<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/NCT04458402</url>
  </required_header>
  <id_info>
    <org_study_id>UCCC-GYN-20-01</org_study_id>
    <nct_id>NCT04458402</nct_id>
  </id_info>
  <brief_title>Adjuvant Hypofractionated Whole Pelvis Radiation Therapy in Endometrial Cancer</brief_title>
  <official_title>Phase I Study of Adjuvant Hypofractionated Whole Pelvis Radiation Therapy in Endometrial Cancer.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Teresa Meier</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Cincinnati</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Studying adjuvant hypofractionated whole pelvis radiation therapy in Endometrial Cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase I study evaluating the safety of adjuvant hypofractionated whole pelvis&#xD;
      radiation therapy (WPRT) in endometrial cancer. The primary objective of the study is to&#xD;
      determine the maximum tolerated dose per fraction (MTDF), defined by acceptable acute&#xD;
      clinician-reported GI and GU toxicity and patient-reported GI toxicity, of WPRT from among&#xD;
      the two study dose levels. Acute GI and GU toxicity will be assessed according to both the&#xD;
      NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0, and Patient Reported&#xD;
      Outcome-CTCAE (PRO-CTCAE). Clinician-reported dose-limiting toxicity (C-DLT) is a binary&#xD;
      outcome (yes/no), defined as an acute grade 3 or higher GI or GU per CTCAE, occurring within&#xD;
      three months of completing WPRT. Patient-reported DLT (P-DLT) is a binary outcome, defined by&#xD;
      a GI toxicity with a score of ≥4 on the 5-point scale per PRO-CTCAE, occurring within three&#xD;
      months of completing WPRT. The MTDF is defined as the minimum of the dose with a C-DLT rate&#xD;
      closest to the clinician-reported target C-DLT rate of 20% and the dose with a P-DLT rate&#xD;
      closest to the patient-reported target P-DLT rate of 55%. Toxicity results of NRG-RTOG 1203-&#xD;
      A Randomized Phase III Study of Standard vs. IMRT Pelvic Radiation for Post-Operative&#xD;
      Treatment of Endometrial and Cervical Cancer- were used to define the acceptable percentage&#xD;
      of DLTs. The study will accrue participants in cohorts of size 3. The starting dose level&#xD;
      will be dose level 1 (41.25 Gy in 15 fx).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 4, 2021</start_date>
  <completion_date type="Anticipated">July 4, 2025</completion_date>
  <primary_completion_date type="Anticipated">February 4, 2024</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Dose allocation will be based upon a Bayesian continual reassessment method that incorporates patient-reported outcomes (PRO-CRM17), which uses separate models for the probability of C-DLT and the probability of P-DLT, as well as the accumulated C-DLT and P-DLT data at each dose level, to sequentially allocate each new patient cohort.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety profile of hypofractionated, isoeffective whole pelvis radiation regimens for post-operative treatment of endometrial cancer using CTCAE version 5.0 and Patient Reported Outcome-CTCAE.</measure>
    <time_frame>3 months</time_frame>
    <description>Toxicity profile will be determined by assessment of acute gastrointestinal and genitourinary toxicity during WPRT and 3 months post-radiation using CTCAE version 5.0 and Patient Reported Outcome-CTCAE (PRO-CTCAE). Dose-limiting toxicity (DLT) will be defined as any acute ≥ grade 3 gastrointestinal or genitourinary per CTCAE or a score of ≥4 on the 5-point scale per PRO-CTCAE.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum tolerated dose per fraction (MTDF) of hypofractionated, isoeffective whole pelvis radiation regimens for post-operative treatment of endometrial cancer through CTCAE data and gastrointestinal PRO-CTCAE data.</measure>
    <time_frame>3 months</time_frame>
    <description>Determination of the MTDF will rely on toxicity data, specifically combined gastrointestinal and genitourinary CTCAE data and gastrointestinal PRO-CTCAE data. MTDF should not exceed &gt;20% of patients having a DLT per CTCAE or &gt;55% of patients having a dose-limiting GI toxicity per PRO-CTCAE. Further details in study design.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Impact of hypofractionated WPRT on patient quality of life using the Functional Assessment of Cancer Therapy-Endometrial version 4.0.</measure>
    <time_frame>3 months</time_frame>
    <description>Quality of life data will be obtained for exploratory analysis only.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient compliance with hypofractionated WPRT, as defined by how many patients are able to complete WPRT without a break in treatment.</measure>
    <time_frame>3 months</time_frame>
