Pragmatic Randomized Trial of Proton vs. Photon Therapy for Patients With Non-Metastatic Breast Cancer: A Radiotherapy Comparative Effectiveness (RADCOMP) Consortium Trial

November 4, 2025 updated by: Abramson Cancer Center at Penn Medicine
A pragmatic randomized clinical trial of patients with locally advanced breast cancer randomized to either proton or photon therapy and followed longitudinally for cardiovascular morbidity and mortality, health-related quality of life, and cancer control outcomes. Quality of life is the outcome measure for the estimated primary completion date of December, 2024, www.radcomp.org.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Because no one knows which radiation treatment is best, if you decide to take part in this study, you will be randomly assigned to 1 of 2 treatment groups, and then you will begin radiation treatment according to usual medical practice. Randomly assigning you to a group helps makes sure that each group has a similar mix of patients and makes the study better - and is only done when doctors are not sure whether one treatment is better than the other. You have an equal chance of getting into either treatment group, like a coin flip. Both you and your doctor will be told which treatment you will get.

No matter which group patients are in, doctors will work very carefully to reduce the radiation to healthy tissues. Both groups will followed for at least 10 years after completing radiation therapy. The results of this study will help decide which radiation is best for future patients with your type of breast cancer.

Study Type

Interventional

Enrollment (Estimated)

1238

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic-Arizona
    • California
      • San Diego, California, United States, 92121
        • UC San Diego
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Georgetown University Medical Center
    • Florida
      • Coral Gables, Florida, United States, 33146
        • University of Miami Sylvester Cancer Center at Coral Gables
      • Deerfield Beach, Florida, United States, 33442
        • University of Miami Sylvester Cancer Center - Deerfield
      • Gainesville, Florida, United States, 32610
        • University of Florida Health
      • Jacksonville, Florida, United States, 32206
        • University of Florida Health Proton Therapy Institute
      • Miami, Florida, United States, 33136
        • University of Miami Sylvester Cancer Center
      • Miami, Florida, United States, 33176
        • Miami Cancer Insititute
      • Orlando, Florida, United States, 32806
        • Orlando Health
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University
    • Illinois
      • Chicago, Illinois, United States, 60190
        • Northwestern Medicine Proton Center
    • Louisiana
      • Shreveport, Louisiana, United States, 71103
        • Willis Knighton
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Danvers, Massachusetts, United States, 01923
        • Mass General/North Shore Cancer Center
    • Michigan
      • Flint, Michigan, United States, 48532
        • McLaren Proton Therapy
      • Royal Oak, Michigan, United States, 48073
        • William Beaumont
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic-Rochester
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Washington University, St. Louis
    • New Jersey
      • Hamilton, New Jersey, United States, 08690
        • RWJ University Hospital Hamilton
      • New Brunswick, New Jersey, United States, 08903
        • Cancer Institute of NJ
      • Somerset, New Jersey, United States, 07728
        • ProCure Proton Therapy Center
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10035
        • New York Proton Center
    • Ohio
      • Cincinnati, Ohio, United States, 45267
        • University of Cincinnati
      • Cleveland, Ohio, United States, 44106
        • University Hospitals, Case Medical Center
      • West Chester, Ohio, United States, 45069
        • University Pointe, University of Cincinnati
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Oklahoma University - Stephenson Cancer Center
    • Pennsylvania
      • Harrisburg, Pennsylvania, United States, 17109
        • Pinnacle Health Cancer Institute
      • Philadelphia, Pennsylvania, United States, 19104
        • Abramson Cancer Center at Penn Medicine
      • West Chester, Pennsylvania, United States, 19380
        • Chester County Hospital
    • Tennessee
      • Knoxville, Tennessee, United States, 37909
        • Thompson Proton Center
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
      • Irving, Texas, United States, 75063
        • Texas Center for Proton Therapy
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Inova Schar Cancer Institute
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington
      • Seattle, Washington, United States, 98133
        • Seattle Cancer Care Alliance

