<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/NCT04443413</url>
  </required_header>
  <id_info>
    <org_study_id>MC1935</org_study_id>
    <secondary_id>NCI-2020-04328</secondary_id>
    <secondary_id>MC1935</secondary_id>
    <secondary_id>P30CA015083</secondary_id>
    <nct_id>NCT04443413</nct_id>
  </id_info>
  <brief_title>Assessing the Rate of Complications in X-Ray Therapy Versus Proton Beam Radiation Therapy After Breast Conserving Surgery or Mastectomy in Treating Patients With Breast Cancer</brief_title>
  <official_title>A Phase II Trial of Hypofractionated Radiotherapy to the Whole Breast or Post-Mastectomy Chest Wall Including Regional Nodal Irradiation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Mayo Clinic</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>
      This phase II trial investigates the rate of complications of x-ray therapy versus proton&#xD;
      beam radiation therapy after breast conserving surgery or mastectomy in treating patients&#xD;
      with breast cancer. X-ray therapy is a form of radiation therapy that uses high-energy&#xD;
      radiation from x-rays to kill tumor cells and shrink tumors. Proton beam radiation therapy is&#xD;
      a type of radiation therapy that uses high-energy beams to treat tumors. It is not yet known&#xD;
      what level of complications x-ray therapy or proton beam radiation therapy have in treating&#xD;
      patients with breast cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To determine the 24-month complication rate of 5 fraction radiotherapy compared to 25&#xD;
      fraction radiotherapy.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate acute toxicity that occur up to 180 days after radiation. II. To evaluate late&#xD;
      toxicity that appear or persist 180 days after radiation. III. To estimate the 5-year&#xD;
      locoregional control, invasive disease-free survival, disease-free survival, cause-specific&#xD;
      survival and overall survival.&#xD;
&#xD;
      CORRELATIVE AND EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate patient-reported quality of life outcomes through Mayo Breast Survey, Mayo 10&#xD;
      (Patient-Reported Outcomes [PRO]-Common Terminology Criteria for Adverse Events [CTCAE]), and&#xD;
      Mayo Patient Survey.&#xD;
&#xD;
      II. To evaluate clinical features, treatment technique, dose-volume parameters, histologic&#xD;
      and genetic variants associated with fair and poor cosmetic outcomes or unplanned surgical&#xD;
      intervention.&#xD;
&#xD;
      III. To evaluate the costs and comparative effectiveness of treatment. IV. Compare the use of&#xD;
      photon therapy with spot scanning proton therapy hypo-fractionated whole breast or&#xD;
      post-mastectomy chest wall with regional nodal irradiation.&#xD;
&#xD;
      V. To evaluated cosmetic outcome with patient-reported measures with elements from the Mayo&#xD;
      Breast Patient Survey and panel assess cosmetic outcome with blinded photographs, and the&#xD;
      Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/Radiation Therapy&#xD;
      Oncology Group (RTOG) Cosmesis Scale.&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 2 arms.&#xD;
&#xD;
      ARM I: Within 12 weeks of the last breast cancer surgery or last dose of adjuvant&#xD;
      chemotherapy and no sooner than 14 days since the last chemotherapy, patients undergo x-ray&#xD;
      therapy over 25 fractions in the absence of disease progression or unacceptable toxicity.&#xD;
      Optionally, patients may then receive a 4-fraction boost of x-ray therapy.&#xD;
&#xD;
      ARM II: Within 12 weeks of the last breast cancer surgery or last dose of adjuvant&#xD;
      chemotherapy and no sooner than 14 days since the last chemotherapy, patients undergo proton&#xD;
      beam radiation therapy over 5 fractions in the absence of disease progression or unacceptable&#xD;
      toxicity. Optionally, patients may receive a concurrent 5-fraction boost of proton beam&#xD;
      radiation therapy.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 12 weeks, at 6, 12, 24, and&#xD;
      36 months, and then at 5 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 15, 2020</start_date>
  <completion_date type="Anticipated">June 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2024</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Panel-assessed cosmetic outcome</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Complication rate</measure>
    <time_frame>At 24 months</time_frame>
    <description>Will be defined as the percentage of women evaluable at 24 months who develop one or more of these events: grade 3 or higher late adverse event or unplanned surgeries for cosmetic or treatment related events, including surgeries to remove implant. The complication rate will be estimated using a binomial estimator in both experimental arm and control arm, and a one-sided 90% confidence interval of the difference will be computed with normal approximation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of acute adverse events</measure>