    <description>Patient compliance with radiotherapy will be recorded and used for exploratory analysis only.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">15</enrollment>
  <condition>Endometrial Cancer</condition>
  <arm_group>
    <arm_group_label>Hypofractionated Whole-Pelvis Radiotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Hypofractionated WPRT Cohort 1: 41.25 Gy in 15 fx Cohort 2: 38 Gy in 10 fx</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Hypofractionated WPRT</intervention_name>
    <description>Cohort 1: 41.25 Gy in 15 fx Cohort 1: 38 Gy in 10 fx</description>
    <arm_group_label>Hypofractionated Whole-Pelvis Radiotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with histologically confirmed stage I, II, or III endometrial cancer who&#xD;
             require pelvic radiation as determined by their treating radiation oncologist and/or&#xD;
             gynecologic oncologist. Patients may also be identified through the Gynecologic&#xD;
             Oncology Multidisciplinary Tumor Board. The decision to include Stage I patients will&#xD;
             be based on risk factors for recurrence including tumor grade, extent of myometrial&#xD;
             invasion, presence of lymphovascular space invasion, and histology (endometrioid,&#xD;
             papillary serous, clear cell, carcinosarcoma). Stage I patients may include those who&#xD;
             are ineligible for vaginal cuff brachytherapy due to patient anatomy or those who are&#xD;
             at higher risk for pelvic nodal recurrence and pelvic external beam radiotherapy is&#xD;
             preferred over vaginal cuff brachytherapy.&#xD;
&#xD;
          -  Age ≥18 years.&#xD;
&#xD;
          -  ECOG performance status ≤2 (Karnofsky ≥60%).&#xD;
&#xD;
          -  Patients must have undergone total hysterectomy and bilateral salpingo-oophorectomy&#xD;
             with or without pelvic and/or para-aortic lymph node dissection/sampling or sentinel&#xD;
             lymph node (SLN) dissection.&#xD;
&#xD;
          -  Patients with a prior or concurrent malignancy whose natural history or treatment does&#xD;
             not have the potential to interfere with the safety or efficacy assessment of the&#xD;
             investigational regimen are eligible for this trial.&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with an Inflammatory Bowel Disease diagnosis, regardless of disease activity.&#xD;
&#xD;
          -  Patients with current, active disease involving periaortic node(s). This is based on&#xD;
             histologically positive para-aortic node(s) removed at time of surgery.&#xD;
&#xD;
          -  Patients with gross residual disease following surgical resection. Final pathologic&#xD;
             margins must be negative (no tumor on ink). This may also be determined clinically by&#xD;
             the gynecologic oncologist at time of surgery or post-operative imaging if applicable.&#xD;
             Post-operative imaging is not required at time of surgery.&#xD;
&#xD;
          -  Patients who have ever had pelvic radiotherapy prior to entering the study.&#xD;
&#xD;
          -  Patients who are receiving any other investigational agents. Patients who have&#xD;
             received other investigational agents previously who are no longer receiving these&#xD;
             investigational agents may be eligible at the discretion of the PI.&#xD;
&#xD;
          -  Patients with uncontrolled intercurrent illness.&#xD;
&#xD;
          -  Patients with psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Female</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Teresa Meier, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Cincinnati</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>UCCC Clinical Trials Office</last_name>
    <phone>513-584-7698</phone>
    <email>cancer@uchealth.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Teresa Meier, MD</last_name>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Cincinnati Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45219</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>UCCC CTO</last_name>
      <phone>513-584-7698</phone>
      <email>cancer@uchealth.com</email>
    </contact>
    <investigator>
      <last_name>Teresa Meier, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>February 9, 2021</last_update_submitted>
  <last_update_submitted_qc>February 9, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 12, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Cincinnati</investigator_affiliation>
    <investigator_full_name>Teresa Meier</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Endometrial Neoplasms</mesh_term>
  </condition_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/NCT04458402
org study id: UCCC-GYN-20-01
nct id: NCT04458402
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
Studying adjuvant hypofractionated whole pelvis radiation therapy in Endometrial Cancer.
