<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/NCT03788213</url>
  </required_header>
  <id_info>
    <org_study_id>2018/TMC/133/IRB/31</org_study_id>
    <nct_id>NCT03788213</nct_id>
  </id_info>
  <brief_title>One Week Versus Three Week in Adjuvant Radiotherapy in Breast Cancer</brief_title>
  <acronym>HYPORTAdjuvant</acronym>
  <official_title>HYPOfractionated Radiation Therapy Comparing a Standard Radiotherapy Schedule (Over Three Weeks) With a Novel One Week Schedule in Adjuvant Breast Cancer: An Open Label Randomised Controlled Study (HYPORT- Adjuvant)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tata Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Christian Medical College, Vellore, India</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sanjay Gandhi Postgraduate Institute of Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Tata Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Background:Moderate three week hypofractionated adjuvant radiotherapy schedule is a standard&#xD;
      care in breast cancers. A five day schedule has been demonstrated to be iso-toxic as a&#xD;
      standard three week schedule. Recently studies have also demonstrated the safety and&#xD;
      feasibility of simultaneous integrated boost in this setting. This randomized trial will&#xD;
      investigate if a one-week course of hypofractionated breast radiotherapy is non-inferior to a&#xD;
      three week course.&#xD;
&#xD;
      Aim: To determine if one-week schedule of adjuvant radiotherapy in breast cancer is&#xD;
      non-inferior to a three week schedule.&#xD;
&#xD;
      Primary Objective: Locoregional Recurrence Rate (LRR) (Cumulative proportion of patients with&#xD;
      locoregional recurrence) at 5 years&#xD;
&#xD;
      Secondary Objective:&#xD;
&#xD;
        1. Overall survival (OS) (Time from randomization to death)&#xD;
&#xD;
        2. Invasive Disease-free survival (iDFS) (Time from randomization to any invasive disease&#xD;
           recurrence, death due to any cause or second invasive malignancy)&#xD;
&#xD;
        3. Late adverse events (AE)&#xD;
&#xD;
        4. Quality of Life (QoL)&#xD;
&#xD;
      Hypothesis:&#xD;
&#xD;
        1. 1 week schedule will be non-inferior to a three week schedule for Locoregional&#xD;
           Recurrence Rate&#xD;
&#xD;
        2. 1 week schedule will be non-inferior to a three week schedule for OS&#xD;
&#xD;
        3. 1 week schedule will be not result in worse late adverse events as compared to 3 week&#xD;
           schedule&#xD;
&#xD;
        4. Proportion of patients decrease in quality of life will not differ between the two arms&#xD;
           at 12 months&#xD;
&#xD;
      Design: Open-label, parallel group, two arm, randomised, phase III, non-inferiority trial.&#xD;
&#xD;
      Population: Patients with breast cancer who need adjuvant radiotherapy after breast&#xD;
      conservation or mastectomy.&#xD;
&#xD;
      Intervention: Patients will be randomized to 15 days or 5 days of radiotherapy to the whole&#xD;
      breast or chest wall or reconstructed breast. Nodal radiation will be delivered as indicated.&#xD;
      A simultaneous integrated boost (SIB) will be delivered to patients who need a tumor bed&#xD;
      boost after breast cancer. The following dose schedules will be tested:&#xD;
&#xD;
      Control Group: 40 Gy in 15 fractions over 3 weeks (with SIB of 8 Gy)*&#xD;
&#xD;
      Test Group: 26 Gy in 5 fractions over 1 week (with SIB of 6 Gy).*&#xD;
&#xD;
      * Use of Sequential Boost is allowed in both arms if prespecified by the institution. If used&#xD;
      dose is 12 Gy in 4 fractions in 1 week in both arms.&#xD;
&#xD;
      Outcomes and measures:&#xD;
&#xD;
        1. LRR : Cumulative proportion of patients with ipsilateral Locoregional Recurrence after&#xD;
           treatment at 5 years .&#xD;
&#xD;
        2. OS: Time from randomization to the time of death due to any cause. Cumulative proportion&#xD;
           reported at 5 years.&#xD;
&#xD;
        3. iDFS: Time from randomization to any disease recurrence, death due to any cause or&#xD;
           second primary invasive cancer.Cumulative proportion reported at 5 years.&#xD;
&#xD;
        4. AE: Proportion of patients with late Grade 2 or more AE as defined by the CTCAE 5&#xD;
           criteria&#xD;
&#xD;
        5. QoL: Proportion of patients with a worse summary score in the EORTC QLQ C30 at 12 months&#xD;
           post-treatment as compared to the baseline score.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 26, 2019</start_date>
  <completion_date type="Anticipated">March 26, 2029</completion_date>
  <primary_completion_date type="Anticipated">March 26, 2029</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Randomised, controlled, open-label, two arm, multicenter, randomized controlled trial with two parallel groups</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Locoregional Recurrence Rate (LRR)</measure>
    <time_frame>5 years</time_frame>
    <description>Cumulative proportion of patients with locoregional recurrence</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS )</measure>
    <time_frame>5 Years</time_frame>
