Conventionally Fractionated vs. Hypofractionated Comprehensive Nodal Irradiation for Breast Cancer Using Pencil Beam Scanning Proton Therapy (COMPRO)

September 2, 2025 updated by: Proton Collaborative Group

Phase III Randomized Trial of Conventionally Fractionated vs. Hypofractionated COMprehensive Nodal Irradiation for Breast Cancer Using Pencil Beam Scanning PROton Therapy (COMPRO)

The purpose of this research study is to learn more about the effects of using proton radiation therapy delivered over a shorter course of treatment (3 weeks) compared with a longer, standard course of treatment (5 weeks) for women with breast cancer who require radiotherapy to the breast/chest wall and regional lymph nodes.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study is being done to see if comprehensive regional nodal radiation therapy to the breast or chest wall and regional lymph node area using proton therapy delivered with a hypofractionated approach (less treatment days) will result in rates of treatment related skin and soft tissue side effects that are non-inferior compared to conventionally fractionated proton radiotherapy regimens.

Study Type

Interventional

Enrollment (Estimated)

276

Phase

  • Phase 3

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Recruiting
        • Mayo Clinic
        • Contact:
        • Principal Investigator:
          • Carlos Vargas, MD
    • California
      • San Diego, California, United States, 92121
        • Recruiting
        • California Protons Cancer Therapy Center
        • Contact:
        • Principal Investigator:
          • Iain MacEwan, MD
    • Florida
      • Jacksonville, Florida, United States, 32206
        • Recruiting
        • University of Florida Proton Therapy Institute
        • Contact:
        • Principal Investigator:
          • Julie Bradley, MD
      • Miami, Florida, United States, 33176
        • Recruiting
        • Miami Cancer Institute
        • Contact:
        • Principal Investigator:
          • Joseph Panoff, MD
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • Recruiting
        • Emory Proton Therapy Center
        • Contact:
        • Principal Investigator:
          • Sunil Dutta, MD
    • New York
      • New York, New York, United States, 10035
        • Recruiting
        • New York Proton Center
        • Contact:
        • Principal Investigator:
          • Isabelle Choi, MD
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Inova Schar Cancer Institute
        • Contact:
        • Principal Investigator:
          • Ashish Chawla, MD

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with Stage I-III breast cancer who have undergone breast conserving surgery or mastectomy and have been recommended to receive postoperative radiation therapy to the breast or chest wall and regional draining lymph nodes (axilla levels I-III, SCV, IMN)
  • Histologically documented breast cancer (invasive mammary, ductal, medullary, tubular, mucinous, lobular, or ductal carcinoma in situ) for which treatment with radiation therapy to the breast/chest wall and comprehensive regional lymph nodes including the internal mammary chain is recommended
  • Documentation of negative metastatic workup by whole body Positron Emission Tomography - Computed Tomography (PET/CT) or by combined CT of the chest, abdomen, pelvis and Bone scan
  • History and physical exam within 90 days prior to study registration
  • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
  • Negative pregnancy test for women of child-bearing potential
  • Able to begin radiation treatment within 12 weeks of last surgery or last day of chemotherapy
  • Presence of breast implants, breast expanders, tissue flap, or other breast reconstruction are allowed
  • Bilateral breast cancer is allowed if at least one side will be treated with comprehensive nodal irradiation per protocol treatment and will be recorded as the laterality receiving comprehensive nodal irradiation. If both sides will be treated comprehensively, it will be documented as such

Exclusion Criteria:

  • Presence of skin ulceration and / or ipsilateral satellite nodules and/or edema (including peau d'orange) (T4b or T4c disease) or diagnosis of inflammatory breast cancer (T4d disease)
  • Residual gross disease detected by imaging or clinical exam with the exception of <2cm internal mammary lymph node or supraclavicular lymph node amenable to sequential boost
  • Prior history of radiation therapy overlapping with current target volume (including intraoperative brachytherapy, interstitial catheter brachytherapy, balloon brachytherapy, external beam radiation therapy)
  • Prior history of explant surgery or implant removal due to infection or wound healing issues without subsequent implant or flap reconstruction
  • Presence of double/dual port tissue expander
  • Clinical or radiographic evidence of distant metastatic disease
  • Pregnant or breast-feeding females
  • Non-malignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow-up
  • History of connective tissue disorder (i.e., systemic lupus erythematosus, scleroderma), dermatomyositis, xeroderma pigmentosum
  • Known BRCA 1 or BRCA 2 mutation
  • Presence of an active skin rash
  • Prior invasive non-study malignancy unless disease free for ≥ 3 years. Non-melanoma skin cancer, well-differentiated thyroid cancers, in situ carcinomas of the oral cavity, cervix, and other organs, and tumors that are not thought to impact the life expectancy of the patient are permissible.