This is a Phase I study evaluating the safety of adjuvant hypofractionated whole pelvis
      radiation therapy (WPRT) in endometrial cancer. The primary objective of the study is to
      determine the maximum tolerated dose per fraction (MTDF), defined by acceptable acute
      clinician-reported GI and GU toxicity and patient-reported GI toxicity, of WPRT from among
      the two study dose levels. Acute GI and GU toxicity will be assessed according to both the
      NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0, and Patient Reported
      Outcome-CTCAE (PRO-CTCAE). Clinician-reported dose-limiting toxicity (C-DLT) is a binary
      outcome (yes/no), defined as an acute grade 3 or higher GI or GU per CTCAE, occurring within
      three months of completing WPRT. Patient-reported DLT (P-DLT) is a binary outcome, defined by
      a GI toxicity with a score of ≥4 on the 5-point scale per PRO-CTCAE, occurring within three
      months of completing WPRT. The MTDF is defined as the minimum of the dose with a C-DLT rate
      closest to the clinician-reported target C-DLT rate of 20% and the dose with a P-DLT rate
      closest to the patient-reported target P-DLT rate of 55%. Toxicity results of NRG-RTOG 1203-
      A Randomized Phase III Study of Standard vs. IMRT Pelvic Radiation for Post-Operative
      Treatment of Endometrial and Cervical Cancer- were used to define the acceptable percentage
      of DLTs. The study will accrue participants in cohorts of size 3. The starting dose level
      will be dose level 1 (41.25 Gy in 15 fx).
allocation: N/A
intervention model: Sequential Assignment
intervention model description: Dose allocation will be based upon a Bayesian continual reassessment method that incorporates patient-reported outcomes (PRO-CRM17), which uses separate models for the probability of C-DLT and the probability of P-DLT, as well as the accumulated C-DLT and P-DLT data at each dose level, to sequentially allocate each new patient cohort.
primary purpose: Treatment
masking: None (Open Label)
measure: Safety profile of hypofractionated, isoeffective whole pelvis radiation regimens for post-operative treatment of endometrial cancer using CTCAE version 5.0 and Patient Reported Outcome-CTCAE.
time frame: 3 months
description: Toxicity profile will be determined by assessment of acute gastrointestinal and genitourinary toxicity during WPRT and 3 months post-radiation using CTCAE version 5.0 and Patient Reported Outcome-CTCAE (PRO-CTCAE). Dose-limiting toxicity (DLT) will be defined as any acute ≥ grade 3 gastrointestinal or genitourinary per CTCAE or a score of ≥4 on the 5-point scale per PRO-CTCAE.
measure: Maximum tolerated dose per fraction (MTDF) of hypofractionated, isoeffective whole pelvis radiation regimens for post-operative treatment of endometrial cancer through CTCAE data and gastrointestinal PRO-CTCAE data.
time frame: 3 months
description: Determination of the MTDF will rely on toxicity data, specifically combined gastrointestinal and genitourinary CTCAE data and gastrointestinal PRO-CTCAE data. MTDF should not exceed >20% of patients having a DLT per CTCAE or >55% of patients having a dose-limiting GI toxicity per PRO-CTCAE. Further details in study design.
measure: Impact of hypofractionated WPRT on patient quality of life using the Functional Assessment of Cancer Therapy-Endometrial version 4.0.
time frame: 3 months
description: Quality of life data will be obtained for exploratory analysis only.
measure: Patient compliance with hypofractionated WPRT, as defined by how many patients are able to complete WPRT without a break in treatment.
time frame: 3 months
description: Patient compliance with radiotherapy will be recorded and used for exploratory analysis only.
arm group label: Hypofractionated Whole-Pelvis Radiotherapy
arm group type: Experimental
description: Hypofractionated WPRT Cohort 1: 41.25 Gy in 15 fx Cohort 2: 38 Gy in 10 fx
intervention type: Radiation
intervention name: Hypofractionated WPRT
description: Cohort 1: 41.25 Gy in 15 fx Cohort 1: 38 Gy in 10 fx
arm group label: Hypofractionated Whole-Pelvis Radiotherapy
criteria: 
gender: Female
gender based: Yes
gender description: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Teresa Meier, MD
role: Principal Investigator
affiliation: University of Cincinnati
last name: UCCC Clinical Trials Office
phone: 513-584-7698
email: cancer@uchealth.com
last name: Teresa Meier, MD
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Cincinnati
investigator full name: Teresa Meier
investigator title: Principal Investigator
mesh term: Endometrial Neoplasms
sharing ipd: No