    <description>Time from randomization to the time of death due to any cause. Cumulative proportion reported at 5 years</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Invasive Disease Free Survival ( iDFS )</measure>
    <time_frame>5 Years</time_frame>
    <description>Time from randomization to any disease recurrence, death due to any cause or second primary invasive cancer. Cumulative proportion reported at 5 years.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Event ( AE )</measure>
    <time_frame>5 Years</time_frame>
    <description>Proportion of patients with late Grade 2 or more AE as defined by the CTCAE 5 criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life ( QoL )</measure>
    <time_frame>12 months</time_frame>
    <description>Proportion of patients with a worse summary score in the health related quality of life as measured using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ C30) at 12 months post-treatment as compared to the baseline score. The total summary score may range between 0 - 100 with higher scores indicating better health related quality of life. This score is the mean of the 13 of the 15 items of the EORTC QLQ C30 questionnaire which include the scores related to all the domains excepting the Global quality of life scale and Financial impact scale.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">2100</enrollment>
  <condition>Breast Cancer Female</condition>
  <arm_group>
    <arm_group_label>3 week RT</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Adjuvant Radiotherapy delivered over 3 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>1 Week RT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Adjuvant Radiotherapy delivered over 1 week</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>3 week RT</intervention_name>
    <description>40 Gy in 15 fractions over 3 weeks to the whole breast or chest wall. Patients undergoing breast conservation therapy will receive additional boost radiotherapy to the tumor bed. The supraclavicular fossa will be treated in patient with node positive disease or those receiving neoadjuvant chemotherapy. IMC and Axillary radiotherapy will be given as per the institutional policy. Boost Dose schedule for BCS patients will be 8 Gy delivered in 15 fractions simultaneously with tangential EBRT. In institutions planning for sequential boost, a dose of 12 Gy in 4 fractions will be delivered after whole breast EBRT.</description>
    <arm_group_label>3 week RT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>1 week RT</intervention_name>
    <description>26 Gy in 5 fractions over 1 week to the whole breast or chest wall. Treatment volumes will be same as the control arm. Additional boost will be delivered to patients who have undergone breast conservation. Boost Dose schedule for BCS patients will be 6 Gy delivered in 5 fractions simultaneously with tangential EBRT. In institutions planning for sequential boost, a dose of 12 Gy in 4 fractions will be delivered after whole breast EBRT.</description>
    <arm_group_label>1 Week RT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically confirmed invasive breast cancers&#xD;
&#xD;
          -  Age &gt; 18 years&#xD;
&#xD;
          -  ECOG performance status : 0 - 3&#xD;
&#xD;
          -  Underwent curative intent surgery for the breast cancer with complete microscopic&#xD;
             resection either in the form of a mastectomy or breast conservation surgery&#xD;
&#xD;
          -  Adequate axillary clearance or a validated sentinel node biopsy procedure. For the&#xD;
             purpose of this study, adequacy of the axillary clearance will be determined by a&#xD;
             multidisciplinary tumor board and rationale for the decision documented in the case&#xD;
             records. As a general guideline, at least 10 axillary lymph nodes need to be sampled&#xD;
             for an axillary nodal dissection to be considered as adequate.&#xD;
&#xD;
          -  Absence of distant metastases. Patients who have high risk breast cancer as defined by&#xD;
             a Nottingham Prognostic Index (NPI) of &gt; 5.4 will be considered for metastatic workup&#xD;
             in the form of a 18 FDG PET CT. Alternatively, a CT scan of the thorax and whole&#xD;
             abdomen, and a bone scan is also allowed. Metastatic workup will also be recommended&#xD;
             in patients with AJCC 8 T3/T4 tumors at presentation, 4 or more nodes positive after&#xD;
             surgery (pN2 or above). Patients with low or intermediate NPI will be considered for&#xD;
             metastatic workup on a case by case basis. Metastatic workup will also be recommended&#xD;
             for all patients undergoing neoadjuvant chemotherapy for locally advanced breast&#xD;
             cancers.&#xD;
&#xD;
          -  Clear margins of resection for the breast primary as defined by absence tumor on ink&#xD;
             in the specimen if a breast conservation has been performed or excision upto the deep&#xD;
             fascia of the pectoralis major or skin.&#xD;
&#xD;
          -  Adjuvant radiotherapy is indicated. The following patients will be considered as&#xD;
             candidates to receive adjuvant radiotherapy:&#xD;
&#xD;