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: Arm A - Standard Fractionation

50-50.4 Gy (RBE) in 25-28 daily fractions of 1.8-2.0 Gy (RBE) plus a Tumor Bed Boost (for intact breast) of 10 Gy (RBE) in 4-5 daily fractions of 2-2.5 Gy (RBE)

**Additional boost of 10-20 Gy (RBE) in 2-2.5 Gy (RBE) fractions to clinically involved lymph nodes or chest wall/scar allowed at the treating physician's discretion**
Radiation: Proton Therapy
Pencil Beam Scanning (PBS)
Other: Arm B - Hypofractionation

40.05 Gy (RBE) in 15 daily fractions of 2.67 Gy (RBE) plus a Tumor Bed Boost (for intact breast) of 10 Gy (RBE) in 4-5 daily fractions of 2-2.5 Gy (RBE)

**Additional boost of 10-20 Gy (RBE) in 2-2.5 Gy (RBE) fractions to clinically involved lymph nodes or chest wall/scar allowed at the treating physician's discretion**
Radiation: Proton Therapy
Pencil Beam Scanning (PBS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To determine if the rate of grade ≥3 treatment-related skin and soft tissue toxicities with comprehensive nodal irradiation for breast cancer using hypofractionated PBS proton therapy is non-inferior to conventionally-fractionated proton radiotherapy
Time Frame: 2 years after radiation therapy
This study will investigate if adjuvant comprehensive regional nodal radiotherapy to the breast or chest wall and regional lymph nodes including the axilla (levels I-III), supraclavicular (SCV), and internal mammary (IMN) lymph nodes using pencil beam scanning proton therapy delivered with a hypofractionated regimen results in rates of acute and late grade 3 or worse treatment-related skin and soft tissue toxicities that are non-inferior compared with rates in pencil beam scanning proton therapy using conventionally fractionated regimens.
2 years after radiation therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To determine the rate of any grade ≥3 treatment-related adverse events
Time Frame: 2, 5, and 10 years after radiation therapy
2, 5, and 10 years after radiation therapy
To determine local recurrence rates
Time Frame: 2, 5, and 10 years after radiation therapy
2, 5, and 10 years after radiation therapy
To determine regional recurrence rates
Time Frame: 2, 5, and 10 years after radiation therapy
2, 5, and 10 years after radiation therapy
To determine distant recurrence rates
Time Frame: 2, 5, and 10 years after radiation therapy
2, 5, and 10 years after radiation therapy
To determine breast cancer-specific survival
Time Frame: 2, 5, and 10 years after radiation therapy
2, 5, and 10 years after radiation therapy
To determine overall survival
Time Frame: 2, 5, and 10 years after radiation therapy
2, 5, and 10 years after radiation therapy
To assess patient-reported quality of life
Time Frame: 2, 5, and 10 years after radiation therapy
FACT-B questionnaire
2, 5, and 10 years after radiation therapy
To assess patient-reported quality of life
Time Frame: 2, 5, and 10 years after radiation therapy
BREAST-Q questionnaire
2, 5, and 10 years after radiation therapy
To assess physician-reported cosmetic outcomes
Time Frame: 2, 5, and 10 years after radiation therapy
Physician reported cosmesis form
2, 5, and 10 years after radiation therapy

Other Outcome Measures

Outcome Measure
Time Frame
To correlate dosimetric parameters with acute and late adverse events for the development of model dose constraints for comprehensive nodal irradiation for breast cancer using a moderately hypofractionated regimen with PBS-PT
Time Frame: 2, 5, and 10 years after radiation therapy
2, 5, and 10 years after radiation therapy

Collaborators and Investigators

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

Sponsor

Proton Collaborative Group

Investigators

  • Study Chair: Isabelle Choi, MD, Proton Collaborative Group

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)

March 21, 2024

Primary Completion (Estimated)

February 1, 2038

Study Completion (Estimated)

February 1, 2041

Study Registration Dates

First Submitted

April 1, 2023

First Submitted That Met QC Criteria

May 3, 2023

First Posted (Actual)

May 12, 2023

Study Record Updates

Last Update Posted (Estimated)

September 9, 2025

Last Update Submitted That Met QC Criteria

September 2, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BRE009-23

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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