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Hypofractionated Radiation Therapy in Treating Participants With Breast Cancer Before Surgery

Primary Purpose

Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage IA Breast Cancer AJCC v8, Anatomic Stage IB Breast Cancer AJCC v8

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Hypofractionated Radiation Therapy
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anatomic Stage I Breast Cancer AJCC v8

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic in Arizona
  • Mayo Clinic in Florida
  • Mayo Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (hypofractionated radiation therapy)

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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).
Distant Recurrence
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.
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.
Overall Survival
Will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% CIs.

Full Information

First Posted
August 6, 2018
Last Updated
January 5, 2023
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT03624478
Brief Title
Hypofractionated Radiation Therapy in Treating Participants With Breast Cancer Before Surgery
Official Title
A Pilot/Phase II Trial of Hypofractionated Radiotherapy to the Whole Breast Alone Before Breast Conserving Surgery
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 20, 2018 (Actual)
Primary Completion Date
June 30, 2021 (Actual)
Study Completion Date
November 20, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (hypofractionated radiation therapy)
Arm Type
Experimental
Arm Description
Participants undergo hypofractionated radiation therapy daily for 5 days, then undergo standard of care surgery 4-16 weeks after radiation therapy.
Intervention Type
Radiation
Intervention Name(s)
Hypofractionated Radiation Therapy
Other Intervention Name(s)
Hypofractionated Radiotherapy, hypofractionation
Intervention Description
Undergo hypofractionated radiation therapy
Primary Outcome Measure Information:
Title
Pathologic Complete Response (pCR) Rate Defined as a Residual Tumor Burden of 0-1 in the Surgical Specimen
Description
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
Secondary Outcome Measure Information:
Title
Number of Participants With Acute Adverse Events (AE)
Description
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
Title
Incidence of Late Adverse Events
Description
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
Title
Locoregional Control
Description
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
Title
Invasive Disease-free Survival
Description
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
Title
Distant Recurrence
Time Frame
Up to 5 years
Title
Disease- Free Survival
Description
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
Title
Cause-specific Survival
Description
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
Title
Overall Survival
Description
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 Outcome Measures:
Title
Patient Self-reporting of Toxicities
Description
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
Title
Patient Self-reported Cosmetic Outcomes
Description
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
Title
Panel Assessed Cosmetic Outcome
Description
Cosmesis will be assessed by a panel of breast cancer medical providers using digital photographs.
Time Frame
Baseline up to 2 years
Title
Clinical Features, Treatment Technique, Dose-volume Parameters, Histologic and Genetic Variants
Description
Associated with adverse events, and fair and poor cosmetic outcomes or unplanned surgical intervention.
Time Frame
Up to 5 years
Title
Tumor Mutation Signatures
Description
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
Title
Pathologic Changes Seen in Breast Cancer Patients With Preoperative Radiation
Description
Will be described.
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carlos Vargas
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Arizona
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
Mayo Clinic in Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224-9980
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

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Hypofractionated Radiation Therapy in Treating Participants With Breast Cancer Before Surgery

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