Ultrahypofractionation and Normal Tissue Toxicity

Proton Versus Photon Ultrahypofractionated Radiation Therapy and Its Impact on Normal Tissue

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)

Study Overview

• Status: Recruiting
• Conditions: Myocardial Fibrosis; Breast Cancer; Breast Cancer Stage II; Breast Cancer Female; Breast Cancer Stage III
• Intervention / Treatment: Radiation: Accelerated Proton Beam Radiation Therapy (PBT); Radiation: Accelerated 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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rachel Jimenez, MD; Phone Number: 617-726-8651; Email: RBJIMENEZ@PARTNERS.ORG

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Massachusetts General Hospital Cancer Center
      • Contact: Rachel Jimenez, MD; Phone Number: 617-726-8651; Email: RBJIMENEZ@PARTNERS.ORG

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Accelerated Proton Beam Radiation Therapy (PBT) Group; 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.	Radiation: Accelerated Proton Beam Radiation Therapy (PBT); per protocol
Experimental: Accelerated Photon Radiation Therapy (XRT) Group; 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.	Radiation: Accelerated Photon Radiation Therapy (XRT); per protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 7 months (pre-treatment period to 6 month follow up)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Up to 7 months (pre-treatment period to 6 month follow up)
Stability of Cardiac Biomarkers from Baseline	Cardiac Biomarkers will be measured using enzyme-linked immunoassay (ELISA).	Up to 7 months (pre-treatment period to 6 month follow up)
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).	Up to 13 months (pre-treatment period to 12 month follow up)
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.	Up to 13 months (pre-treatment period to 12 month follow up)

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Cancer Institute (NCI); American Society of Clinical Oncology
• Investigators: Principal Investigator: Rachel Jimenez, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2023
• Primary Completion (Estimated): September 17, 2025
• Study Completion (Estimated): September 17, 2025

Study Registration Dates

• First Submitted: June 12, 2023
• First Submitted That Met QC Criteria: June 12, 2023
• First Posted (Actual): June 22, 2023

Study Record Updates

• Last Update Posted (Actual): January 12, 2024
• Last Update Submitted That Met QC Criteria: January 11, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Breast Cancer; Breast Cancer Stage II; Radiation Therapy; Myocardial Fibrosis; Breast Cancer Stage III; Breast Cancer Female; XRT; PBT; Proton Beam Radiation Therapy; Photon Radiation Therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Fibrosis; Breast Neoplasms
• Other Study ID Numbers: 23-182; P01CA261669 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes