Ultra-Hypofractionated vs. Hypofractionated Radiation for Node-Positive Breast Cancer

NCT06559540 | Recruiting Phase 2 DMC FDA Device

• 1 other identifier: 202407159
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

In breast cancer patients with nodal involvement, numerous studies have demonstrated that adjuvant radiation therapy reduces the risk of local recurrence, regional recurrence, and distant metastases, in addition to improving survival. The dose and fractionation for adjuvant breast radiation therapy has evolved over time, as novel schedules have been compared to the current standard of care. Hypofractionated radiation therapy (266 cGy per fraction x 15-16 fractions over 3 weeks) has been shown to result in equivalent oncologic outcomes, as well as equivalent acute and late toxicity, when compared to standard fractionation (200 cGy per fraction x 25 fractions over 5 weeks). Subsequently, hypofractionated breast radiation has become the current standard of care. More recently, ultra-hypofractionated breast radiation (520 cGy per fraction x 5 fractions over 1 week) was shown in a randomized trial to be non-inferior to hypofractionated radiation when treating the breast after lumpectomy. However, the efficacy and toxicity of using ultra-hypofractionated radiation therapy when also treating the regional nodes has not been reported. This is important, as there is greater radiation exposure to several normal tissues, such as the arm/shoulder, brachial plexus, normal lymphatics, heart, and lung, when treating the regional nodes. In this randomized study, the investigators aim to compare the tolerability and efficacy of ultra-hypofractionated breast/chest wall and regional nodal radiation (SWIFT RT) against hypofractionated radiation (RT). The investigators will evaluate acute and late toxicity, oncologic outcomes (including local recurrence, regional recurrence, distant metastasis, and overall survival), cosmesis, and patient-reported quality of life. The investigators will collect blood samples for correlative studies of biomarkers of fibrosis and cardiac toxicity.

Conditions

Node-positive Breast Cancer

Keywords

Breast cancer; Radiation; Hypofractionation; QOL; Cosmesis; Toxicity

Outcome Measures

Primary Outcomes (1)

• Proportion of patients who are free of serious treatment related late toxicity.

  Toxicities of concern may include lymphedema, radiation pneumonitis, brachial plexopathy, rib fracture, cardiac disease, and breast/chest wall fibrosis.

  Day 91 through 5 year follow-up (estimated to be 5 years and 1 month)

Study Arms (2)

Hypofractionated radiation (RT)

ACTIVE COMPARATOR

Breast/chest wall and nodal radiation (4256 cGy in 16 fractions over 3-4 weeks).

Radiation: Hypofractionated radiation

Ultra-hypofractionated breast/chest wall and regional nodal radiation (SWIFT RT)

EXPERIMENTAL

Breast/chest wall and nodal radiation (2600 cGy in 5 fractions over 1-2 weeks).

Radiation: Ultra-hypofractionated breast/chest wall and regional nodal radiation

Interventions

Hypofractionated radiation RADIATION

External beam photon therapy with IMRT or VMAT to the breast/chestwall and regional lymph nodes, including supraclavicular, infraclavicular, axillary, and internal mammary nodes,

Also known as: RT

Hypofractionated radiation (RT)

Ultra-hypofractionated breast/chest wall and regional nodal radiation RADIATION

External beam photon therapy with IMRT or VMAT to the breast/chestwall and regional lymph nodes, including supraclavicular, infraclavicular, axillary, and internal mammary nodes

Also known as: SWIFT RT

Ultra-hypofractionated breast/chest wall and regional nodal radiation (SWIFT RT)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed invasive carcinoma of the breast. Metaplastic breast cancer is allowed.
• AJCC 8th Edition Stage: cT1-3 primary tumor. cN1-2 or pN1-2.
• Biopsy-proven involved axillary node(s) (either at baseline and/or at time of surgery).
• Undergone either partial mastectomy (with negative final histologic margins (defined as no tumor on ink, after initial surgery or re-excision)) or mastectomy (with negative histologic margins defined as tumor (either invasive or in situ disease) \> 2 mm from the final margin).
• Nodal surgery with either sentinel lymph node biopsy or axillary lymph node dissection. Effort to recover the original biopsy-proven node should be performed at time of surgery.
• Systemic therapy (chemotherapy and/or endocrine therapy) should be administered as per standard of care and recommendation of medical oncology. Neoadjuvant and/or adjuvant systemic therapy is allowed. Concurrent endocrine therapy, anti-HER2 therapy, and immunotherapy during RT is allowed.
• All radiation therapy must be planned to be delivered at BJH or a Siteman satellite location.
• Female.
• Age ≥ 18 years at diagnosis.
• ECOG Zubrod performance status 0 or 1.
• English speaker.
• Able to understand and willing to sign IRB-approved written informed consent document.

You may not qualify if:

• Presence of distant metastases.
• Diagnosis of nonepithelial breast malignancies such as sarcoma or lymphoma.
• Diagnosis of bilateral breast cancer.
• AJCC cT4 disease, pT4 disease, or any skin involvement on exam or pathology, including dermal LVSI.
• Presence of palpable or radiographically suspicious supraclavicular, infraclavicular, or internal mammary nodes.
• Prior radiation therapy which would have any overlap with current radiation therapy plan.
• Diagnosis of prior breast cancer or diagnosis of current breast cancer more than one year prior to enrollment.
• Diagnosis of systemic lupus erythematosis, scleroderma, or dermatomyositis.
• Diagnosis of a coexisting medical condition which limits life expectancy to \< 2 years.
• Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational treatment. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial.
• Time between last breast cancer surgery to RT simulation is greater than 10 weeks, or time between completion of chemotherapy to RT simulation is greater than 8 weeks, whichever is performed last prior to RT.
• Planning to undergo concurrent chemotherapy.
• Pregnancy, which will be excluded prior to simulation.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Radiation Dose Hypofractionation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics

Study Officials

• Maria Thomas, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maria Thomas, M.D., Ph.D.

CONTACT

314-362-8615; mariathomas@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2024
• First Posted: August 19, 2024
• Study Start: August 27, 2024
• Primary Completion (Estimated): April 30, 2034
• Study Completion (Estimated): April 30, 2034
• Last Updated: January 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)