    <time_frame>Up to 90 days post-radiation therapy</time_frame>
    <description>The maximum grade for each type of acute adverse event will be recorded for each patient. Data will be summarized as frequencies and relative frequencies by treatment arm. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Rates will be compared between arms using chi-squared tests.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of late toxicity</measure>
    <time_frame>Up to 5 years post-radiation therapy</time_frame>
    <description>Will be defined as any adverse event that occurred or persisted after the first 180 days post-radiation therapy and up to 5 years post-radiation therapy. The maximum grade for each type of late adverse event will be recorded for each patient. Data will be summarized as frequencies and relative frequencies by treatment arm. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Rates will be compared between arms using chi-squared tests.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Locoregional control</measure>
    <time_frame>Up to 5 years post-radiation therapy</time_frame>
    <description>The cumulative incidence of locoregional recurrence will be estimated using a competing risks method by treatment arm. The competing risks will be distant breast cancer recurrence and death. Comparison between arms will employ Fine-Gray regression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Invasive disease-free survival</measure>
    <time_frame>From study registration until the time of invasive disease recurrence (not including ductal carcinoma in situ) or death due to any cause, assessed up to 5 years post-radiation therapy</time_frame>
    <description>Invasive disease recurrence is defined by ipsilateral breast tumor recurrence (IBTR), regional recurrence, or distant recurrence. Will be estimated with a Kaplan-Meier estimator and curve by treatment arm. Estimates will be given for specific time points along with 95% confidence intervals. Comparison between arms will employ a log-rank test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease-free survival</measure>
    <time_frame>From study registration until the occurrence of IBTR, regional invasive breast cancer recurrence, distant breast cancer recurrence, or death due to any cause, assessed up to 5 years post-radiation therapy</time_frame>
    <description>Will be estimated with a Kaplan-Meier estimator and curve by treatment arm. Estimates will be given for specific time points along with 95% confidence intervals. Comparison between arms will employ a log-rank test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cause-specific survival</measure>
    <time_frame>From registration to death due to breast cancer, assessed up to 5 years post-radiation therapy</time_frame>
    <description>Will be estimated with a Kaplan-Meier estimator and curve by treatment arm. Estimates will be given for specific time points along with 95% confidence intervals. Comparison between arms will employ a log-rank test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From registration to death due to any cause, assessed up to 5 years post-radiation therapy</time_frame>
    <description>Will be estimated with a Kaplan-Meier estimator and curve by treatment arm. Estimates will be given for specific time points along with 95% confidence intervals. Comparison between arms will employ a log-rank test.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Quality of life</measure>
    <time_frame>Up to 5 years post-radiation therapy</time_frame>
    <description>Elements of the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events will be used for patient self-reporting of toxicities. The Breast Cancer Treatment Outcomes Scale will be used to measure patient reported functional status (pain, mobility). The Mayo Breast Patient Survey and Mayo Patient Survey will also be used. These surveys will be used to report patient reported measures such as fatigue, breast pain, breast shape, and arm related morbidity. They will be summarized as the mean +/- standard deviation and median (minimum value, maximum value). Mixed models will be used to estimate changes at fixed time points as well as compare outcomes between arms.</description>
  </other_outcome>
  <other_outcome>
    <measure>Clinical features associated with fair and poor cosmetic outcomes or unplanned surgical intervention</measure>
    <time_frame>Up to 5 years post-radiation therapy</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Treatment technique associated with fair and poor cosmetic outcomes or unplanned surgical intervention</measure>
