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

NCT05856773 | Recruiting Phase 3 DMC

• 1 other identifier: BRE009-23
• Study Type: interventional
• Target: 276
• Locations: 1 country
• Sites: 7

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

Keywords

Proton Radiation

Outcome Measures

Primary Outcomes (1)

• 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

  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 Outcomes (9)

• To determine the rate of any grade ≥3 treatment-related adverse events

  2, 5, and 10 years after radiation therapy

• To determine local recurrence rates

  2, 5, and 10 years after radiation therapy

• To determine regional recurrence rates

  2, 5, and 10 years after radiation therapy

• To determine distant recurrence rates

  2, 5, and 10 years after radiation therapy

• To determine breast cancer-specific survival

  2, 5, and 10 years after radiation therapy

Other Outcomes (1)

• 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

  2, 5, and 10 years after radiation therapy

Study Arms (2)

Arm A - Standard Fractionation

ACTIVE COMPARATOR

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

Arm B - Hypofractionation

OTHER

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

Interventions

Proton Therapy RADIATION

Pencil Beam Scanning (PBS)

Arm A - Standard Fractionation; Arm B - Hypofractionation

Eligibility Criteria

• Age: 19 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Proton Collaborative Group: lead

Study Sites (7)

Mayo Clinic

Scottsdale, Arizona, 85259, United States

RECRUITING

California Protons Cancer Therapy Center

San Diego, California, 92121, United States

RECRUITING

University of Florida Proton Therapy Institute

Jacksonville, Florida, 32206, United States

RECRUITING

Miami Cancer Institute

Miami, Florida, 33176, United States

RECRUITING

Emory Proton Therapy Center

Atlanta, Georgia, 30308, United States

RECRUITING

New York Proton Center

New York, New York, 10035, United States

RECRUITING

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Proton Therapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Heavy Ion Radiotherapy; Radiotherapy; Therapeutics

Study Officials

• Isabelle Choi, MD

  Proton Collaborative Group

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2023
• First Posted: May 12, 2023
• Study Start: March 21, 2024
• Primary Completion (Estimated): February 1, 2038
• Study Completion (Estimated): February 1, 2041
• Last Updated: September 9, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)