          -  All patients after breast conservation surgery or after neoadjuvant chemotherapy&#xD;
&#xD;
          -  Patients after mastectomy if any of the below:&#xD;
&#xD;
               -  T3 - T4 tumors&#xD;
&#xD;
               -  more than 3 axillary lymph nodes&#xD;
&#xD;
               -  T0-T2 tumor with 0 - 3 axillary lymph nodes with a Cambridge Score of 3 or more.&#xD;
&#xD;
          -  The SCF will be included in patients with axillary nodal involvement in pathology or&#xD;
             in those patients who have undergone neoadjuvant chemotherapy. The internal mammary&#xD;
             nodes will be included based on the institutional policy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of any one of the following will exclude the patient from participation in&#xD;
             the study:&#xD;
&#xD;
          -  Patients with pure ductal carcinomas in situ (in patients undergoing upfront surgery).&#xD;
&#xD;
          -  Patients with non-epithelial malignant conditions of the breast viz. Sarcomas,&#xD;
             lymphomas, phyllodes tumors&#xD;
&#xD;
          -  Patients with metaplastic breast cancers&#xD;
&#xD;
          -  Presence of pathologically proven residual supraclavicular nodal metastases or&#xD;
             residual internal mammary lymphadenopathy at time of radiotherapy.&#xD;
&#xD;
          -  Prior radiotherapy to the ipsilateral breast/chest wall or the mediastinum. Patients&#xD;
             with synchronous / metachronous contralateral breast malignancies will be eligible for&#xD;
             inclusion. Patients requiring bilateral breast radiotherapy are also eligible for&#xD;
             inclusion.&#xD;
&#xD;
          -  Concurrent illness, including severe infection that may jeopardize the ability of the&#xD;
             patient to undergo the procedures outlined in this protocol with reasonable safety&#xD;
&#xD;
          -  Serious medical or psychiatric conditions that might limit the ability of the patient&#xD;
             to comply with the protocol.&#xD;
&#xD;
          -  Patients planned for concurrent chemotherapy during radiation therapy. Concurrent&#xD;
             hormonal therapy or targeted therapy using anti-HER2 agents is allowed.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Only Female with Breast Cancer</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Sanjoy Chatterjee, FRCR</last_name>
    <phone>9038161825</phone>
    <phone_ext>7403</phone_ext>
    <email>sanjoy.chatterjee@tmckolkata.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Sanjoy Chatterjee</name>
      <address>
        <city>Kolkata</city>
        <state>West Bengal</state>
        <zip>700160</zip>
        <country>India</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sanjoy Chatterjee, FRCR</last_name>
      <phone>9038161825</phone>
      <phone_ext>7403</phone_ext>
      <email>sanjoy.chatterjee@tmckolkata.com</email>
    </contact>
    <contact_backup>
      <last_name>Sanjoy Chatterjee, FRCR</last_name>
      <phone>9038161825</phone>
      <phone_ext>7403</phone_ext>
      <email>chatterjee72@hotmail.com</email>
    </contact_backup>
    <investigator>
      <last_name>Rosina Ahmed, FRCS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Santam Chakraborty, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Sandip Ganguly, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Debdeep Dey, FRCPath</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Anurupa Mahata, MSC Physics</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Abha Kumari, DNB</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Selvamani Bakianathan, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Patricia Solomon, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Rajesh Balakrishnan, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Punita Lal, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Shagun Misra, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>KJ Maria Das, Phd</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>December 26, 2018</study_first_submitted>
  <study_first_submitted_qc>December 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 27, 2018</study_first_posted>
  <last_update_submitted>December 2, 2021</last_update_submitted>
  <last_update_submitted_qc>December 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 17, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hypo-fractionated Radiotherapy,</keyword>
  <keyword>One week Radiotherapy</keyword>
  <keyword>Simultaneous integrated boost</keyword>
  <keyword>Breast Cancer</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/NCT03788213
org study id: 2018/TMC/133/IRB/31
nct id: NCT03788213
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Background:Moderate three week hypofractionated adjuvant radiotherapy schedule is a standard
      care in breast cancers. A five day schedule has been demonstrated to be iso-toxic as a
      standard three week schedule. Recently studies have also demonstrated the safety and
      feasibility of simultaneous integrated boost in this setting. This randomized trial will
      investigate if a one-week course of hypofractionated breast radiotherapy is non-inferior to a
      three week course.

