Back to resultsUltrahypofractionation and Normal Tissue Toxicity
Primary Purpose
Breast Cancer, Breast Cancer Female, Breast Cancer Stage II
Status
Not yet recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Accelerated Proton Beam Radiation Therapy (PBT)
Accelerated Photon Radiation Therapy (XRT)
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring Radiation Therapy, Photon Radiation Therapy, XRT, Proton Beam Radiation Therapy, PBT, Breast Cancer, Breast Cancer Female, Breast Cancer Stage II, Breast Cancer Stage III, Myocardial Fibrosis
Eligibility Criteria
Inclusion Criteria: ≥18 years of age Non-metastatic Breast Cancer patients who are scheduled to receive conventional left-sided or bilateral breast/chest wall RT inclusive of treatment to the internal mammary lymph nodes (IMNs) Prior chemotherapy is permitted Ability to understand and the willingness to sign a written informed consent document No contraindication to MRI Patients with right-sided breast cancer or patients with left-sided patients not requiring treatment to the IMNs, but where cardiac anatomy is determined to be unfavorable by the study PI, will be considered eligible. Exclusion Criteria: Person who is pregnant or breastfeeding. Patients receiving any other investigational agent will not be excluded from study eligibility, unless the patient is already enrolled in an interventional study evaluating cardiac toxicity. No cytotoxic therapy or radiotherapy may be used during radiation therapy. Contra-indication to gadolinium contrast (e.g., chronic kidney disease) Contra-indication to radiotherapy (e.g., scleroderma, p53 mutation)
Sites / Locations
- Massachusetts General Hospital Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Accelerated Proton Beam Radiation Therapy (PBT) Group
Accelerated Photon Radiation Therapy (XRT) Group
Arm Description
Participants will be randomized 1:1 to XRT group and stratified by receipt of chemotherapy and cardiac risk factors and will complete: Cardiac MRI and blood tests within 1 month prior to start of radiation therapy. Radiation therapy 1x daily for 5 days over 1 week. End of radiation therapy visit with blood tests. 6 month follow up visit with cardiac MRI, blood tests, questionnaires, and photographic imaging. 12 month follow up visit with questionnaires and photographic imaging.
Participants will be randomized 1:1 to XRT group and stratified by receipt of chemotherapy and cardiac risk factors and will complete: Cardiac MRI and blood tests within 1 month prior to start of radiation therapy. Radiation therapy 1x daily for 5 days over 1 week. End of radiation therapy visit with blood tests. 6 month follow up visit with cardiac MRI, blood tests, questionnaires, and photographic imaging. 12 month follow up visit with questionnaires and photographic imaging.
Outcomes
Primary Outcome Measures
Change in Myocardial Fibrosis from Baseline in Proton Beam Radiation Therapy (PBT)
The primary outcome is to determine whether participants who receive accelerated PBT show no increase in myocardial fibrosis on Cardiac MRI (CMR) compared to an estimated 4% increase in extracellular matrix volume fraction (ECV) in participants who receive accelerated XRT. CMR will be performed using a 3T system (Skyra, Siemens). The T1 phase on MRI will be used to measure ECV.
Secondary Outcome Measures
Change in Global Longitudinal Strain (GLS) on CMR from Baseline
GLS will be measured using feature tracking from the Steady-state free precession (SSFP) MRI cine images (Medis Suite, Leiden).
Stability of Cardiac Biomarkers from Baseline
Cardiac Biomarkers will be measured using enzyme-linked immunoassay (ELISA).
Body Image Evaluation
Assessed by photographic imaging of the breast, chest wall and reconstructed breast, the Breast Q: Mastectomy Module (Postoperative) 2.0, the Breast Q: Reconstruction Module (Postoperative) 2.0, and the Breast-Q: Breast Conserving Therapy Module (Postoperative) 2.0 questionnaires which are rigorous patient-report outcome measures. Modules grade Quality of Life (QOL) and Satisfaction Domains related to post-operative care and experiences. All BREAST-Q scales are transformed into scores that range from 0-100. T. A higher score means greater satisfaction or better QOL (depending on the scale).