    <time_frame>Up to 5 years post-radiation therapy</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Dose-volume parameters associated with fair and poor cosmetic outcomes or unplanned surgical intervention</measure>
    <time_frame>Up to 5 years post-radiation therapy</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Histologic variants associated with fair and poor cosmetic outcomes or unplanned surgical intervention</measure>
    <time_frame>Up to 5 years post-radiation therapy</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Genetic variants associated with fair and poor cosmetic outcomes or unplanned surgical intervention</measure>
    <time_frame>Up to 5 years post-radiation therapy</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Costs and comparative effectiveness of treatment</measure>
    <time_frame>Up to 5 years post-radiation therapy</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Comparison of types of treatment</measure>
    <time_frame>Up to 5 years post-radiation therapy</time_frame>
    <description>Will compare the use of photon therapy with spot scanning proton therapy hypo-fractionated whole breast or post-mastectomy chest wall with regional nodal irradiation.</description>
  </other_outcome>
  <other_outcome>
    <measure>Cosmetic outcome</measure>
    <time_frame>Up to 5 years post-radiation therapy</time_frame>
    <description>Will compare cosmetic outcome with patient self-reported and panel-assessed cosmetic outcome measures to include elements from the Mayo Breast Patient Survey, blinded photograph assessment, the modified Harvard/National Surgical Adjuvant Breast and Bowel Project/Radiation Therapy Oncology Group Cosmesis Scale, and the Breast Cancer Treatment Outcome Scale. Will be summarized with the frequencies and confidence intervals of fair or poor cosmesis events at baseline, 2 years, and 5 years by treatment arm. Comparisons between arms will employ chi-squared tests.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">98</enrollment>
  <condition>Anatomic Stage I Breast Cancer AJCC v8</condition>
  <condition>Anatomic Stage IA Breast Cancer AJCC v8</condition>
  <condition>Anatomic Stage IB Breast Cancer AJCC v8</condition>
  <condition>Anatomic Stage II Breast Cancer AJCC v8</condition>
  <condition>Anatomic Stage IIA Breast Cancer AJCC v8</condition>
  <condition>Anatomic Stage IIB Breast Cancer AJCC v8</condition>
  <condition>Anatomic Stage III Breast Cancer AJCC v8</condition>
  <condition>Anatomic Stage IIIA Breast Cancer AJCC v8</condition>
  <condition>Anatomic Stage IIIB Breast Cancer AJCC v8</condition>
  <condition>Anatomic Stage IIIC Breast Cancer AJCC v8</condition>
  <condition>Prognostic Stage I Breast Cancer AJCC v8</condition>
  <condition>Prognostic Stage IA Breast Cancer AJCC v8</condition>
  <condition>Prognostic Stage IB Breast Cancer AJCC v8</condition>
  <condition>Prognostic Stage II Breast Cancer AJCC v8</condition>
  <condition>Prognostic Stage IIA Breast Cancer AJCC v8</condition>
  <condition>Prognostic Stage IIB Breast Cancer AJCC v8</condition>
  <condition>Prognostic Stage III Breast Cancer AJCC v8</condition>
  <condition>Prognostic Stage IIIA Breast Cancer AJCC v8</condition>
  <condition>Prognostic Stage IIIB Breast Cancer AJCC v8</condition>
  <condition>Prognostic Stage IIIC Breast Cancer AJCC v8</condition>
  <arm_group>
    <arm_group_label>Arm I (x-ray therapy)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Within 12 weeks of the last breast cancer surgery or last dose of adjuvant chemotherapy and no sooner than 14 days since the last chemotherapy, patients undergo x-ray therapy over 25 fractions in the absence of disease progression or unacceptable toxicity. Optionally, patients may then receive a 4-fraction boost of x-ray therapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (proton beam radiation therapy)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Within 12 weeks of the last breast cancer surgery or last dose of adjuvant chemotherapy and no sooner than 14 days since the last chemotherapy, patients undergo proton beam radiation therapy over 5 fractions in the absence of disease progression or unacceptable toxicity. Optionally, patients may receive a concurrent 5-fraction boost of proton beam radiation therapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Proton Beam Radiation Therapy</intervention_name>
    <description>Undergo proton beam radiation therapy</description>
    <arm_group_label>Arm II (proton beam radiation therapy)</arm_group_label>
    <other_name>PBRT</other_name>
    <other_name>Proton</other_name>
    <other_name>Proton EBRT</other_name>
    <other_name>Proton External Beam Radiotherapy</other_name>
    <other_name>Proton Radiation Therapy</other_name>
    <other_name>PROTON Therapy</other_name>
    <other_name>Radiation, Proton Beam</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaire Administration</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Arm I (x-ray therapy)</arm_group_label>
