<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/NCT03819985</url>
  </required_header>
  <id_info>
    <org_study_id>2018-0616</org_study_id>
    <secondary_id>NCI-2018-03436</secondary_id>
    <secondary_id>2018-0616</secondary_id>
    <nct_id>NCT03819985</nct_id>
  </id_info>
  <brief_title>Shorter Course, Hypofractionated Pre-Surgery Radiation Therapy in Treating Patients With Localized, Resectable Soft Tissue Sarcoma of the Extremity of Superficial Trunk</brief_title>
  <official_title>Prospective Trial of Hypofractionated Pre-Operative Radiation Therapy for Localized, Resectable Soft Tissue Sarcoma of the Extremity or Superficial Trunk (HYPORT-STS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies the wound complication risk of shorter course, hypofractionated&#xD;
      pre-surgery radiation therapy in treating patients with localized soft tissue sarcoma of the&#xD;
      extremity of superficial trunk that can be removed by surgery. Hypofractionated radiation&#xD;
      therapy delivers higher doses of radiation therapy over a shorter period of time and may kill&#xD;
      more tumor cells and have fewer side effects. Shorter course hypofractionated pre surgery&#xD;
      radiation therapy may be more convenient for patients with soft tissue sarcoma than a longer&#xD;
      course of radiation therapy, and may result in fewer complications.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine, in patients with localized, resectable soft tissue sarcoma, whether there is&#xD;
      a non-inferior major wound complication rate for patients receiving 42.75 Gy in 15 fractions&#xD;
      over 3 weeks compared to historical controls who received 50 Gy in conventional fractionation&#xD;
      over 5-6 weeks.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To determine whether local control rates among patients treated with 42.75 Gy in 15&#xD;
      fractions is similar to that observed in previous studies for patients treated with 50 Gy in&#xD;
      conventional fractionation over 5-6 weeks.&#xD;
&#xD;
      II. To determine whether patterns of local relapse, relapse free survival, overall survival,&#xD;
      or metastatic disease free survival for patients treated with 42.75 Gy in 15 fractions are&#xD;
      similar to previously reported studies.&#xD;
&#xD;
      III. To determine where there is a difference in pathologic response in tumor specimens&#xD;
      treated with 42.75 Gy in 15 fractions compared to previously reported rates of hyalinization,&#xD;
      fibrosis, or necrosis.&#xD;
&#xD;
      IV. To explore quality of life, as measured by the Functional Assessment of Cancer&#xD;
      Therapy-General (FACT-G), financial toxicity as measured by the Comprehensive Score for&#xD;
      financial Toxicity (COST) Instrument, and patient reported outcomes, as measured by the&#xD;
      Toronto Extremity Salvage Score (TESS), among individuals undergoing a shorter,&#xD;
      hypofractionated course of pre-operative radiation therapy for soft tissue sarcoma of the&#xD;
      extremity or superficial trunk.&#xD;
&#xD;
      V. To gather subjective data on patient treatment preferences and experiences among&#xD;
      individuals undergoing a shorter, hypofractionated course of pre-operative radiation therapy&#xD;
      for soft tissue sarcoma of the extremity or superficial trunk.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive hypofractionated radiation therapy in 15 daily fractions over 3 weeks in the&#xD;
      absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 3-4 months for 2 years,&#xD;
      every 6 months for 3 years, and then every year for up to 10 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 17, 2018</start_date>
  <completion_date type="Anticipated">August 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2024</primary_completion_date>
  <phase>Phase 2</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>Time to a major wound complication (MWC)</measure>
    <time_frame>Up to 120 days after surgery</time_frame>
    <description>A Bayesian approach for the analysis of a stopping rule of higher acute wound complications for the new dose (E) will be employed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Local recurrence free survival</measure>
    <time_frame>Up to 10 years after radiation therapy</time_frame>
    <description>The data from long-term follow-up will be analyzed for the local recurrence free survival. Kaplan-Meier curves will be generated of survival estimates. We will compare these to historical controls.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease free survival (DFS) time</measure>
    <time_frame>Up to 10 years after radiation therapy</time_frame>
    <description>The data from long-term follow-up will be analyzed for disease-free survival. Kaplan-Meier curves will be generated of survival estimates. Will compare these to historical controls.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to relapse</measure>
    <time_frame>Up to 10 years after radiation therapy</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease specific survival time</measure>
    <time_frame>Up to 10 years after radiation therapy</time_frame>
    <description>Kaplan-Meier curves will be generated of survival estimates.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pattern of local relapse (in radiation field, margin of field, out of radiation field)</measure>
    <time_frame>Up to 10 years after radiation therapy</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of acute toxicity other than MWC</measure>
    <time_frame>Up to 120 days after radiation therapy</time_frame>
    <description>Acute toxicity will be documented and rates tabulated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of late onset toxicity</measure>
    <time_frame>Up to 120 days after radiation therapy</time_frame>
