<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/NCT02999074</url>
  </required_header>
  <id_info>
    <org_study_id>BENEFIT</org_study_id>
    <nct_id>NCT02999074</nct_id>
  </id_info>
  <brief_title>Exercise Interventions for Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy</brief_title>
  <acronym>BENEFIT</acronym>
  <official_title>A Randomized 3-arm Exercise Intervention Trial for Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>German Cancer Research Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University Hospital Heidelberg</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>German Cancer Research Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The BENEFIT-Study is a randomized controlled 3-arm intervention trial investigating the&#xD;
      currently discussed hypothesis that exercise concomitant to chemotherapy (CTx) may have a&#xD;
      beneficial effect on cancer prognosis by boosting the anti-tumoral effect of the cytostatics&#xD;
      or by enhancing therapy compliance. This hypothesis is based on pre-clinical and exploratory&#xD;
      clinical trials. Breast cancer patients scheduled for neoadjuvant CTx will be randomized to&#xD;
      either a resistance training or an aerobic training concomitant to the neoadjuvant CTx, or a&#xD;
      waiting list control group that will get no exercise intervention during neoadjuvant CTx&#xD;
      (i.e. usual care) but will exercise after breast surgery. The primary study endpoint is the&#xD;
      tumor size. Further, the effects of resistance and aerobic exercise on the&#xD;
      clinical-pathologic stage (CPS-EG) score, the pathological complete response (pCR),&#xD;
      tolerability and compliance to CTx, physical fitness, patient reported outcomes such as&#xD;
      fatigue, sleep problems, quality of life, depressive symptoms, anxiety and pain, as well as&#xD;
      cognitive function, and selected biomarkers will be investigated.&#xD;
&#xD;
      A confirmation of the study hypothesis would be a strong argument for patients to engage in&#xD;
      exercise as early as during neoadjuvant CTx. The trial will also provide evidence-based&#xD;
      guidance for patients regarding type and timing of training.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>January 2016</start_date>
  <completion_date type="Anticipated">July 2024</completion_date>
  <primary_completion_date type="Anticipated">July 2023</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>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Tumor size</measure>
    <time_frame>change from baseline (before start of neoadjuvant chemotherapy) to breast surgery</time_frame>
    <description>percentage of change from the maximal diameter of the lesion assessed before neoadjuvant chemotherapy (by mammography or sonography) to the maximal diameter of the tumor assessed after neoadjuvant chemotherapy at breast surgery</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>CPS-EG score</measure>
    <time_frame>at breast surgery</time_frame>
    <description>The Clinical-Pathologic Stage (CPS-EG) score combines clinical tumor stage prior to neoadjuvant therapy (CS), pathological tumor stage after neoadjuvant treatment (PS), estrogen receptor status (E) and grading (G). It has been shown to be a valid prognostic factor to discriminate among patient subgroups with respect to survival after neoadjuvant CTx.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>pCR</measure>
    <time_frame>at breast surgery</time_frame>
    <description>The Pathological Complete Response (pCR) is defined as ypT0/is ypN0 and has been consistently demonstrated to be a good prognostic factor for long-term benefit from neoadjuvant CTx.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fatigue Assessment Questionnaire (FAQ)</measure>
    <time_frame>at baseline, week 9, post-chemotherapy (before breast surgery); months 6 and 12 after breast surgery</time_frame>
    <description>Validated 20-item multidimensional self-assessment questionnaire to assess the physical, affective, and cognitive dimension of cancer-related fatigue</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EORTC QLQ-C30 / BR23</measure>
    <time_frame>at baseline, week 9, post-chemotherapy (before breast surgery); months 6 and 12 after breast surgery</time_frame>
    <description>Validated 30-item self-assessment questionnaire to assess quality of life aspects.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Health Questionnaire for Depression and Anxiety (PHQ-4)</measure>
    <time_frame>at baseline, week 9, post-chemotherapy (before breast surgery); months 6 and 12 after breast surgery</time_frame>
    <description>A validated 4-item screener for depression and anxiety.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pittsburgh Sleep Quality Index (PSQI)</measure>
    <time_frame>at baseline, week 9, post-chemotherapy (before breast surgery); months 6 and 12 after breast surgery</time_frame>
    <description>Validated questionnaire to assess sleep quality and sleep problems.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spiroergometry (VO2max)</measure>
    <time_frame>at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Isometric and isokinetic muscle strength measured by ISOMED 2000</measure>
    <time_frame>at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body mass index</measure>
    <time_frame>at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Self-developed physical activity questionnaire including type, duration, frequency and intensity of sports, cycling,and walking</measure>
    <time_frame>Follow-up (6 months and 12 months after breast surgery)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive function - HVLT-R</measure>
    <time_frame>at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery</time_frame>