    <arm_group_label>Arm II (proton beam radiation therapy)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>X-ray Therapy</intervention_name>
    <description>Undergo x-ray therapy</description>
    <arm_group_label>Arm I (x-ray therapy)</arm_group_label>
    <other_name>X-ray Radiation Therapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt;= 18 years&#xD;
&#xD;
          -  Histological confirmation of breast cancer&#xD;
&#xD;
          -  Breast conserving surgery or mastectomy (reconstruction is allowed)&#xD;
&#xD;
          -  Clinical or pathologic T1-T4c, N0-3, M0 disease&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2&#xD;
&#xD;
          -  Able to and provides Institutional Review Board (IRB) approved study specific written&#xD;
             informed consent&#xD;
&#xD;
          -  Indications for breast or post mastectomy radiation with regional nodal radiotherapy&#xD;
             per the discretion of the treating physician&#xD;
&#xD;
          -  If uncertain of eligibility please consult the principal investigator (PI)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Medical contraindication to receipt of radiotherapy&#xD;
&#xD;
          -  Severe active co-morbid systemic illnesses or other severe concurrent disease which,&#xD;
             in the judgment of the investigator or PI, would make the patient inappropriate for&#xD;
             entry into this study or interfere significantly with the proper assessment of safety&#xD;
             and toxicity of the prescribed regimens&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements or providing informed consent&#xD;
&#xD;
          -  Active systemic lupus or scleroderma&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Prior receipt of ipsilateral breast or chest wall radiation&#xD;
&#xD;
          -  Persistent positive margins on ink after definitive surgery either for ductal&#xD;
             carcinoma in situ (DCIS) or invasive cancer&#xD;
&#xD;
          -  No active metastatic disease from other origin&#xD;
&#xD;
          -  Recurrent breast cancer&#xD;
&#xD;
          -  Patient requires bilateral breast radiation treatment&#xD;
&#xD;
          -  cT4d patients (inflammatory breast cancer)&#xD;
&#xD;
          -  Patients that may not be compliant or fit for the study at the discretion of the PI&#xD;
&#xD;
          -  Male patients&#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>Carlos E Vargas</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Arizona</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85259</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Clinical Trials Referral Office</last_name>
      <phone>855-776-0015</phone>
      <email>mayocliniccancerstudies@mayo.edu</email>
    </contact>
    <investigator>
      <last_name>Carlos E. Vargas, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic in Florida</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224-9980</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Clinical Trials Referral Office</last_name>
      <phone>855-776-0015</phone>
      <email>mayocliniccancerstudies@mayo.edu</email>
    </contact>
    <investigator>
      <last_name>Laura A. Vallow, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic in Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Clinical Trials Referral Office</last_name>
      <phone>855-776-0015</phone>
      <email>mayocliniccancerstudies@mayo.edu</email>
    </contact>
    <investigator>
      <last_name>Robert W. Mutter, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>June 19, 2020</study_first_submitted>
  <study_first_submitted_qc>June 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 23, 2020</study_first_posted>
  <last_update_submitted>June 26, 2023</last_update_submitted>
  <last_update_submitted_qc>June 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 27, 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>Breast Neoplasms</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/NCT04443413
org study id: MC1935
secondary id: NCI-2020-04328
secondary id: MC1935
secondary id: P30CA015083
nct id: NCT04443413
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This phase II trial investigates the rate of complications of x-ray therapy versus proton
      beam radiation therapy after breast conserving surgery or mastectomy in treating patients
      with breast cancer. X-ray therapy is a form of radiation therapy that uses high-energy
      radiation from x-rays to kill tumor cells and shrink tumors. Proton beam radiation therapy is
      a type of radiation therapy that uses high-energy beams to treat tumors. It is not yet known
      what level of complications x-ray therapy or proton beam radiation therapy have in treating
      patients with breast cancer.
PRIMARY OBJECTIVE:

