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

Phase 3

Completed

Conditions: Stage II Breast Cancer AJCC v6 and v7
Stage IIIA Breast Cancer AJCC v7
Stage IB Breast Cancer AJCC v7
Stage IIA Breast Cancer AJCC v6 and v7
Stage I Breast Cancer AJCC v7
Stage IA Breast Cancer AJCC v7
Stage IIB Breast Cancer AJCC v6 and v7

Interventions: Other: Quality-of-Life Assessment
Radiation: Hypofractionated Radiation Therapy
Radiation: Radiation Therapy

Registration Number: NCT03324802

Lead Sponsor: Mayo Clinic

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 107

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (radiation therapy, 15 fractions)	Quality-of-Life Assessment	Within 12 weeks of breast cancer surgery or adjuvant chemotherapy, patients undergo standard radiation therapy in 15 daily fractions for 10 days.
Arm 2 (hypofractionated radiation therapy, 5 fractions)	Quality-of-Life Assessment	Within 12 weeks of breast cancer surgery or adjuvant chemotherapy, patients undergo hypofractionated radiation therapy in 5 daily fractions for 5 days.
Arm 2 (hypofractionated radiation therapy, 5 fractions)	Hypofractionated Radiation Therapy	Within 12 weeks of breast cancer surgery or adjuvant chemotherapy, patients undergo hypofractionated radiation therapy in 5 daily fractions for 5 days.
Arm I (radiation therapy, 15 fractions)	Radiation Therapy	Within 12 weeks of breast cancer surgery or adjuvant chemotherapy, patients undergo standard radiation therapy in 15 daily fractions for 10 days.

Primary Outcome Measures

Name	Time	Method
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	24 months	The complication rate will be reported by arm.

Secondary Outcome Measures

Name	Time	Method
Number of Patients Experiencing Acute (Grade 3+) Adverse Events (AEs)	3 months	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.
Number of Patients Experiencing Grade 3+ Late Adverse Events	24 months	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.
Percent of Patients With Locoregional Recurrence	5 years	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.
Number of Patients Experiencing Distant Recurrence	5 years	Distant recurrence defined as metastatic cancer that has either been biopsy confirmed or clinically diagnosed as recurrent invasive breast cancer
Invasive Disease-free	5 years	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.
Cause-specific Survival	1 year	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.
Overall Survival	1 year	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.
Disease-Free Survival	5 years	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.

Trial Locations

Locations (3): Mayo Clinic Florida
🇺🇸
Jacksonville, Florida, United States
Mayo Clinic in Arizona
🇺🇸
Scottsdale, Arizona, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States