Hypofractionated Radiation Therapy in Treating Participants With Breast Cancer Before Surgery

A Pilot/Phase II Trial of Hypofractionated Radiotherapy to the Whole Breast Alone Before Breast Conserving Surgery

This phase II trial studies how well hypofractionated radiation therapy works in treating participants with breast cancer before surgery. 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage IA Breast Cancer AJCC v8; Anatomic Stage IB Breast Cancer AJCC v8; Anatomic Stage IIA Breast Cancer AJCC v8; Prognostic Stage I Breast Cancer AJCC v8; Prognostic Stage IA Breast Cancer AJCC v8; Prognostic Stage IB Breast Cancer AJCC v8; Prognostic Stage IIA Breast Cancer AJCC v8
• Intervention / Treatment: Radiation: Hypofractionated Radiation Therapy

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the pathologic complete response (pCR) rate after hypofractionated radiotherapy to the whole breast alone, based on the postsurgical specimen.

SECONDARY OBJECTIVES:

I. To evaluate acute and late toxicity with preoperative radiation including grade >= 2 pneumonitis.

II. To estimate the 5-year locoregional control, distant recurrence, invasive disease-free survival, cause-specific survival, and overall survival.

CORRELATIVE AND EXPLORATORY OBJECTIVES:

I. To evaluate patient-reported outcomes. II. To evaluate clinical features, treatment technique, dose-volume parameters, histologic and genetic variants associated with adverse events, and fair and poor cosmetic outcomes or unplanned surgical intervention.

III. Evaluate tumor mutation signatures before and after radiation; correlate tumor mutation signatures before and after radiation with pathologic information at the time of surgery.

IV. To describe the pathologic changes seen in breast cancer patients with preoperative radiation.

OUTLINE:

Participants undergo hypofractionated radiation therapy daily for 5 days, then undergo standard of care surgery 4-16 weeks after radiation therapy.

After completion of study treatment, participants are followed up at 12 weeks, 6, 12, 24, and 36 months, and 5 years after radiation therapy.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histological confirmation of breast cancer
• Clinical stage T0-T2 N0 M0
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2
• Able to and provides Institutional Review Board (IRB) approved study specific written informed consent
• Study entry must be within 120 days of last biopsy (breast)
• Able to complete all mandatory tests
• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
• Planned breast surgery and indications for whole breast radiotherapy

Exclusion Criteria:

• Medical contraindication to receipt of radiotherapy
• Severe active co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or providing informed consent
• Active systemic lupus or scleroderma
• Pregnancy
• Women of childbearing potential who are unwilling to employ adequate contraception
• Prior receipt of ipsilateral breast or chest wall radiation
• Recurrent breast cancer
• Indications for comprehensive regional nodal irradiation
• No neo-adjuvant therapy

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 (hypofractionated radiation therapy); Participants undergo hypofractionated radiation therapy daily for 5 days, then undergo standard of care surgery 4-16 weeks after radiation therapy.	Radiation: Hypofractionated Radiation Therapy; Undergo hypofractionated radiation therapy; Other Names: Hypofractionated Radiotherapy; hypofractionation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic Complete Response (pCR) Rate Defined as a Residual Tumor Burden of 0-1 in the Surgical Specimen	The proportion of successes (number of patients achieving pCR at time of definitive surgery) will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Acute Adverse Events (AE)	The maximum grade for each type of acute AE will be recorded for each patient. Data will be summarized as frequencies and relative frequencies. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.	Up to 180 days post radiation therapy
Incidence of Late Adverse Events	The maximum grade for each type of late AE will be recorded for each patient. Data will be summarized as frequencies and relative frequencies by treatment arm. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.	Up to 5 years post radiation therapy
Locoregional Control	The cumulative incidence of locoregional recurrence will be estimated using a competing risks method (Gooley et al.). The competing risks will be distant breast cancer recurrence and death.	Up to 5 years
Invasive Disease-free Survival	Will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% confidence intervals (CIs).	From registration until the time of disease recurrence or death due to any cause, assessed up to 5 years
Distant Recurrence		Up to 5 years
Disease- Free Survival	Will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% CIs.	From registration until the time of disease recurrence or death due to any cause, assessed up to 5 years
Cause-specific Survival	Will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% CIs.	From registration to death due to breast cancer assessed up to 5 years
Overall Survival	Will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% CIs.	From registration to death due to any cause assessed up to 5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Self-reporting of Toxicities	The subscales of the Breast Cancer Treatment Outcomes Scale (BCTOS), elements from Patient Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), and other patient reported measures such as fatigue, breast pain, breast shape, and arm related morbidity outlined in the appendix will be summarized as the mean +/- SD and median (minimum value, maximum value). Scale score trajectories over time will be examined using stream plots and mean plots with standard deviation error bars overall. Analysis will include percent change from baseline using t-tests and generalized linear models to test for changes at each time point and non-zero slope respectfully.	Up to 5 years
Patient Self-reported Cosmetic Outcomes	Assessed using a modified Harvard Cosmesis Scale and the BCTOS. The values of the cosmesis instruments (patient self-reported and panel-assessed) will be summarized with the frequencies and confidence intervals of fair or poor cosmesis events.	Baseline up to 5 years
Panel Assessed Cosmetic Outcome	Cosmesis will be assessed by a panel of breast cancer medical providers using digital photographs.	Baseline up to 2 years
Clinical Features, Treatment Technique, Dose-volume Parameters, Histologic and Genetic Variants	Associated with adverse events, and fair and poor cosmetic outcomes or unplanned surgical intervention.	Up to 5 years
Tumor Mutation Signatures	Will be analyzed before and after radiotherapy as compared to pathologic information at the time of surgery. Continuous variable will be compared using unpaired t tests and nominal variables will be compared using contingency tables and Chi square analyses.	Up to 5 years
Pathologic Changes Seen in Breast Cancer Patients With Preoperative Radiation	Will be described.	Up to 5 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Carlos E. Vargas, M.D., Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2018
• Primary Completion (Actual): June 30, 2021
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: August 6, 2018
• First Submitted That Met QC Criteria: August 6, 2018
• First Posted (Actual): August 10, 2018

Study Record Updates

• Last Update Posted (Actual): January 11, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: MC1732 (Other Identifier: Mayo Clinic in Arizona); NCI-2018-01606 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 17-004130 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No