE: All participants receive cisplatin intravenously (IV) over 30-60 minutes on
      days 1, 8, 15, 22, 29, and 36. Patients also undergo radiation therapy over 2-5 fractions for
      5 days a week, for up to 8 weeks in the absence of disease progression or unacceptable
      toxicity. Four (4) to 8 weeks after finishing standard chemotherapy and radiation,
      participants are randomized to 1 of 2 arms.

      RANDOMIZED ARMS:

      Arm I: Patients receive carboplatin IV over 1 hour and paclitaxel IV over 3 hours on day 1.
      Courses repeat every 21 days for up to 4 courses in the absence of disease progression or
      unacceptable toxicity. Participants are followed at 3, 6, 9, 12, 18 and 24 months for
      recurrence or progression.

      Arm II: Participants undergo active monitoring at 3, 6, 9, 12, 18 and 24 months for
      recurrence or progression.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: All participants will receive standard chemotherapy and radiation for the first 8 weeks of the trial. Four (4) to 8 weeks after finishing standard therapy, participants meeting eligibility criteria for randomization will be assigned to 1 of 2 arms. Arm 1 will receive up to 4 cycles of adjuvant IV chemotherapy (carboplatin and paclitaxel, 21-day cycle length), and arm 2 will undergo active monitoring for cancer recurrence or progression. All participants will be monitored every 3 months for recurrence or progression through 2 years after study enrollment.
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free survival (PFS) evaluated using Response Evaluation Criteria in Solid Tumors 1.1
time frame: The time from registration enrollment to disease recurrence, disease progression, or death for any reason, assessed up to 2 years
description: The intervention arm will be compared to the control arm for improvement in PFS via one-sided log-rank test. This test will be conducted once for the interim analysis and once for the final analysis.
measure: Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
time frame: Up to 2 years
description: The frequency of adverse events (AEs) and their severity will be tabulated to evaluate the safety and tolerability. Safety and tolerability will be evaluated through tracking the number of dose delays, dose reductions, missing doses, and number of doses received and compliance.
measure: Progression free survival by stage
time frame: Up to 2 years
description: The Kaplan Meier method will be used to estimate the 2-year PFS and corresponding 95% confidence intervals of human immunodeficiency virus (HIV)-infected women with locally advanced cervical cancer (LACC) treated on study, stratified by FIGO 2018 stage.
measure: Treatment effect on participants HIV disease status by assessing CD4 counts
time frame: Up to 2 years
description: Descriptive statistics will be used to describe the effects of treatment on participants' HIV disease status by assessing CD4 counts.
measure: Treatment effect on HIV disease status by assessing HIV viral load
time frame: Up to 2 years
description: Descriptive statistics will be used to describe the effects of treatment on participants' HIV disease status by assessing HIV viral load.
measure: Cervical cancer recurrence patterns
time frame: Up to 2 years
description: Binomial proportions and their corresponding 95% confidence intervals will be used to describe cervical cancer recurrence patterns in HIV-infected participants with LACC defined as loco-regional and/or distant recurrences.
measure: Overall survival (OS)
time frame: From entry to protocol to death; or for living participants, the date of last contact, assessed up to 2 years
description: The Kaplan Meier method and corresponding 95% confidence interval will be used to estimate the overall survival. The causes of death will be listed.
measure: Progression free survival (PFS) in women not meeting criteria for randomization by stage
time frame: Up to 2 years
description: The Kaplan Meier method will be used to estimate the 2-year PFS and corresponding 95% confidence intervals of HIV-infected women with LACC treated on study but who did not meet the eligibility criteria for randomization, stratified by FIGO 2018 stage.
measure: Evaluation of cervical human papilloma virus (HPV) types
time frame: Up to 2 years
description: Counts and binomial proportions will be used to evaluate the cervical HPV types present in the HIV-positive women with cervical cancer.
measure: Persistence of cervical HPV pre-treatment
time frame: Up to 2 years
description: McNemar's test will be used to assess persistence of cervical HPV pre-treatment.
measure: Persistence of cervical HPV post-treatment
time frame: Up to 2 years
description: McNemar's test will be used to assess persistence of cervical HPV post-treatment.
measure: Presence of HPV in the anus pre-treatment
time frame: Up to 2 years
description: McNemar's test will be used to assess the presence of HPV in the anus pre-treatment.
measure: Presence of HPV in the anus post-treatment
time frame: Up to 2 years
description: McNemar's test will be used to assess the presence of HPV in the anus post-treatment.
arm group label: Arm I (standard care, carboplatin, paclitaxel)
arm group type: Experimental
description: STANDARD CARE: Patients receive cisplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Patients also undergo radiation therapy over 2-5 fractions 5 days a week for up to 8 weeks in the absence if disease progression or unacceptable toxicity. 4-8 weeks following standard of care.
4-8 weeks following standard care, patients receive carboplatin IV over 1 hour and paclitaxel IV over 3 hours on day 1. Courses repeat every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
arm group label: Arm II (standard care, active monitoring)
arm group type: Active Comparator
description: STANDARD CARE: Patients receive cisplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Patients also undergo radiation therapy over 2-5 fractions 5 days a week for up to 8 weeks in the absence if disease progression or unacceptable toxicity. 4-8 weeks following standard of care.
4-8 weeks following standard care, patients undergo active monitoring at 3, 6, 9, 12, 18 and 24 months.
intervention type: Drug
intervention name: Carboplatin
description: Given IV
arm group label: Arm I (standard care, carboplatin, paclitaxel)
other name: Blastocarb
other name: Carboplat
other name: Carboplatin Hexal
other name: Carboplatino
other name: Carbosin
other name: Carbosol
other name: Carbotec
other name: CBDCA
other name: Displata
other name: Ercar
other name: JM-8
other name: Nealorin
other name: Novoplatinum
other name: Paraplatin
other name: Paraplatin AQ
other name: Paraplatine
other name: Platinwas
other name: Ribocarbo
intervention type: Drug
intervention name: Cisplatin
description: Given IV
arm group label: Arm I (standard care, carboplatin, paclitaxel)
arm group label: Arm II (standard care, active monitoring)
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: Drug
intervention name: Paclitaxel
description: Given IV
arm group label: Arm I (standard care, carboplatin, paclitaxel)
other name: Anzatax
other name: Asotax
other name: Bristaxol
other name: Praxel
other name: Taxol
other name: Taxol Konzentrat
intervention type: Procedure
intervention name: Patient Monitoring
description: Undergo active monitoring
arm group label: Arm II (standard care, active monitoring)
other name: monitor
intervention type: Radiation
intervention name: Radiation Therapy
description: Undergo radiation
arm group label: Arm I (standard care, carboplatin, paclitaxel)
arm group label: Arm II (standard care, active monitoring)
other name: Cancer Radiotherapy
other name: Irradiate
other name: Irradiated
other name: irradiation
other name: Radiation
other name: Radiotherapeutics
other name: RADIOTHERAPY
other name: RT
other name: Therapy, Radiation
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ntokozo Ndlovu
role: Principal Investigator
affiliation: Parirenyatwa Hospital
facility: 
facility: 
facility: 
country: South Africa
country: Zimbabwe
responsible party type: Sponsor
mesh term: HIV Infections
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Uterine Cervical Neoplasms
mesh term: Carcinoma, Adenosquamous
mesh term: Paclitaxel
mesh term: Cisplatin
mesh term: Carboplatin
mesh term: Albumin-Bound Paclitaxel
sharing ipd: No