<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/NCT03750539</url>
  </required_header>
  <id_info>
    <org_study_id>017/020/ICI</org_study_id>
    <nct_id>NCT03750539</nct_id>
  </id_info>
  <brief_title>Chemotherapy and Pelvic Hypofractionated Radiation Followed by Surgery Cervical Cancer</brief_title>
  <official_title>Phase II Randomized Study of Concurrent Chemotherapy and Pelvic Radiation Therapy With Standard Fractionated Compared to Hypofractionated Followed by Surgery for Patients With Locally Advanced Cervical Cancer.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Cancerología</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institute of Cancerología</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to evaluate the role of hypofractionated in the treatment of&#xD;
      locally advanced cervical cancer. The study will be conducted in Honduras and Mexico, and&#xD;
      patients will be randomized to a standard fraction (45 Gy in 25 fractions) or&#xD;
      hypofractionated (37.5Gy in 15 fractions) followed by surgery. Patients will receive weekly&#xD;
      cisplatin with their treatments at 40 mg/m2. Response rate, survival, and toxicity will be&#xD;
      evaluated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Toxicity will be assessed six times during this study. In addition to the primary endpoint of&#xD;
      patient-reported gastrointestinal toxicity, a broad range of other toxicities will be&#xD;
      comprehensively evaluated, including urinary, hematologic and dermatologic, this data will&#xD;
      allow to determining the effect of hypofractionated radiation therapy on each of these&#xD;
      aspects of toxicity from pelvic radiation. Additionally, will be recognized that it is&#xD;
      possible to advance in the understanding of the clinical risk and benefits of&#xD;
      hypofractionation.&#xD;
&#xD;
      The primary endpoint will be acute gastrointestinal toxicity using the Radiation Therapy&#xD;
      Oncology Group (RTOG) common toxicity criteria.&#xD;
&#xD;
      In total, evaluating toxicity in different time points will allow determining if&#xD;
      hypofractionation is secure concerning acute and late toxicity, that would enable to offer an&#xD;
      optional treatment to this kind of patient. Chronic gastrointestinal toxicity from radiation&#xD;
      continues to increase rapidly over two years, and then the rate of developing new toxicities&#xD;
      slows. As a result, the majority of chronic radiation-induced gastrointestinal toxicity by&#xD;
      evaluating toxicity two years after completion of radiotherapy is going to be identified.&#xD;
&#xD;
      Quality of life (QOL) will be evaluated using EORTC QLQ-CX24 and EORTC QLQ-C30, both of which&#xD;
      have been validated and available in Mexican Spanish.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 10, 2017</start_date>
  <completion_date type="Anticipated">November 10, 2021</completion_date>
  <primary_completion_date type="Anticipated">November 10, 2021</primary_completion_date>
  <phase>N/A</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>Phase II Comparative Randomized Open-label</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Acute and late toxicity.</measure>
    <time_frame>2 years</time_frame>
    <description>Number of Participants With Treatment-Related Adverse Events as Assessed by RTOG</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>2 years</time_frame>
    <description>Number of Participants dead at two years according to kaplan-meyer analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>disease specific survival</measure>
    <time_frame>2 years</time_frame>
    <description>Number of Participants dead of disease at two years according to kaplan-meyer analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>equivalent treatment</measure>
    <time_frame>2 years</time_frame>
    <description>hypofractionated radiotherapy is similar in toxicity and disease control compared to standard external beam treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Surgical complications</measure>
    <time_frame>1 year</time_frame>
    <description>comparison of surgical complications between the two arms of treatment according to The Clavien-Dindo classification.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Cervix Cancer</condition>
  <arm_group>
    <arm_group_label>Standard Treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>External Beam pelvic radiation therapy daily dose of 1.8-2 Gray (Gy) per session for 25 sessions to accomplish 45 Gy Chemotherapy ( cisplatin 40mg/m2), intravenous administration of chemotherapy once a week in an hour infusion Type II or type III open radical hysterectomy after 4-6 weeks after completion of external beam radiation</description>
  </arm_group>
  <arm_group>
    <arm_group_label>hypofractionated treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>External Beam pelvic radiation therapy daily dose of 1.8-2gy per session for 15 sessions to accomplish 37.5 Gy Chemotherapy ( cisplatin 40mg/m2), intravenous administration of chemotherapy once a week in an hour infusion Type II or type III open radical hysterectomy after 4-6 weeks after completion of external beam radiation</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Standard radiotherapy</intervention_name>
    <description>External Bean Pelvic Radiation: 50 Gy in 15 fractions, with weekly cisplatin.</description>
    <arm_group_label>Standard Treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>hypofractionated radiotherapy</intervention_name>
    <description>External Bean Pelvic Radiation: 37.5 Gy in 15 fractions, with weekly cisplatin.</description>
    <arm_group_label>hypofractionated treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Radical hysterectomy</intervention_name>
    <description>Radical hysterectomy and pelvic and paraaortic lymph node resection</description>
    <arm_group_label>Standard Treatment</arm_group_label>
    <arm_group_label>hypofractionated treatment</arm_group_label>
    <other_name>Surgery</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have International Federation of Gynecology and Obstetrics (FIGO) stage&#xD;