Change in Shoulder Function from Baseline
Assessed by the Thoracic Focused Assessment with Sonography for Trauma, Triage, and Tracking (TFAST), the Penn Shoulder Scale (PSS), and the Disabilities of the Arm, Shoulder and Hand (DASH) Shoulder Function Scale. TFAST is an objective and highly reproducible functional assessment tool of the arm and shoulder. The PSS is a patient-reported outcome tool which provides a shoulder-specific metric and distinguishes between finer levels of functioning. Scores range from 0 to 100 with a score of 100 indicating low pain, high satisfaction, and high function. DASH is a 30-item, validated, patient-reported scale that captures upper extremity functionality and mobility and maintains high construct validity and responsiveness in the breast cancer population. Questions are graded on a Likert scale with scores ranging from "1" Strongly Disagree to "5" Strongly Agree, where a cumulative score of 0 is graded no disability and 100 is most severe disability.
Full Information
NCT ID
NCT05912231
First Posted
June 12, 2023
Last Updated
October 20, 2023
Sponsor
Massachusetts General Hospital
Collaborators
National Cancer Institute (NCI), American Society of Clinical Oncology
1. Study Identification
Unique Protocol Identification Number
NCT05912231
Brief Title
Ultrahypofractionation and Normal Tissue Toxicity
Official Title
Proton Versus Photon Ultrahypofractionated Radiation Therapy and Its Impact on Normal Tissue
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
September 17, 2025 (Anticipated)
Study Completion Date
September 17, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
National Cancer Institute (NCI), American Society of Clinical Oncology
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This research is being done to see if proton beam radiation therapy (PBT) results in fewer changes to a participant's heart measured with MRI-imaging than conventional or "photon" radiation therapy (XRT) for participants with non-metastatic left sided breast cancer.
The names of the two study groups in this research study are:
Proton Radiation Therapy (PBT)
Conventional or "Photon" Radiation Therapy (XRT)
Detailed Description
This is a randomized phase II trial comparing participants with stage II-III breast cancer treated with accelerated Proton Beam Radiation Therapy (PBT) versus accelerated conventional photon radiation therapy (XRT) inclusive of the regional lymph nodes.
Participants will be randomized into one of two study groups: proton beam radiation therapy versus photon radiation therapy. Randomization means that participants are put into a group by chance.
Study procedures includes screening for eligibility, study treatment visits, Cardiac Magnetic Resonance Imaging (MRI), blood tests, and questionnaires.
The National Cancer Institute, American Society of Clinical Oncology, and Claflin Grant are supporting this research by providing funding for the research study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Breast Cancer Female, Breast Cancer Stage II, Breast Cancer Stage III, Myocardial Fibrosis
Keywords
Radiation Therapy, Photon Radiation Therapy, XRT, Proton Beam Radiation Therapy, PBT, Breast Cancer, Breast Cancer Female, Breast Cancer Stage II, Breast Cancer Stage III, Myocardial Fibrosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Accelerated Proton Beam Radiation Therapy (PBT) Group
Arm Type
Experimental
Arm Description
Participants will be randomized 1:1 to XRT group and stratified by receipt of chemotherapy and cardiac risk factors and will complete:
Cardiac MRI and blood tests within 1 month prior to start of radiation therapy.
Radiation therapy 1x daily for 5 days over 1 week.
End of radiation therapy visit with blood tests.
6 month follow up visit with cardiac MRI, blood tests, questionnaires, and photographic imaging.
12 month follow up visit with questionnaires and photographic imaging.
Arm Title
Accelerated Photon Radiation Therapy (XRT) Group
Arm Type
Experimental
Arm Description
Participants will be randomized 1:1 to XRT group and stratified by receipt of chemotherapy and cardiac risk factors and will complete:
Cardiac MRI and blood tests within 1 month prior to start of radiation therapy.
Radiation therapy 1x daily for 5 days over 1 week.
End of radiation therapy visit with blood tests.
6 month follow up visit with cardiac MRI, blood tests, questionnaires, and photographic imaging.
12 month follow up visit with questionnaires and photographic imaging.
Intervention Type
Radiation
Intervention Name(s)
Accelerated Proton Beam Radiation Therapy (PBT)
Intervention Description
per protocol
Intervention Type
Radiation
Intervention Name(s)
Accelerated Photon Radiation Therapy (XRT)
Intervention Description
per protocol
Primary Outcome Measure Information:
Title
Change in Myocardial Fibrosis from Baseline in Proton Beam Radiation Therapy (PBT)
Description
The primary outcome is to determine whether participants who receive accelerated PBT show no increase in myocardial fibrosis on Cardiac MRI (CMR) compared to an estimated 4% increase in extracellular matrix volume fraction (ECV) in participants who receive accelerated XRT. CMR will be performed using a 3T system (Skyra, Siemens). The T1 phase on MRI will be used to measure ECV.
Time Frame
Up to 7 months (pre-treatment period to 6 month follow up)
Secondary Outcome Measure Information:
Title
Change in Global Longitudinal Strain (GLS) on CMR from Baseline
Description
GLS will be measured using feature tracking from the Steady-state free precession (SSFP) MRI cine images (Medis Suite, Leiden).
Time Frame
Up to 7 months (pre-treatment period to 6 month follow up)
Title
Stability of Cardiac Biomarkers from Baseline
Description
Cardiac Biomarkers will be measured using enzyme-linked immunoassay (ELISA).
Time Frame
Up to 7 months (pre-treatment period to 6 month follow up)
Title
Body Image Evaluation
Description
Assessed by photographic imaging of the breast, chest wall and reconstructed breast, the Breast Q: Mastectomy Module (Postoperative) 2.0, the Breast Q: Reconstruction Module (Postoperative) 2.0, and the Breast-Q: Breast Conserving Therapy Module (Postoperative) 2.0 questionnaires which are rigorous patient-report outcome measures. Modules grade Quality of Life (QOL) and Satisfaction Domains related to post-operative care and experiences. All BREAST-Q scales are transformed into scores that range from 0-100. T. A higher score means greater satisfaction or better QOL (depending on the scale).
Time Frame
Up to 13 months (pre-treatment period to 12 month follow up)
Title
Change in Shoulder Function from Baseline
Description
Assessed by the Thoracic Focused Assessment with Sonography for Trauma, Triage, and Tracking (TFAST), the Penn Shoulder Scale (PSS), and the Disabilities of the Arm, Shoulder and Hand (DASH) Shoulder Function Scale. TFAST is an objective and highly reproducible functional assessment tool of the arm and shoulder. The PSS is a patient-reported outcome tool which provides a shoulder-specific metric and distinguishes between finer levels of functioning. Scores range from 0 to 100 with a score of 100 indicating low pain, high satisfaction, and high function. DASH is a 30-item, validated, patient-reported scale that captures upper extremity functionality and mobility and maintains high construct validity and responsiveness in the breast cancer population. Questions are graded on a Likert scale with scores ranging from "1" Strongly Disagree to "5" Strongly Agree, where a cumulative score of 0 is graded no disability and 100 is most severe disability.
Time Frame
Up to 13 months (pre-treatment period to 12 month follow up)
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
All women of all races and ethnic groups are eligible for this trial.
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
≥18 years of age
Non-metastatic Breast Cancer patients who are scheduled to receive conventional left-sided or bilateral breast/chest wall RT inclusive of treatment to the internal mammary lymph nodes (IMNs)
Prior chemotherapy is permitted
Ability to understand and the willingness to sign a written informed consent document
No contraindication to MRI
Patients with right-sided breast cancer or patients with left-sided patients not requiring treatment to the IMNs, but where cardiac anatomy is determined to be unfavorable by the study PI, will be considered eligible.
Exclusion Criteria:
Person who is pregnant or breastfeeding.
Patients receiving any other investigational agent will not be excluded from study eligibility, unless the patient is already enrolled in an interventional study evaluating cardiac toxicity. No cytotoxic therapy or radiotherapy may be used during radiation therapy.
Contra-indication to gadolinium contrast (e.g., chronic kidney disease)
Contra-indication to radiotherapy (e.g., scleroderma, p53 mutation)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Rachel Jimenez, MD
Phone
617-726-8651
Email
RBJIMENEZ@PARTNERS.ORG
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rachel Jimenez, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital Cancer Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rachel Jimenez, MD
Phone
617-726-8651
Email
RBJIMENEZ@PARTNERS.ORG
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
IPD Sharing Time Frame
Data can be shared no earlier than 1 year following the date of publication
IPD Sharing Access Criteria
Contact the Partners Innovations team at http://www.partners.org/innovation
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Ultrahypofractionation and Normal Tissue Toxicity
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