Recruiting

Phase 3

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

Sponsor:

Proton Collaborative Group

Code:

NCT05856773

Conditions

Breast Cancer

Eligibility Criteria

Sex: Female

Age: 19+

Healthy Volunteers: Not accepted

Interventions

Proton Therapy

Study Details

Brief summary:

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.

Conditions

Breast Cancer

Study ID

NCT05856773

Start date

Mar 21, 2024

Status verified date

Jul, 2026

Completion date

Feb, 2041

Anticipated

Primary completion date

Feb, 2038

Anticipated

Eligibility Criteria

Sex: Female

Age: 19+

Healthy Volunteers: Not accepted

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 Design

Enrollment

276 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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\*\*

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\*\*

Interventions

Proton Therapy

Pencil Beam Scanning (PBS)

Primary outcome measure

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 ]

Central Contacts and Locations

Locations

Mayo Clinic

Recruiting

Scottsdale, Arizona, United States, 85259

Contacts

June Leonard

855-776-0015 (toll free)leonard.june@mayo.edu

Principal Investigator:

Carlos Vargas, MD

California Protons Cancer Therapy Center

Recruiting

San Diego, California, United States, 92121

Contacts

Alexandra Crawford, MPH

858-549-7431 alexandra.crawford@californiaprotons.com

Principal Investigator:

Iain MacEwan, MD

University of Florida Proton Therapy Institute

Recruiting

Jacksonville, Florida, United States, 32206

Contacts

Robin Cacchio

904-588-1460 rcacchio@floridaproton.org

Principal Investigator:

Julie Bradley, MD

Dwoskin Proton Therapy Center

Recruiting

Miami, Florida, United States, 33125

Contacts

Zuzel Rodriguez

305-243-0124 z.rodriguez1@med.miami.edu

Principal Investigator:

Cristiane Takita, MD

Miami Cancer Institute

Recruiting

Miami, Florida, United States, 33176

Contacts

Alex Kudryashev

786-596-2000 alexku@baptisthealth.net

Principal Investigator:

Joseph Panoff, MD

Emory Proton Therapy Center

Recruiting

Atlanta, Georgia, United States, 30308

Contacts

Leann Schilling, MPH, CCRP

404-686-0286 leann.schilling@emory.edu

Principal Investigator:

Sunil Dutta, MD

Maryland Proton Treatment Center

Recruiting

Baltimore, Maryland, United States, 21201

Contacts

Caitlin Eggleston

410-328-7586 caitlineggleston@umm.edu

Principal Investigator:

Elizabeth Nichols, MD

New York Proton Center

Recruiting

New York, New York, United States, 10035

Contacts

Ryan Holder

646-968-9055 rholder@nyproton.com

Principal Investigator:

Isabelle Choi, MD

Inova Schar Cancer Institute

Recruiting

Fairfax, Virginia, United States, 22031

Contacts

Sangeetha Moturi

571-472-0343 sangeetha.moturi@inova.org

Principal Investigator:

Ashish Chawla, MD

More Information

Sponsor

Proton Collaborative Group

Last update posted

Jul 10, 2026

Last verified

Jul, 2026

Keywords

Proton Radiation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Proton Collaborative Group on 2026-07-10.