    <description>Hopkins Verbal Learning Test - Revised (HVLT-R)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive function - TMT</measure>
    <time_frame>at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery</time_frame>
    <description>Trail Making Test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive function - COWA</measure>
    <time_frame>at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery</time_frame>
    <description>Controlled Oral Word Association</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sleep quality</measure>
    <time_frame>at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery</time_frame>
    <description>Measured with ActiGraph (accelerometry)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sleep efficiency</measure>
    <time_frame>at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery</time_frame>
    <description>Measured with ActiGraph (accelerometry)</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">183</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Resistance exercise</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Aerobic exercise</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Waitlist control</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Resistance exercise</intervention_name>
    <description>The training will take place twice weekly over the course of neoadjuvant CTx at the NCT Heidelberg or in regional qualified centers under supervision and guidance of experienced exercise therapists. The progressive resistance exercise comprises 8 machine-based exercises, each performed in 3 sets, 12 repetitions at 60-80% of one repetition maximum (1-RM).</description>
    <arm_group_label>Resistance exercise</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Aerobic exercise</intervention_name>
    <description>The training will take place twice weekly over the course of neoadjuvant CTx at the NCT Heidelberg or in regional qualified centers under supervision and guidance of experienced exercise therapists. The aerobic exercise will be performed on a cycle ergometer (or alternatively at a treadmill, elliptical, rowing ergometer, or combination) progressing from 60% to 70% VO2max with increasing duration. During weeks 7-18 the goal is to perform an extensive interval training.</description>
    <arm_group_label>Aerobic exercise</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Usual care during neoadjuvant chemotherapy/Exercise after surgery</intervention_name>
    <description>The control group receives no exercise intervention during neoadjuvant CTx, which reflects the usual care condition. To investigate effects of different exercise timing, and to provide those patients also a potential health benefit and reduce drop-out and contamination, the control group will receive 18 weeks resistance or aerobic exercise (according to their personal preferences) after breast cancer surgery.</description>
    <arm_group_label>Waitlist control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women ≥ 18 years of Age&#xD;
&#xD;
          -  Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by&#xD;
             core biopsy&#xD;
&#xD;
          -  Scheduled for neoadjuvant CTx (but not yet started)&#xD;
&#xD;
          -  Confirmed hormone receptor and Her2 status&#xD;
&#xD;
          -  Sufficient German language skills&#xD;
&#xD;
          -  Willing to train at the exercise facilities twice per week&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any physical or mental conditions that would hamper the adherence to the training&#xD;
             programs or the completion of the study procedures&#xD;
&#xD;
          -  Engaging in systematic intense exercise training (at least 1h twice per week)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>National Center for Tumor Diseases (NCT)</name>
      <address>
        <city>Heidelberg</city>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>May 6, 2016</study_first_submitted>
  <study_first_submitted_qc>December 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 21, 2016</study_first_posted>
  <last_update_submitted>February 22, 2023</last_update_submitted>
  <last_update_submitted_qc>February 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>exercise</keyword>
  <keyword>resistance training</keyword>
  <keyword>aerobic training</keyword>
  <keyword>breast cancer</keyword>
  <keyword>neoadjuvant chemotherapy</keyword>
  <keyword>fatigue</keyword>
  <keyword>quality of life</keyword>
  <keyword>tumor response</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast 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/NCT02999074
org study id: BENEFIT
nct id: NCT02999074
lead sponsor: 
collaborator: 
has dmc: No
The BENEFIT-Study is a randomized controlled 3-arm intervention trial investigating the
      currently discussed hypothesis that exercise concomitant to chemotherapy (CTx) may have a
      beneficial effect on cancer prognosis by boosting the anti-tumoral effect of the cytostatics
      or by enhancing therapy compliance. This hypothesis is based on pre-clinical and exploratory
      clinical trials. Breast cancer patients scheduled for neoadjuvant CTx will be randomized to
      either a resistance training or an aerobic training concomitant to the neoadjuvant CTx, or a
      waiting list control group that will get no exercise intervention during neoadjuvant CTx
      (i.e. usual care) but will exercise after breast surgery. The primary study endpoint is the
      tumor size. Further, the effects of resistance and aerobic exercise on the
      clinical-pathologic stage (CPS-EG) score, the pathological complete response (pCR),
      tolerability and compliance to CTx, physical fitness, patient reported outcomes such as
      fatigue, sleep problems, quality of life, depressive symptoms, anxiety and pain, as well as
      cognitive function, and selected biomarkers will be investigated.