             IB2-IIB squamous, adenosquamous or adenocarcinoma of cervical with no disease outside&#xD;
             of the pelvis by via ultrasound.&#xD;
&#xD;
          -  No distant metastasis via chest X-ray.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2&#xD;
&#xD;
          -  Age 18&#xD;
&#xD;
          -  complete blood count (CBC)/differential obtained 14 days before study entry with&#xD;
             adequate bone marrow function defined as follows:&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) ≥ 1,500 cells/mim3&#xD;
&#xD;
          -  Platelets 100,000 cells/mim3&#xD;
&#xD;
          -  Hemoglobin 8.0 g/dl&#xD;
&#xD;
          -  White blood count 4000 cell/m3&#xD;
&#xD;
          -  An adequate renal function defined as follows:&#xD;
&#xD;
          -  Serum creatinine 1.5 mg/dl within 14 days before study entry&#xD;
&#xD;
          -  Patients with known HIV positive must have a cluster of differentiation 4 (CD4) T&#xD;
             lymphocytes count be 350 cells/mm3 within 14 days prior to study entry (note, however,&#xD;
             that HIV testing is not required for entry into this protocol). Excluding HIV positive&#xD;
             patients with invasive cervical cancer and low CD4 cell counts is necessary because&#xD;
             the treatments involved in this protocol may be significantly immunosuppressive.&#xD;
&#xD;
          -  Chest x-ray and ultrasound must be performed within 12 (8 or 12) weeks before the&#xD;
             study enrollment (I took out the ct scan of abdomen and pelvis)&#xD;
&#xD;
          -  Patient must provide study-specific informed consent before study entry.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free&#xD;
             for a minimum of 3 years (For example, carcinoma in situ of the breast or oral cavity.&#xD;
&#xD;
          -  Patients cannot have any neuroendocrine histology in pathology.&#xD;
&#xD;
          -  Prior systemic chemotherapy for the current cervical cancer, note that prior&#xD;
             chemotherapy for a different cancer is allowable.&#xD;
&#xD;
          -  Prior radiation therapy to the pelvis that would result in overlap of radiation&#xD;
             therapy fields.&#xD;
&#xD;
          -  Severe active co-morbidity, defined as follows:&#xD;
&#xD;
          -  Unstable angina or congestive heart failure requiring hospitalization within the last&#xD;
             six months.&#xD;
&#xD;
          -  Transmural myocardial infarction within the previous six months.&#xD;
&#xD;
          -  Acute bacterial or fungal infection requiring intravenous antibiotics at the time of&#xD;
             the study entry.&#xD;
&#xD;
          -  Chronic obstructive pulmonary disease exacerbation or other respiratory illness&#xD;
             requiring hospitalization or precluding study therapy at the time of study entry.&#xD;
&#xD;
          -  Coagulation defects; note, however, that coagulation parameter are not required for&#xD;
             entry into this protocol.&#xD;
&#xD;
          -  Prior allergic reaction to cisplatin or other platinum drugs.&#xD;
&#xD;
          -  Patients with para-aortic nodes or distant metastasis.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David F Cantu-de Leon, MD, Msc, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Instituto Nacional de Cancerologia, Columbia</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>David F Cantu-de Leon, MD, MSC, PhD</last_name>
    <phone>+5215537093156</phone>
    <email>dfcantu@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Lennt N Gallardo-Alvarado, MD, Msc</last_name>
    <phone>+521553702118</phone>
    <email>dra.ngallardo@yahoo.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>David Cantu de Leon</name>
      <address>
        <city>Mexico City</city>
        <state>Tlalpan</state>
        <zip>14080</zip>
        <country>Mexico</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Instituto Nacional de Cancerologia</name>
      <address>
        <city>Mexico City</city>
        <zip>14080</zip>
        <country>Mexico</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>David F Cantu de Leon, MD, PhD</last_name>
      <phone>525556280400</phone>
      <phone_ext>21016</phone_ext>
      <email>dfcantu@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Lenny N Gallardo-Alvarado, MD, MSc</last_name>
      <phone>525556280400</phone>
      <phone_ext>37000</phone_ext>
      <email>dra.ngallardo@yahoo.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Mexico</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>November 5, 2018</study_first_submitted>
  <study_first_submitted_qc>November 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 23, 2018</study_first_posted>
  <last_update_submitted>March 18, 2021</last_update_submitted>
  <last_update_submitted_qc>March 18, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 22, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Institute of Cancerología</investigator_affiliation>
    <investigator_full_name>David Cantu</investigator_full_name>
    <investigator_title>Chief of clinical trial departament</investigator_title>
  </responsible_party>
  <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>Yes</sharing_ipd>
    <ipd_description>all IPD that underlie results in a publication</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>2 years</ipd_time_frame>
    <ipd_access_criteria>the data will be shared with scientific and academic institutions or research groups that study the same topic and with the regulatory and ethical authorities that require it, to ensure the quality and accuracy of the data.</ipd_access_criteria>
  </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/NCT03750539
org study id: 017/020/ICI
nct id: NCT03750539
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of the study is to evaluate the role of hypofractionated in the treatment of
      locally advanced cervical cancer. The study will be conducted in Honduras and Mexico, and
      patients will be randomized to a standard fraction (45 Gy in 25 fractions) or
      hypofractionated (37.5Gy in 15 fractions) followed by surgery. Patients will receive weekly
      cisplatin with their treatments at 40 mg/m2. Response rate, survival, and toxicity will be
      evaluated.
