Ultrahypofractionation and Normal Tissue Toxicity

Sponsor

Massachusetts General Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05912231

Collaborator

National Cancer Institute (NCI) (NIH), American Society of Clinical Oncology (Other)

Enrollment

Location

Arms

23.6

Anticipated Duration (Months)

2.1

Patients Per Site Per Month

Study Details

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)

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Breast Cancer Female Breast Cancer Stage II Breast Cancer Stage III Myocardial Fibrosis	Radiation: Accelerated Proton Beam Radiation Therapy (PBT) Radiation: Accelerated Photon Radiation Therapy (XRT)	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Oct 1, 2023

Anticipated Primary Completion Date :

Sep 17, 2025

Anticipated Study Completion Date :

Sep 17, 2025

Arms and Interventions

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: Optional Cardiac PET (Positron Emission Tomography) scan within 8 weeks of starting radiation therapy. 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, photographic imaging, and optional Cardiac PET scan. 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: Optional Cardiac PET (Positron Emission Tomography) scan within 8 weeks of starting radiation therapy. 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, photographic imaging, and optional Cardiac PET scan. 12 month follow up visit with questionnaires and photographic imaging.	Radiation: Accelerated Photon Radiation Therapy (XRT) per protocol

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: Optional Cardiac PET (Positron Emission Tomography) scan within 8 weeks of starting radiation therapy. 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, photographic imaging, and optional Cardiac PET scan. 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

Radiation: Accelerated Photon Radiation Therapy (XRT)

per protocol

Outcome Measures

Primary Outcome Measures

Change in Myocardial Fibrosis from Baseline in Proton Beam Radiation Therapy (PBT) [Up to 7 months (pre-treatment period to 6 month follow up)]
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 [Up to 7 months (pre-treatment period to 6 month follow up)]
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 [Up to 7 months (pre-treatment period to 6 month follow up)]
Cardiac Biomarkers will be measured using enzyme-linked immunoassay (ELISA).
Change in Myocardial Blood Flow at Rest and Stress [Up to 11 months (8 weeks pre-treatment period + 6 months + 3 month window)]
Myocardial flow reserve will be calculated as the ratio stress/rest MBF. Assessed by rest and stress regional and global myocardial blood flow (MBF) by PET scan in absolute value of mL/min/cc and will be calculated by tracer kinetic analysis. Participants will undergo 2 consecutive myocardial perfusion imaging (MPI) scans: a rest scan and a pharmacologically induced stress scan.
Body Image Evaluation [Up to 13 months (pre-treatment period to 12 month follow up)]
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 [Up to 13 months (pre-treatment period to 12 month follow up)]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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)