      I. To determine the 24-month complication rate of 5 fraction radiotherapy compared to 25
      fraction radiotherapy.

      SECONDARY OBJECTIVES:

      I. To evaluate acute toxicity that occur up to 180 days after radiation. II. To evaluate late
      toxicity that appear or persist 180 days after radiation. III. To estimate the 5-year
      locoregional control, invasive disease-free survival, disease-free survival, cause-specific
      survival and overall survival.

      CORRELATIVE AND EXPLORATORY OBJECTIVES:

      I. To evaluate patient-reported quality of life outcomes through Mayo Breast Survey, Mayo 10
      (Patient-Reported Outcomes [PRO]-Common Terminology Criteria for Adverse Events [CTCAE]), and
      Mayo Patient Survey.

      II. To evaluate clinical features, treatment technique, dose-volume parameters, histologic
      and genetic variants associated with fair and poor cosmetic outcomes or unplanned surgical
      intervention.

      III. To evaluate the costs and comparative effectiveness of treatment. IV. Compare the use of
      photon therapy with spot scanning proton therapy hypo-fractionated whole breast or
      post-mastectomy chest wall with regional nodal irradiation.

      V. To evaluated cosmetic outcome with patient-reported measures with elements from the Mayo
      Breast Patient Survey and panel assess cosmetic outcome with blinded photographs, and the
      Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/Radiation Therapy
      Oncology Group (RTOG) Cosmesis Scale.

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM I: Within 12 weeks of the last breast cancer surgery or last dose of adjuvant
      chemotherapy and no sooner than 14 days since the last chemotherapy, patients undergo x-ray
      therapy over 25 fractions in the absence of disease progression or unacceptable toxicity.
      Optionally, patients may then receive a 4-fraction boost of x-ray therapy.

      ARM II: Within 12 weeks of the last breast cancer surgery or last dose of adjuvant
      chemotherapy and no sooner than 14 days since the last chemotherapy, patients undergo proton
      beam radiation therapy over 5 fractions in the absence of disease progression or unacceptable
      toxicity. Optionally, patients may receive a concurrent 5-fraction boost of proton beam
      radiation therapy.