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Females or males diagnosed with pathologically (histologically) proven invasive mammary carcinoma (ductal, lobular or other) of the breast who have undergone either mastectomy or lumpectomy with any type of axillary surgery or axillary sampling.
  • For patients who have undergone lumpectomy, any type of mastectomy and any type of reconstruction (including no reconstruction) are allowed.
  • For patients who have undergone lumpectomy, there are no breast size limitations.
  • Patients with non-metastatic breast cancer are eligible. This includes American Joint Committee on Cancer (AJCC) 7th edition left- or right-sided breast cancer clinical or pathologic stage I, II, III or loco-regionally recurrent at time of diagnosis. For patients that receive neoadjuvant chemotherapy, AJCC 7th edition left- or right-sided breast cancer pathologic stage yp 0, I, II, III are eligible.
  • Bilateral breast cancer is permitted. Patients with bilateral breast cancer will be stratified as left-sided.
  • Must be proceeding with breast/chest wall and nodal radiation therapy including internal mammary node treatment.
  • Must have a pertinent history/physical examination within 90 days prior to registration.
  • Age ≥ 21 years
  • ECOG Performance Status 0 - 2 (asymptomatic to symptomatic but capable of self-care) within 90 days prior to randomization.
  • Confirmation that the patient's health insurance will pay for the treatment in this study (patients may still be responsible for some costs, such as co-pays and deductibles). If the patient's insurance will not cover a specific treatment in this study and the patient still wants to participate, confirmation that the patient would be responsible for paying for any treatment received.
  • Patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count ≥ 200 cells/microliter within 180 days prior to registration as documented in the medical record. HIV testing is not required for eligibility for this protocol.
  • The patient must provide study-specific informed consent prior to study entry.

Exclusion Criteria

  • Definitive clinical or radiologic evidence of metastatic disease, as documented by the treating institution.
  • Prior radiotherapy to the ipsilateral chest wall or ipsilateral breast or thorax. Individuals with prior radiotherapy in the contralateral breast or chest wall are eligible.
  • Any radiation therapy for the currently diagnosed breast cancer prior to randomization.
  • Dermatomyositis with a CPK level above normal or with an active skin rash or scleroderma.
  • Other non-malignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow-up.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Photon
Photon therapy: once a day, 5 days a week, for 5 to 7 weeks
Radiation: Photon
Photon Therapy:once a day, 5 days a week, for 5 to 7 weeks
Active Comparator: Proton
Proton therapy: once a day, 5 days a week, for 5 to 7 weeks
Radiation: Proton
Proton Therapy: once a day, 5 days a week, for 5 to 7 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effectiveness of proton therapy vs. photon therapy
Time Frame: 10 years
Compare the effectiveness of proton vs. photon therapy in reducing major cardiovascular events (MCE), defined as atherosclerotic coronary heart disease or other heart disease death, myocardial infarction, coronary revascularization, or hospitalization for major cardiovascular event (heart failure, valvular disease, arrhythmia, or unstable angina).
10 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Control
Time Frame: 5 years
Compare the non-inferiority of proton vs. photon therapy in reducing ipsilateral breast cancer local-regional recurrence and in reducing any recurrence, defined as the first reported breast cancer recurrence of any type (local-regional or distant or cancer-specific mortality)
5 years
Patient-reported Body Image and Function, Fatigue and Other Measures of Health-related Quality of Life (HRQOL)
Time Frame: 5 years
Compare the effectiveness of proton vs. photon therapy in improving patient-reported body image and function, fatigue and other measures of health-related quality of life (HRQOL) (anxiety, social roles, financial toxicity, general satisfaction) and adverse events.
5 years
Radiation Dose and Quality of Life and Cardiac Toxicity
Time Frame: 5 years
Develop predictive models to examine the association of radiation dose distribution (to heart and other normal tissues) and major cardiovascular events and quality of life outcomes.
5 years
Long Term Survival
Time Frame: 15 years
To assess longer-term rates of breast cancer specific and overall survival and development of second malignancies.
15 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Abramson Cancer Center at Penn Medicine

Collaborators

Patient-Centered Outcomes Research Institute

Investigators

  • Study Chair: Shannon MacDonald, MD, Massachusetts General Hospital
  • Principal Investigator: Alexander Lin, MD, Abramson Cancer Center at Penn Medicine
  • Principal Investigator: Bonnie Ky, MD, Abramson Cancer Center at Penn Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 6, 2016

Primary Completion (Estimated)

November 1, 2036

Study Completion (Estimated)

November 1, 2036

Study Registration Dates

First Submitted

November 9, 2015

First Submitted That Met QC Criteria

November 10, 2015

First Posted (Estimated)

November 11, 2015

Study Record Updates

Last Update Posted (Estimated)

November 6, 2025

Last Update Submitted That Met QC Criteria

November 4, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UPCC 19115

Drug and device information, study documents

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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