Toxicity will be assessed six times during this study. In addition to the primary endpoint of
      patient-reported gastrointestinal toxicity, a broad range of other toxicities will be
      comprehensively evaluated, including urinary, hematologic and dermatologic, this data will
      allow to determining the effect of hypofractionated radiation therapy on each of these
      aspects of toxicity from pelvic radiation. Additionally, will be recognized that it is
      possible to advance in the understanding of the clinical risk and benefits of
      hypofractionation.

      The primary endpoint will be acute gastrointestinal toxicity using the Radiation Therapy
      Oncology Group (RTOG) common toxicity criteria.

      In total, evaluating toxicity in different time points will allow determining if
      hypofractionation is secure concerning acute and late toxicity, that would enable to offer an
      optional treatment to this kind of patient. Chronic gastrointestinal toxicity from radiation
      continues to increase rapidly over two years, and then the rate of developing new toxicities
      slows. As a result, the majority of chronic radiation-induced gastrointestinal toxicity by
      evaluating toxicity two years after completion of radiotherapy is going to be identified.

      Quality of life (QOL) will be evaluated using EORTC QLQ-CX24 and EORTC QLQ-C30, both of which
      have been validated and available in Mexican Spanish.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Phase II Comparative Randomized Open-label
primary purpose: Treatment
masking: None (Open Label)
measure: Acute and late toxicity.
time frame: 2 years
description: Number of Participants With Treatment-Related Adverse Events as Assessed by RTOG
measure: Overall survival
time frame: 2 years
description: Number of Participants dead at two years according to kaplan-meyer analysis
measure: disease specific survival
time frame: 2 years
description: Number of Participants dead of disease at two years according to kaplan-meyer analysis
measure: equivalent treatment
time frame: 2 years
description: hypofractionated radiotherapy is similar in toxicity and disease control compared to standard external beam treatment.
measure: Surgical complications
time frame: 1 year
description: comparison of surgical complications between the two arms of treatment according to The Clavien-Dindo classification.
arm group label: Standard Treatment
arm group type: Active Comparator
description: External Beam pelvic radiation therapy daily dose of 1.8-2 Gray (Gy) per session for 25 sessions to accomplish 45 Gy Chemotherapy ( cisplatin 40mg/m2), intravenous administration of chemotherapy once a week in an hour infusion Type II or type III open radical hysterectomy after 4-6 weeks after completion of external beam radiation
arm group label: hypofractionated treatment
arm group type: Experimental
description: External Beam pelvic radiation therapy daily dose of 1.8-2gy per session for 15 sessions to accomplish 37.5 Gy Chemotherapy ( cisplatin 40mg/m2), intravenous administration of chemotherapy once a week in an hour infusion Type II or type III open radical hysterectomy after 4-6 weeks after completion of external beam radiation
intervention type: Radiation
intervention name: Standard radiotherapy
description: External Bean Pelvic Radiation: 50 Gy in 15 fractions, with weekly cisplatin.
arm group label: Standard Treatment
intervention type: Radiation
intervention name: hypofractionated radiotherapy
description: External Bean Pelvic Radiation: 37.5 Gy in 15 fractions, with weekly cisplatin.
arm group label: hypofractionated treatment
intervention type: Procedure
intervention name: Radical hysterectomy
description: Radical hysterectomy and pelvic and paraaortic lymph node resection
arm group label: Standard Treatment
arm group label: hypofractionated treatment
other name: Surgery
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: David F Cantu-de Leon, MD, Msc, PhD
role: Principal Investigator
affiliation: Instituto Nacional de Cancerologia, Columbia
last name: David F Cantu-de Leon, MD, MSC, PhD
phone: +5215537093156
email: dfcantu@gmail.com
last name: Lennt N Gallardo-Alvarado, MD, Msc
phone: +521553702118
email: dra.ngallardo@yahoo.com
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
contact: 
contact backup: 
country: Mexico
responsible party type: Principal Investigator
investigator affiliation: National Institute of Cancerología
investigator full name: David Cantu
investigator title: Chief of clinical trial departament
mesh term: Uterine Cervical Neoplasms
sharing ipd: Yes
ipd description: all IPD that underlie results in a publication
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: 2 years
ipd access criteria: the data will be shared with scientific and academic institutions or research groups that study the same topic and with the regulatory and ethical authorities that require it, to ensure the quality and accuracy of the data.