      After completion of study treatment, patients are followed up at 12 weeks, at 6, 12, 24, and
      36 months, and then at 5 years.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: Panel-assessed cosmetic outcome
measure: Complication rate
time frame: At 24 months
description: Will be defined as the percentage of women evaluable at 24 months who develop one or more of these events: grade 3 or higher late adverse event or unplanned surgeries for cosmetic or treatment related events, including surgeries to remove implant. The complication rate will be estimated using a binomial estimator in both experimental arm and control arm, and a one-sided 90% confidence interval of the difference will be computed with normal approximation.
measure: Incidence of acute adverse events
time frame: Up to 90 days post-radiation therapy
description: The maximum grade for each type of acute adverse event will be recorded for each patient. Data will be summarized as frequencies and relative frequencies by treatment arm. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Rates will be compared between arms using chi-squared tests.
measure: Incidence of late toxicity
time frame: Up to 5 years post-radiation therapy
description: Will be defined as any adverse event that occurred or persisted after the first 180 days post-radiation therapy and up to 5 years post-radiation therapy. The maximum grade for each type of late adverse event will be recorded for each patient. Data will be summarized as frequencies and relative frequencies by treatment arm. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Rates will be compared between arms using chi-squared tests.
measure: Locoregional control
time frame: Up to 5 years post-radiation therapy
description: The cumulative incidence of locoregional recurrence will be estimated using a competing risks method by treatment arm. The competing risks will be distant breast cancer recurrence and death. Comparison between arms will employ Fine-Gray regression.
measure: Invasive disease-free survival
time frame: From study registration until the time of invasive disease recurrence (not including ductal carcinoma in situ) or death due to any cause, assessed up to 5 years post-radiation therapy
description: Invasive disease recurrence is defined by ipsilateral breast tumor recurrence (IBTR), regional recurrence, or distant recurrence. Will be estimated with a Kaplan-Meier estimator and curve by treatment arm. Estimates will be given for specific time points along with 95% confidence intervals. Comparison between arms will employ a log-rank test.
measure: Disease-free survival
time frame: From study registration until the occurrence of IBTR, regional invasive breast cancer recurrence, distant breast cancer recurrence, or death due to any cause, assessed up to 5 years post-radiation therapy
description: Will be estimated with a Kaplan-Meier estimator and curve by treatment arm. Estimates will be given for specific time points along with 95% confidence intervals. Comparison between arms will employ a log-rank test.
measure: Cause-specific survival
time frame: From registration to death due to breast cancer, assessed up to 5 years post-radiation therapy
description: Will be estimated with a Kaplan-Meier estimator and curve by treatment arm. Estimates will be given for specific time points along with 95% confidence intervals. Comparison between arms will employ a log-rank test.
measure: Overall survival
time frame: From registration to death due to any cause, assessed up to 5 years post-radiation therapy
description: Will be estimated with a Kaplan-Meier estimator and curve by treatment arm. Estimates will be given for specific time points along with 95% confidence intervals. Comparison between arms will employ a log-rank test.
measure: Quality of life
time frame: Up to 5 years post-radiation therapy
description: Elements of the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events will be used for patient self-reporting of toxicities. The Breast Cancer Treatment Outcomes Scale will be used to measure patient reported functional status (pain, mobility). The Mayo Breast Patient Survey and Mayo Patient Survey will also be used. These surveys will be used to report patient reported measures such as fatigue, breast pain, breast shape, and arm related morbidity. They will be summarized as the mean +/- standard deviation and median (minimum value, maximum value). Mixed models will be used to estimate changes at fixed time points as well as compare outcomes between arms.
measure: Clinical features associated with fair and poor cosmetic outcomes or unplanned surgical intervention
time frame: Up to 5 years post-radiation therapy
measure: Treatment technique associated with fair and poor cosmetic outcomes or unplanned surgical intervention
time frame: Up to 5 years post-radiation therapy
measure: Dose-volume parameters associated with fair and poor cosmetic outcomes or unplanned surgical intervention
time frame: Up to 5 years post-radiation therapy
measure: Histologic variants associated with fair and poor cosmetic outcomes or unplanned surgical intervention
time frame: Up to 5 years post-radiation therapy
measure: Genetic variants associated with fair and poor cosmetic outcomes or unplanned surgical intervention
time frame: Up to 5 years post-radiation therapy
measure: Costs and comparative effectiveness of treatment
time frame: Up to 5 years post-radiation therapy
measure: Comparison of types of treatment
time frame: Up to 5 years post-radiation therapy
description: Will compare the use of photon therapy with spot scanning proton therapy hypo-fractionated whole breast or post-mastectomy chest wall with regional nodal irradiation.
measure: Cosmetic outcome
time frame: Up to 5 years post-radiation therapy
description: Will compare cosmetic outcome with patient self-reported and panel-assessed cosmetic outcome measures to include elements from the Mayo Breast Patient Survey, blinded photograph assessment, the modified Harvard/National Surgical Adjuvant Breast and Bowel Project/Radiation Therapy Oncology Group Cosmesis Scale, and the Breast Cancer Treatment Outcome Scale. Will be summarized with the frequencies and confidence intervals of fair or poor cosmesis events at baseline, 2 years, and 5 years by treatment arm. Comparisons between arms will employ chi-squared tests.
arm group label: Arm I (x-ray therapy)
arm group type: Experimental
description: Within 12 weeks of the last breast cancer surgery or last dose of adjuvant chemotherapy and no sooner than 14 days since the last chemotherapy, patients undergo x-ray therapy over 25 fractions in the absence of disease progression or unacceptable toxicity. Optionally, patients may then receive a 4-fraction boost of x-ray therapy.
arm group label: Arm II (proton beam radiation therapy)
arm group type: Experimental
description: Within 12 weeks of the last breast cancer surgery or last dose of adjuvant chemotherapy and no sooner than 14 days since the last chemotherapy, patients undergo proton beam radiation therapy over 5 fractions in the absence of disease progression or unacceptable toxicity. Optionally, patients may receive a concurrent 5-fraction boost of proton beam radiation therapy.
intervention type: Radiation
intervention name: Proton Beam Radiation Therapy
description: Undergo proton beam radiation therapy
arm group label: Arm II (proton beam radiation therapy)
other name: PBRT
other name: Proton
other name: Proton EBRT
other name: Proton External Beam Radiotherapy
other name: Proton Radiation Therapy
other name: PROTON Therapy
other name: Radiation, Proton Beam
intervention type: Other
intervention name: Questionnaire Administration
description: Ancillary studies
arm group label: Arm I (x-ray therapy)
arm group label: Arm II (proton beam radiation therapy)
intervention type: Radiation
intervention name: X-ray Therapy
description: Undergo x-ray therapy
arm group label: Arm I (x-ray therapy)
other name: X-ray Radiation Therapy
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Carlos E Vargas
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
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investigator: 
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status: Recruiting
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country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms