Hypofractionated Radiation Therapy in Preventing Recurrence in Patients With Breast Cancer After Surgery

A Phase III Trial of Hypofractionated Radiotherapy to the Whole Breast Alone After Breast Conserving Surgery

This randomized phase III trial studies how well hypofractionated radiation therapy works in preventing the return of tumor cells in breast cancer patients following 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: Completed
• Conditions: Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage IIIA Breast Cancer AJCC v7
• Intervention / Treatment: Other: Quality-of-Life Assessment; Radiation: Hypofractionated Radiation Therapy; Radiation: Radiation Therapy

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the 24-month complication rate of 5 fraction whole radiotherapy +/- concurrent boost as compared to 15 fraction radiotherapy +/- sequential boost.

SECONDARY OBJECTIVES:

I. To evaluate acute and late toxicity. II. To estimate the 5-year locoregional control, invasive disease-free survival and overall survival.

TERTIARY OBJECTIVES:

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

III. To evaluate the costs and comparative effectiveness of treatment. IV. Compare the use of photon therapy with spot scanning proton therapy in two different hypo-fractionated whole breast schemas.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Within 12 weeks of breast cancer surgery or adjuvant chemotherapy, patients undergo radiation therapy in 15 daily fractions for 10 days.

ARM II: Within 12 weeks of breast cancer surgery or adjuvant chemotherapy, patients undergo hypofractionated radiation therapy in 5 daily fractions for 5 days.

After completion of study treatment, patients are followed up to 5 years.

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic 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
• Pathologic stage T0-T3N0-N1M0
• 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 12 weeks of last surgery (breast or axilla) or last chemotherapy (if applicable)
• Able to complete all mandatory tests
• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
• Fair, good or excellent cosmesis, as determined by trained nurse assessment using the Harvard Cosmetic Scale
• Radiotherapy must begin within 12 weeks of the last breast cancer surgery or the last dose of adjuvant chemotherapy
• Breast conserving 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
• Prior receipt of ipsilateral breast or chest wall radiation
• Positive margins on ink after definitive surgery either for ductal carcinoma in situ (DCIS) or invasive cancer
• History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior study entry
• Recurrent breast cancer
• Indications for comprehensive regional nodal irradiation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 2 (hypofractionated radiation therapy, 5 fractions); Within 12 weeks of breast cancer surgery or adjuvant chemotherapy, patients undergo hypofractionated radiation therapy in 5 daily fractions for 5 days.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Radiation: Hypofractionated Radiation Therapy; Undergo hypofractionated radiation therapy; Other Names: Hypofractionated Radiotherapy; hypofractionation
Experimental: Arm I (radiation therapy, 15 fractions); Within 12 weeks of breast cancer surgery or adjuvant chemotherapy, patients undergo standard radiation therapy in 15 daily fractions for 10 days.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Radiation: Radiation Therapy; hypofractionated radiation therapy; Other Names: Cancer Radiotherapy; Irradiate; Irradiated; Radiation; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; irradiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complication Rate, Defined as the Percentage of Women Who Develop Grade 3 or Higher Late Adverse Event and/or Deterioration of Cosmesis From Excellent/Good to Fair/Poor or From Fair to Poor	The complication rate will be reported by arm.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cause-specific Survival	Will be estimated with a Kaplan-Meier estimator and curve by treatment arm. Estimates will be given for one year with 95% CIs. Comparison between arms will employ a log-rank test.	1 year
Overall Survival	Will be estimated with a Kaplan-Meier estimator and curve by treatment arm. Estimates will be given for one year along with 95% CIs. Comparison between arms will employ a log-rank test.	1 year
Number of Patients Experiencing Distant Recurrence	Distant recurrence defined as metastatic cancer that has either been biopsy confirmed or clinically diagnosed as recurrent invasive breast cancer	5 years
Number of Patients Experiencing Acute (Grade 3+) Adverse Events (AEs)	The maximum grade for each type of acute (grade 3+) AE will be recorded for each patient. Data will be summarized as frequencies and relative frequencies by treatment arm. The relationship of the adverse event(s) to the study treatment will be taken into consideration. Number of patients experiencing one or more grade 3+ events will be compared between arms using chi-squared tests. Adverse events were assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	3 months
Number of Patients Experiencing Grade 3+ 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. The relationship of the adverse event(s) to the study treatment will be taken into consideration. Number of patients experiencing one or more grade 3+ late AEs will be compared between arms using chi-squared tests.	24 months
Invasive Disease-free	Will be estimated with a Kaplan-Meier estimator and curve by treatment arm. Median invasive disease-free time will be given along with standard error. Comparison between arms will employ a log-rank test.	5 years
Percent of Patients With Locoregional Recurrence	The cumulative incidence of locoregional recurrence will be estimated using a competing risks method by treatment arm. The competing risks will be distant breast cancer recurrence and death. Comparison between arms will employ Fine-Gray regression. Locoregional recurrence is clinically diagnosed invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast at 5 years.	5 years
Disease-Free Survival	Will be estimated with a Kaplan-Meier estimator and curve by treatment arm. Median disease free survival time and standard error will be estimated. Comparison between arms will employ a log-rank test.	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Reported Outcomes/Quality of Life	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 +/- standard deviation and median (minimum value, maximum value). Mixed models will be used to estimate changes at fixed time points.	Up to 5 years
Patient Reported Outcomes/Quality of Life	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 +/- standard deviation and median (minimum value, maximum value). Mixed models will be used to compare outcomes between arms.	Up to 5 years
Patient Self-reported Cosmesis	Will evaluate fatigue, breast pain, arm function. 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 at baseline, 2 years, and 5 years by treatment arm. Comparisons between arms will employ chi-squared tests.	Baseline up to 5 years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2018
• Primary Completion (Actual): January 31, 2022
• Study Completion (Actual): August 28, 2023

Study Registration Dates

• First Submitted: October 20, 2017
• First Submitted That Met QC Criteria: October 24, 2017
• First Posted (Actual): October 30, 2017

Study Record Updates

• Last Update Posted (Estimated): May 2, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 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: MC1635 (Other Identifier: Mayo Clinic in Arizona); NCI-2017-01944 (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