      Aim: To determine if one-week schedule of adjuvant radiotherapy in breast cancer is
      non-inferior to a three week schedule.

      Primary Objective: Locoregional Recurrence Rate (LRR) (Cumulative proportion of patients with
      locoregional recurrence) at 5 years

      Secondary Objective:

        1. Overall survival (OS) (Time from randomization to death)

        2. Invasive Disease-free survival (iDFS) (Time from randomization to any invasive disease
           recurrence, death due to any cause or second invasive malignancy)

        3. Late adverse events (AE)

        4. Quality of Life (QoL)

      Hypothesis:

        1. 1 week schedule will be non-inferior to a three week schedule for Locoregional
           Recurrence Rate

        2. 1 week schedule will be non-inferior to a three week schedule for OS

        3. 1 week schedule will be not result in worse late adverse events as compared to 3 week
           schedule

        4. Proportion of patients decrease in quality of life will not differ between the two arms
           at 12 months

      Design: Open-label, parallel group, two arm, randomised, phase III, non-inferiority trial.

      Population: Patients with breast cancer who need adjuvant radiotherapy after breast
      conservation or mastectomy.

      Intervention: Patients will be randomized to 15 days or 5 days of radiotherapy to the whole
      breast or chest wall or reconstructed breast. Nodal radiation will be delivered as indicated.
      A simultaneous integrated boost (SIB) will be delivered to patients who need a tumor bed
      boost after breast cancer. The following dose schedules will be tested:

      Control Group: 40 Gy in 15 fractions over 3 weeks (with SIB of 8 Gy)*

      Test Group: 26 Gy in 5 fractions over 1 week (with SIB of 6 Gy).*

      * Use of Sequential Boost is allowed in both arms if prespecified by the institution. If used
      dose is 12 Gy in 4 fractions in 1 week in both arms.

