Ultra-hypofractionated Whole Breast Irradiation With Lumpectomy Cavity Boost for the Treatment of Stage I-III Breast Cancer

Phase 2 Trial of Ultra-Hypofractionated Whole Breast Irradiation With Concomitant Lumpectomy Cavity Boost

This clinical trial tests how well ultra-hypofractionated (UF) whole breast irradiation (WBI) with lumpectomy cavity boost (CB) works in treating patients with stage I-III breast cancer. Breast conservation therapy (BCT) is the recommended treatment for patients with early stage breast cancer. BCT involves a lumpectomy followed by breast radiation. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. Traditionally, WBI has been given once daily over 5-6 weeks and then those at high-risk for recurrence receive additional radiation (boost) to the lumpectomy cavity daily over 4-8 days. This has now been replaced by moderate hypofractionated radiation. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Although moderate hypofractionated radiation therapy reduces the length of treatment from 6-7 weeks to 3-4 weeks, the length of treatment still remains a barrier for many patients. UF-WBI with CB delivers radiation to the whole breast and the surgical cavity at the same time over 5 daily treatments. Giving UF-WBI with CB may prevent recurrence and prolong survival as well as improve the quality of life in patients with stage I-III breast cancer.

Study Overview

• Status: Recruiting
• Conditions: Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Breast Carcinoma
• Intervention / Treatment: Other: Questionnaire Administration; Procedure: Cone-Beam Computed Tomography; Radiation: Hypofractionated External Beam Radiation Therapy; Radiation: Radiation Boost; Radiation: Whole Breast Irradiation

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the impact of UF-WBI + CB as assessed by patient-reported Global Cosmesis Score (GCS) at 1 year.

SECONDARY OBJECTIVES:

I. To characterize the patient-reported cosmetic appearance of the breast over time, as assessed by GCS.

II. To determine short- and long-term physician-reported cosmetic appearance of the breast, as assessed by GCS.

III. To evaluate the acute and late patient-reported radiation-associated toxicities.

IV. To evaluate the acute and late physician-reported radiation-associated toxicities.

V. To estimate:

Va. 5-year in-breast recurrence; Vb. 5-year distant recurrence; Vc. 5-year disease-free survival (DFS); Vd. 5-year overall survival (OS).

EXPLORATORY OBJECTIVES:

I. To evaluate patient-reported quality-of-life (QoL). II. To evaluate volumetric and dosimetric factors associated with acceptable breast cosmesis.

III. To evaluate volumetric and dosimetric factors associated with acute and late radiation-associated toxicities.

OUTLINE:

Patients undergo UF-WBI with CB once daily (QD) on consecutive business days for up to 5 fractions in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo cone-beam computed tomography (CBCT) prior to each radiation treatment.

After completion of study treatment, patients are followed up at 1 month, 6 months, then annually for up to 5 years.

• Study Type: Interventional
• Enrollment (Estimated): 82
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Arcadia, California, United States, 91007
      • Recruiting
      • City of Hope at Arcadia
      • Principal Investigator: Stephanie M. Yoon
      • Contact: Stephanie M. Yoon; Phone Number: 626-873-5241; Email: styoon@coh.org
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope Medical Center
      • Principal Investigator: Stephanie M. Yoon
      • Contact: Stephanie M. Yoon; Phone Number: 626-873-5241; Email: styoon@coh.org
    • Irvine, California, United States, 92618
      • Not yet recruiting
      • City of Hope at Irvine Lennar
      • Principal Investigator: Stephanie M. Yoon
      • Contact: Stephanie M. Yoon; Phone Number: 626-873-5241; Email: styoon@coh.org
    • Lancaster, California, United States, 93534
      • Recruiting
      • City of Hope Antelope Valley
      • Principal Investigator: Stephanie M. Yoon
      • Contact: Stephanie M. Yoon; Phone Number: 626-873-5241; Email: styoon@coh.org
    • South Pasadena, California, United States, 91030
      • Recruiting
      • City of Hope South Pasadena
      • Principal Investigator: Stephanie M. Yoon
      • Contact: Stephanie M. Yoon; Phone Number: 626-873-5241; Email: styoon@coh.org
    • Torrance, California, United States, 90503
      • Recruiting
      • City of Hope at South Bay
      • Contact: Stephanie Yoon, MD; Phone Number: 626-359-8111; Email: styoon@coh.org
    • Upland, California, United States, 91786
      • Recruiting
      • City of Hope UPLAND
      • Principal Investigator: Stephanie M. Yoon
      • Contact: Stephanie M. Yoon; Phone Number: 626-873-5241; Email: styoon@coh.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Documented informed consent of the participant and/or legally authorized representative
• Age: ≥ 40 years
• Female
• Ability to read and understand English for questionnaires
• Histologically confirmed breast cancer
• Malignancy must be epithelial. Non-epithelial breast malignancies such as lymphoma or sarcoma are not allowed
• Patients must have undergone breast conserving surgery. Re-excision for negative margins is allowed
• Patients must have undergone surgical staging of the axilla (sentinel lymph node biopsy or axillary lymph node dissection)
• Must have at least one-high risk feature that would necessitate a lumpectomy cavity boost by the treating radiation oncologist
• Patient must have physician-reported "Excellent" or "Good" cosmesis post-lumpectomy and prior to radiation therapy based on the 4-point Global Cosmetic Score

• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test

  • If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

Exclusion Criteria:

• Prior radiation to the region of the involved breast that in the opinion of the investigator would preclude breast irradiation
• Pathologically or clinically involved regional lymph nodes necessitating comprehensive regional nodal irradiation that includes the supraclavicular fossa
• Clinically significant uncontrolled illness
• Stage IV breast cancer
• Diagnosis of Paget's disease of the nipple
• Other prior or active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Pregnant or breastfeeding
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (UF-WBI with CB); Patients undergo UF-WBI with CB QD on consecutive business days for up to 5 fractions in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CBCT prior to each radiation treatment.

Other: Questionnaire Administration; Ancillary studies; Procedure: Cone-Beam Computed Tomography; Undergo CBCT; Other Names: Cone Beam CT; Cone Beam Computed Tomography; Radiation: Hypofractionated External Beam Radiation Therapy; Undergo UF-WBI with CB; Radiation: Radiation Boost; Undergo UF-WBI with CB; Other Names: Boost Radiation; Boost Radiation Therapy; Boost Radiotherapy; Radiation Therapy Boost; Radiotherapy Boost; BOOST; Radiation: Whole Breast Irradiation; Undergo UF-WBI with CB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	Responding patients are defined as patients with a rating of either "excellent" or "good" on the 4-point Global Cosmesis Score (GCS). Will be estimated along with the 95% exact binomial confidence interval.	At 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported cosmetic outcome using GCS - Baseline	For continuous variables, descriptive statistics such as number, mean, standard deviation, standard error, median (range) etc. will be provided.	At baseline
Patient-reported cosmetic outcome using GCS - 6 months	For continuous variables, descriptive statistics such as number, mean, standard deviation, standard error, median (range) etc. will be provided.	At 6 months
Patient-reported cosmetic outcome using GCS - 1 year	For continuous variables, descriptive statistics such as number, mean, standard deviation, standard error, median (range) etc. will be provided.	At 1 year
Patient-reported cosmetic outcome using GCS - 2 years	For continuous variables, descriptive statistics such as number, mean, standard deviation, standard error, median (range) etc. will be provided.	At 2 years
Patient-reported cosmetic outcome using GCS - 3 years	For continuous variables, descriptive statistics such as number, mean, standard deviation, standard error, median (range) etc. will be provided.	At 3 years
Physician-reported cosmetic outcome using GCS	For continuous variables, descriptive statistics such as number, mean, standard deviation, standard error, median (range) etc. will be provided. For categorical variables, counts and percentages will be provided.	At baseline, at 6 months and at years 1, 2, and 3
Patient-reported radiation-associated toxicities	Will be assessed and graded using Patient-Reported Outcome Common Terminology Criteria for Adverse Events. Observed toxicities will be summarized by type, severity, and attribution. For continuous variables, descriptive statistics such as number, mean, standard deviation, standard error, median (range) etc. will be provided. For categorical variables, counts and percentages will be provided.	At 1 month, 6 months, and 1 year
Physician-reported radiation-associated toxicities	Will be assessed and graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Observed toxicities will be summarized by type, severity, and attribution. For continuous variables, descriptive statistics such as number, mean, standard deviation, standard error, median (range) etc. will be provided. For categorical variables, counts and percentages will be provided.	At 1 month, 6 months, and years 1, 2, and 3
Incidence of in-breast disease recurrence	Will be evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. For continuous variables, descriptive statistics such as number, mean, standard deviation, standard error, median (range) etc. will be provided. For categorical variables, counts and percentages will be provided.	Up to 5 years
Incidence of metastatic disease	Will be evaluated using RECIST criteria. For continuous variables, descriptive statistics such as number, mean, standard deviation, standard error, median (range) etc. will be provided. For categorical variables, counts and percentages will be provided.	Up to 5 years
Disease free survival	Will be estimated using the Kaplan-Meier method with Greenwood variance estimator and 95% confidence interval will be constructed based on log-log transformation.	From start of treatment to in-breast recurrence, metastatic disease, or death from any cause, whichever occurs first, assessed up to 5 years
Overall survival	Will be estimated using the Kaplan-Meier method with Greenwood variance estimator and 95% confidence interval will be constructed based on log-log transformation.	From start of treatment to death from any cause, assessed up to 5 years

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Stephanie M Yoon, City of Hope Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2025
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2028

Study Registration Dates

• First Submitted: April 11, 2025
• First Submitted That Met QC Criteria: April 29, 2025
• First Posted (Actual): May 2, 2025

Study Record Updates

• Last Update Posted (Estimated): October 29, 2025
• Last Update Submitted That Met QC Criteria: October 27, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: 23860 (Other Identifier: City of Hope Medical Center); P30CA033572 (U.S. NIH Grant/Contract); NCI-2025-02185 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No