Anatomic Stage IA Breast Cancer AJCC v8, Anatomic Stage IB Breast Cancer AJCC v8, Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8, Prognostic Stage IA Breast Cancer AJCC v8, Prognostic Stage IB Breast Cancer AJCC v8, Prognostic Stage I Breast Cancer AJCC v8, Prognostic Stage IIA Breast Cancer AJCC v8
Conditions
Brief summary
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.
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.
Interventions
RADIATIONHypofractionated Radiation Therapy
Undergo hypofractionated radiation therapy
Sponsors
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response (pCR) Rate Defined as a Residual Tumor Burden of 0-1 in the Surgical Specimen | up to 2 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Acute Adverse Events (AE) | Up to 180 days post radiation therapy | 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. |
| Incidence of Late Adverse Events | Up to 5 years post radiation therapy | 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. |
| Locoregional Control | Up to 5 years | 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. |
| Invasive Disease-free Survival | From registration until the time of disease recurrence or death due to any cause, assessed up to 5 years | Will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% confidence intervals (CIs). |
| Distant Recurrence | Up to 5 years | — |
| Disease- Free Survival | From registration until the time of disease recurrence or death due to any cause, assessed up to 5 years | Will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% CIs. |
| Cause-specific Survival | From registration to death due to breast cancer assessed up to 5 years | Will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% CIs. |
| Overall Survival | From registration to death due to any cause assessed up to 5 years | Will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% CIs. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORCarlos E. Vargas, M.D.
Mayo Clinic
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.\>\>
\>\> Hypofractionated Radiation Therapy: Undergo hypofractionated radiation therapy | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Treatment (Hypofractionated Radiation Therapy) |
|---|---|
| Age, Continuous | 63.9 years STANDARD_DEVIATION 8.4 |
| Enrollment Site Arizona | 16 Participants |
| Enrollment Site Florida | 8 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Method of Payment Medicare | 9 Participants |
| Method of Payment Private Insurance | 15 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 21 Participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 24 |
| other Total, other adverse events | 22 / 24 |
| serious Total, serious adverse events | 2 / 24 |
Outcome results
Primary
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.
Time frame: up to 2 years
Population: If more than the target number of 22 patients are accrued, the additional patients will not be used to evaluate the stopping rule or used in any decision making process.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (hypofractionated radiation therapy) | Pathologic Complete Response (pCR) Rate Defined as a Residual Tumor Burden of 0-1 in the Surgical Specimen | 0.64 proportion of participants |
Secondary
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.
Time frame: From registration to death due to breast cancer assessed up to 5 years
Secondary
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.
Time frame: From registration until the time of disease recurrence or death due to any cause, assessed up to 5 years
Secondary
Distant Recurrence
Time frame: Up to 5 years
Secondary
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.
Time frame: Up to 5 years post radiation therapy
Secondary
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).
Time frame: From registration until the time of disease recurrence or death due to any cause, assessed up to 5 years
Secondary
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.
Time frame: Up to 5 years
Secondary
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.
Time frame: Up to 180 days post radiation therapy
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Treatment (hypofractionated radiation therapy) | Number of Participants With Acute Adverse Events (AE) | Any Grade 2+ AE | No | 16 Participants |
| Treatment (hypofractionated radiation therapy) | Number of Participants With Acute Adverse Events (AE) | Any Grade 2+ AE | Yes | 8 Participants |
| Treatment (hypofractionated radiation therapy) | Number of Participants With Acute Adverse Events (AE) | Any Grade 3+ AE | No | 19 Participants |
| Treatment (hypofractionated radiation therapy) | Number of Participants With Acute Adverse Events (AE) | Any Grade 3+ AE | Yes | 5 Participants |
Secondary
Overall Survival
Will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% CIs.
Time frame: From registration to death due to any cause assessed up to 5 years
Other Pre-specified
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.
Time frame: Up to 5 years
Other Pre-specified
Panel Assessed Cosmetic Outcome
Cosmesis will be assessed by a panel of breast cancer medical providers using digital photographs.
Time frame: Baseline up to 2 years
Other Pre-specified
Pathologic Changes Seen in Breast Cancer Patients With Preoperative Radiation
Will be described.
Time frame: Up to 5 years
Other Pre-specified
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.
Time frame: Baseline up to 5 years
Other Pre-specified
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.
Time frame: Up to 5 years
Other Pre-specified
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.
Time frame: Up to 5 years