      Outcomes and measures:

        1. LRR : Cumulative proportion of patients with ipsilateral Locoregional Recurrence after
           treatment at 5 years .

        2. OS: Time from randomization to the time of death due to any cause. Cumulative proportion
           reported at 5 years.

        3. iDFS: Time from randomization to any disease recurrence, death due to any cause or
           second primary invasive cancer.Cumulative proportion reported at 5 years.

        4. AE: Proportion of patients with late Grade 2 or more AE as defined by the CTCAE 5
           criteria

        5. QoL: Proportion of patients with a worse summary score in the EORTC QLQ C30 at 12 months
           post-treatment as compared to the baseline score.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomised, controlled, open-label, two arm, multicenter, randomized controlled trial with two parallel groups
primary purpose: Treatment
masking: None (Open Label)
measure: Locoregional Recurrence Rate (LRR)
time frame: 5 years
description: Cumulative proportion of patients with locoregional recurrence
measure: Overall Survival (OS )
time frame: 5 Years
description: Time from randomization to the time of death due to any cause. Cumulative proportion reported at 5 years
measure: Invasive Disease Free Survival ( iDFS )
time frame: 5 Years
description: Time from randomization to any disease recurrence, death due to any cause or second primary invasive cancer. Cumulative proportion reported at 5 years.
measure: Adverse Event ( AE )
time frame: 5 Years
description: Proportion of patients with late Grade 2 or more AE as defined by the CTCAE 5 criteria
measure: Quality of Life ( QoL )
time frame: 12 months
description: Proportion of patients with a worse summary score in the health related quality of life as measured using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ C30) at 12 months post-treatment as compared to the baseline score. The total summary score may range between 0 - 100 with higher scores indicating better health related quality of life. This score is the mean of the 13 of the 15 items of the EORTC QLQ C30 questionnaire which include the scores related to all the domains excepting the Global quality of life scale and Financial impact scale.
arm group label: 3 week RT
arm group type: Active Comparator
description: Adjuvant Radiotherapy delivered over 3 weeks
arm group label: 1 Week RT
arm group type: Experimental
description: Adjuvant Radiotherapy delivered over 1 week
intervention type: Radiation
intervention name: 3 week RT
description: 40 Gy in 15 fractions over 3 weeks to the whole breast or chest wall. Patients undergoing breast conservation therapy will receive additional boost radiotherapy to the tumor bed. The supraclavicular fossa will be treated in patient with node positive disease or those receiving neoadjuvant chemotherapy. IMC and Axillary radiotherapy will be given as per the institutional policy. Boost Dose schedule for BCS patients will be 8 Gy delivered in 15 fractions simultaneously with tangential EBRT. In institutions planning for sequential boost, a dose of 12 Gy in 4 fractions will be delivered after whole breast EBRT.
arm group label: 3 week RT
intervention type: Radiation
intervention name: 1 week RT
description: 26 Gy in 5 fractions over 1 week to the whole breast or chest wall. Treatment volumes will be same as the control arm. Additional boost will be delivered to patients who have undergone breast conservation. Boost Dose schedule for BCS patients will be 6 Gy delivered in 5 fractions simultaneously with tangential EBRT. In institutions planning for sequential boost, a dose of 12 Gy in 4 fractions will be delivered after whole breast EBRT.
arm group label: 1 Week RT
criteria: 
gender: Female
gender based: Yes
gender description: Only Female with Breast Cancer
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sanjoy Chatterjee, FRCR
phone: 9038161825
phone ext: 7403
email: sanjoy.chatterjee@tmckolkata.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: India
responsible party type: Sponsor
mesh term: Breast Neoplasms
sharing ipd: No