      A confirmation of the study hypothesis would be a strong argument for patients to engage in
      exercise as early as during neoadjuvant CTx. The trial will also provide evidence-based
      guidance for patients regarding type and timing of training.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Single (Outcomes Assessor)
measure: Tumor size
time frame: change from baseline (before start of neoadjuvant chemotherapy) to breast surgery
description: percentage of change from the maximal diameter of the lesion assessed before neoadjuvant chemotherapy (by mammography or sonography) to the maximal diameter of the tumor assessed after neoadjuvant chemotherapy at breast surgery
measure: CPS-EG score
time frame: at breast surgery
description: The Clinical-Pathologic Stage (CPS-EG) score combines clinical tumor stage prior to neoadjuvant therapy (CS), pathological tumor stage after neoadjuvant treatment (PS), estrogen receptor status (E) and grading (G). It has been shown to be a valid prognostic factor to discriminate among patient subgroups with respect to survival after neoadjuvant CTx.
measure: pCR
time frame: at breast surgery
description: The Pathological Complete Response (pCR) is defined as ypT0/is ypN0 and has been consistently demonstrated to be a good prognostic factor for long-term benefit from neoadjuvant CTx.
measure: Fatigue Assessment Questionnaire (FAQ)
time frame: at baseline, week 9, post-chemotherapy (before breast surgery); months 6 and 12 after breast surgery
description: Validated 20-item multidimensional self-assessment questionnaire to assess the physical, affective, and cognitive dimension of cancer-related fatigue
measure: EORTC QLQ-C30 / BR23
time frame: at baseline, week 9, post-chemotherapy (before breast surgery); months 6 and 12 after breast surgery
description: Validated 30-item self-assessment questionnaire to assess quality of life aspects.
measure: Patient Health Questionnaire for Depression and Anxiety (PHQ-4)
time frame: at baseline, week 9, post-chemotherapy (before breast surgery); months 6 and 12 after breast surgery
description: A validated 4-item screener for depression and anxiety.
measure: Pittsburgh Sleep Quality Index (PSQI)
time frame: at baseline, week 9, post-chemotherapy (before breast surgery); months 6 and 12 after breast surgery
description: Validated questionnaire to assess sleep quality and sleep problems.
measure: Spiroergometry (VO2max)
time frame: at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery
measure: Isometric and isokinetic muscle strength measured by ISOMED 2000
time frame: at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery
measure: Body mass index
time frame: at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery
measure: Self-developed physical activity questionnaire including type, duration, frequency and intensity of sports, cycling,and walking
time frame: Follow-up (6 months and 12 months after breast surgery)
measure: Cognitive function - HVLT-R
time frame: at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery
description: Hopkins Verbal Learning Test - Revised (HVLT-R)
measure: Cognitive function - TMT
time frame: at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery
description: Trail Making Test
measure: Cognitive function - COWA
time frame: at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery
description: Controlled Oral Word Association
measure: Sleep quality
time frame: at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery
description: Measured with ActiGraph (accelerometry)
measure: Sleep efficiency
time frame: at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery
description: Measured with ActiGraph (accelerometry)
arm group label: Resistance exercise
arm group type: Active Comparator
arm group label: Aerobic exercise
arm group type: Active Comparator
arm group label: Waitlist control
arm group type: Other
intervention type: Other
intervention name: Resistance exercise
description: The training will take place twice weekly over the course of neoadjuvant CTx at the NCT Heidelberg or in regional qualified centers under supervision and guidance of experienced exercise therapists. The progressive resistance exercise comprises 8 machine-based exercises, each performed in 3 sets, 12 repetitions at 60-80% of one repetition maximum (1-RM).
arm group label: Resistance exercise
intervention type: Other
intervention name: Aerobic exercise
description: The training will take place twice weekly over the course of neoadjuvant CTx at the NCT Heidelberg or in regional qualified centers under supervision and guidance of experienced exercise therapists. The aerobic exercise will be performed on a cycle ergometer (or alternatively at a treadmill, elliptical, rowing ergometer, or combination) progressing from 60% to 70% VO2max with increasing duration. During weeks 7-18 the goal is to perform an extensive interval training.
arm group label: Aerobic exercise
intervention type: Other
intervention name: Usual care during neoadjuvant chemotherapy/Exercise after surgery
description: The control group receives no exercise intervention during neoadjuvant CTx, which reflects the usual care condition. To investigate effects of different exercise timing, and to provide those patients also a potential health benefit and reduce drop-out and contamination, the control group will receive 18 weeks resistance or aerobic exercise (according to their personal preferences) after breast cancer surgery.
arm group label: Waitlist control
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Breast Neoplasms
sharing ipd: No