    <description>Late radiation toxicity will be documented and rates tabulated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional outcomes</measure>
    <time_frame>Up to 10 years after radiation therapy</time_frame>
    <description>Limb function and overall patient quality of life/functional status will be documented according to the Musculoskeletal Tumor Society (MSTS) and Toronto Extremity Salvage Score (TESS) and Euroqol-5D (EQ5D), which will be summarized and analyzed as a continuous variable. Differences between mean scores will be tested using the Mann-Whitney test. Mean and median and their 95% confidence interval (CI) will be presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life</measure>
    <time_frame>Up to 10 years after radiation therapy</time_frame>
    <description>Limb function and overall patient quality of life/functional status will be documented according to the MSTS and TESS and Euroqol-5D (EQ5D), which will be summarized and analyzed as a continuous variable. Differences between mean scores will be tested using the Mann-Whitney test. Mean and median and their 95% CI will be presented.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">122</enrollment>
  <condition>Resectable Soft Tissue Sarcoma</condition>
  <condition>Stage I Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8</condition>
  <condition>Stage IA Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8</condition>
  <condition>Stage IB Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8</condition>
  <condition>Stage II Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8</condition>
  <condition>Stage III Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8</condition>
  <condition>Stage IIIA Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8</condition>
  <condition>Stage IIIB Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8</condition>
  <arm_group>
    <arm_group_label>Treatment (hypofractionated RT)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive hypofractionated radiation therapy in 15 daily fractions over 3 weeks in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Hypofractionated Radiation Therapy</intervention_name>
    <description>Undergo hypofractionated RT</description>
    <arm_group_label>Treatment (hypofractionated RT)</arm_group_label>
    <other_name>Hypofractionated Radiotherapy</other_name>
    <other_name>Hypofractionated</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Quality-of-Life Assessment</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Treatment (hypofractionated RT)</arm_group_label>
    <other_name>Quality of Life Assessment</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaire Administration</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Treatment (hypofractionated RT)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Tumor located in the soft tissues of the extremities or superficial trunk&#xD;
&#xD;
          -  Deemed a candidate for complete macroscopic resection of the primary sarcoma&#xD;
&#xD;
          -  Histologically confirmed sarcoma arising in soft tissue&#xD;
&#xD;
          -  Patient may have had excisional biopsy of all gross disease at an outside facility&#xD;
             with positive or uncertain resection margins and still be eligible if the evaluating&#xD;
             sarcoma surgeon in the participating institution recommends oncologic re-resection of&#xD;
             the surgical bed to obtain negative margins after a course of neoadjuvant irradiation&#xD;
             (a sandwich approach of marginal excision--&gt;radiation therapy(RT)--&gt; wide excision, as&#xD;
             per our standard practice)&#xD;
&#xD;
          -  No evidence of nodal or distant metastases as determined by clinical examination or&#xD;
             any form of imaging&#xD;
&#xD;
          -  Has provided written informed consent for participation in this trial&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 3 or less&#xD;
&#xD;
          -  Life expectancy greater than 6 months&#xD;
&#xD;
          -  Patients capable of childbearing are using adequate contraception&#xD;
&#xD;
          -  Available for follow-up&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous radiation therapy to the site of the sarcoma or area surrounding it such that&#xD;
             it would be encompassed by the radiation field needed to treat the current sarcoma. In&#xD;
             other words, treatment on this trial would require re-irradiation of tissues&#xD;
&#xD;
          -  Patients with nodal or distant metastases&#xD;
&#xD;
          -  Women who are pregnant&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Beverly A Guadagnolo</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>MD Anderson Cancer Center</description>
  </link>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>January 25, 2019</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>July 20, 2023</last_update_submitted>
  <last_update_submitted_qc>July 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 24, 2023</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>Sarcoma</mesh_term>
  </condition_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/NCT03819985
org study id: 2018-0616
secondary id: NCI-2018-03436
secondary id: 2018-0616
nct id: NCT03819985
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies the wound complication risk of shorter course, hypofractionated
      pre-surgery radiation therapy in treating patients with localized soft tissue sarcoma of the
      extremity of superficial trunk that can be removed by surgery. Hypofractionated radiation
      therapy delivers higher doses of radiation therapy over a shorter period of time and may kill
      more tumor cells and have fewer side effects. Shorter course hypofractionated pre surgery
      radiation therapy may be more convenient for patients with soft tissue sarcoma than a longer
      course of radiation therapy, and may result in fewer complications.
PRIMARY OBJECTIVES:

      I. To determine, in patients with localized, resectable soft tissue sarcoma, whether there is
      a non-inferior major wound complication rate for patients receiving 42.75 Gy in 15 fractions
      over 3 weeks compared to historical controls who received 50 Gy in conventional fractionation
      over 5-6 weeks.

      SECONDARY OBJECTIVES:

      I. To determine whether local control rates among patients treated with 42.75 Gy in 15
      fractions is similar to that observed in previous studies for patients treated with 50 Gy in
      conventional fractionation over 5-6 weeks.

      II. To determine whether patterns of local relapse, relapse free survival, overall survival,
      or metastatic disease free survival for patients treated with 42.75 Gy in 15 fractions are
      similar to previously reported studies.

      III. To determine where there is a difference in pathologic response in tumor specimens
      treated with 42.75 Gy in 15 fractions compared to previously reported rates of hyalinization,
      fibrosis, or necrosis.

      IV. To explore quality of life, as measured by the Functional Assessment of Cancer
      Therapy-General (FACT-G), financial toxicity as measured by the Comprehensive Score for
      financial Toxicity (COST) Instrument, and patient reported outcomes, as measured by the
      Toronto Extremity Salvage Score (TESS), among individuals undergoing a shorter,
      hypofractionated course of pre-operative radiation therapy for soft tissue sarcoma of the
      extremity or superficial trunk.

      V. To gather subjective data on patient treatment preferences and experiences among
      individuals undergoing a shorter, hypofractionated course of pre-operative radiation therapy
      for soft tissue sarcoma of the extremity or superficial trunk.

      OUTLINE:

      Patients receive hypofractionated radiation therapy in 15 daily fractions over 3 weeks in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3-4 months for 2 years,
      every 6 months for 3 years, and then every year for up to 10 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Time to a major wound complication (MWC)
time frame: Up to 120 days after surgery
description: A Bayesian approach for the analysis of a stopping rule of higher acute wound complications for the new dose (E) will be employed.
measure: Local recurrence free survival
time frame: Up to 10 years after radiation therapy
description: The data from long-term follow-up will be analyzed for the local recurrence free survival. Kaplan-Meier curves will be generated of survival estimates. We will compare these to historical controls.
measure: Disease free survival (DFS) time
time frame: Up to 10 years after radiation therapy
description: The data from long-term follow-up will be analyzed for disease-free survival. Kaplan-Meier curves will be generated of survival estimates. Will compare these to historical controls.
measure: Time to relapse
time frame: Up to 10 years after radiation therapy
measure: Disease specific survival time
time frame: Up to 10 years after radiation therapy
description: Kaplan-Meier curves will be generated of survival estimates.
measure: Pattern of local relapse (in radiation field, margin of field, out of radiation field)
time frame: Up to 10 years after radiation therapy
measure: Incidence of acute toxicity other than MWC
time frame: Up to 120 days after radiation therapy
description: Acute toxicity will be documented and rates tabulated.
measure: Incidence of late onset toxicity
time frame: Up to 120 days after radiation therapy
description: Late radiation toxicity will be documented and rates tabulated.
measure: Functional outcomes
time frame: Up to 10 years after radiation therapy
description: Limb function and overall patient quality of life/functional status will be documented according to the Musculoskeletal Tumor Society (MSTS) and Toronto Extremity Salvage Score (TESS) and Euroqol-5D (EQ5D), which will be summarized and analyzed as a continuous variable. Differences between mean scores will be tested using the Mann-Whitney test. Mean and median and their 95% confidence interval (CI) will be presented.
measure: Quality of life
time frame: Up to 10 years after radiation therapy
description: Limb function and overall patient quality of life/functional status will be documented according to the MSTS and TESS and Euroqol-5D (EQ5D), which will be summarized and analyzed as a continuous variable. Differences between mean scores will be tested using the Mann-Whitney test. Mean and median and their 95% CI will be presented.
arm group label: Treatment (hypofractionated RT)
arm group type: Experimental
description: Patients receive hypofractionated radiation therapy in 15 daily fractions over 3 weeks in the absence of disease progression or unacceptable toxicity.
intervention type: Radiation
intervention name: Hypofractionated Radiation Therapy
description: Undergo hypofractionated RT
arm group label: Treatment (hypofractionated RT)
other name: Hypofractionated Radiotherapy
other name: Hypofractionated
intervention type: Other
intervention name: Quality-of-Life Assessment
description: Ancillary studies
arm group label: Treatment (hypofractionated RT)
other name: Quality of Life Assessment
intervention type: Other
intervention name: Questionnaire Administration
description: Ancillary studies
arm group label: Treatment (hypofractionated RT)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Beverly A Guadagnolo
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
country: United States
url: http://www.mdanderson.org
description: MD Anderson Cancer Center
responsible party type: Sponsor
mesh term: Sarcoma