3D-CRT, Proton, or Brachytherapy APBI in Treating Patients With Invasive and Non-invasive Breast Cancer

January 4, 2023 updated by: Mayo Clinic

A Phase II Study of Accelerated 3 Fraction Photon and Proton Partial Breast External Beam Radiotherapy and Partial Breast Brachytherapy for Early Invasive and Noninvasive Breast Cancer

This phase II trial studies the side effects of three-dimensional conformal external-beam photon radiotherapy (3D-CRT), proton, or brachytherapy accelerated partial breast irradiation (APBI) in treating patients with breast cancer that has or hasn't spread from where it began in the breast to surrounding normal tissue. Radiation therapy such as photon and proton partial breast external beam radiotherapy, uses high energy x-rays to kill tumor cells and shrink tumors. Giving radiation therapy in different ways may kill more tumor cells. Brachytherapy, also known as internal radiation therapy, uses radioactive material placed directly into or near a tumor to kill tumor cells. It is not yet known whether photon or proton partial breast external beam radiotherapy or partial breast brachytherapy works better in treating patients with breast cancer.

Study Overview

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the rate of adverse cosmesis (defined as fair or poor cosmesis) with accelerated 3 fraction APBI at 3 years, compared to baseline.

SECONDARY OBJECTIVES:

I. To evaluate the acute and late toxicities of accelerated 3 fraction APBI. II. To evaluate local disease control of accelerated 3 fraction APBI. III. To assess the rate of patient reported adverse cosmesis at 2 years, compared to baseline.

IV. To assess quality of life and other patient reported outcomes following accelerated 3 fraction APBI.

V. To compare the local control, acute and late toxicities, cosmesis, quality of life and other patient reported outcomes between the three radiation therapy techniques (3D-CRT, proton, brachytherapy).

VI. To evaluate clinical features, dose-volume parameters, and genetic variants associated with fair and poor cosmetic outcome.

OUTLINE: Patients are assigned to 1 of 3 cohorts.

COHORT I: Patients undergo 3D-CRT APBI for 3-5 days.

COHORT II: Patients undergo proton beam radiation therapy APBI for 3-5 days.

COHORT III: Patients undergo brachytherapy ABPI for 3-5 days.

After completion of study treatment, patients are followed up at 12 weeks, 12 months, and annually for 5 years.

Study Type

Interventional

Enrollment (Anticipated)

168

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic Hospital
    • Florida
      • Jacksonville, Florida, United States, 32224-9980
        • Mayo Clinic in Florida
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Grade 1-3 invasive ductal, mammary, mucinous, tubular, colloidal, or pure ductal carcinoma in situ (DCIS) measuring =< 2.5 cm on final pathology (the tumor should be clinical stage T1N0M0 in patients electing brachytherapy in whom the catheter will be placed intraoperatively)
  • Estrogen receptor (ER)+ (ER- DCIS meeting other eligibility criteria are eligible)
  • Unicentric: patients with microscopic multifocality are eligible as long as the total pathologic tumor size is =< 2.5 cm
  • Surgical treatment of the breast must have been lumpectomy
  • The final margins of the resected specimen must be histologically free of tumor
  • Patients with DCIS do not require an axillary staging procedure; for patients with invasive breast cancer (except T1mi), an axillary staging procedure should be performed (either sentinel lymph node biopsy alone or axillary dissection and the axillary node must be pathologically negative) and they should be pathologically node negative; Note: Patients with N0 (i+) tumors on sentinel lymph node mapping or dissection (i.e., if the tumor deposit is 0.2 mm or less as determined by immunohistochemistry or hematoxylin and eosin staining) will also be eligible
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
  • Ability to complete questionnaire(s) by themselves or with assistance
  • Ability to elect radiotherapy care in conjunction with their physician
  • Able and willing to provide written informed consent
  • Willingness to return to enrolling institution for follow-up (during the active monitoring phase of the study)
  • Willing to provide tissue and blood samples for correlative research purposes
  • Rochester and Arizona patients: Willing to sign consent onto the Mayo Clinic Radiotherapy Patient Outcomes Registry and Biobanking study and collect involved blood specimen prior to the start of radiation therapy, IRB number 15-000136.

Exclusion Criteria:

  • Any of the following because this study involves therapy that has known genotoxic, mutagenic and teratogenic effects:

    • Pregnant women
    • Nursing women
    • Women of childbearing potential who are unwilling to employ adequate contraception
  • Neoadjuvant chemotherapy
  • Prior history of ipsilateral breast cancer
  • Prior radiation therapy to the ipsilateral breast or thorax
  • 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
  • Active collagen-vascular disease that, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
  • Paget?s disease of the breast
  • Proven multicentric carcinoma (DCIS or invasive) in more than one quadrant or separated by 4 or more centimeters or diffuse (> 1 quadrant) suspicious calcifications
  • Histologic evidence of angiolymphatic invasion (ALI); Note: Cases termed focally suspicious for ALI but where no definitive ALI is found are eligible
  • Surgical margins that cannot be microscopically assessed or that are positive
  • Pathologic tumor > 2.5 cm in size
  • Metastatic disease
  • Patients for whom the delivery of APBI is not feasible or any of the dosimetric treatment criteria have not been met
  • BRCA 1/2 mutation; Note: Patients are not required to undergo BRCA1 and BRCA2 or other genetic mutation tests in order to enroll on the study. However, in the event a patient is tested and is found to be a mutation carrier, she would be excluded from the study
  • Breast implants (patients who have had implants removed are eligible)
  • Extensive intraductal component
  • Active connective tissue disease
  • Reduction mammoplasty if 3DCRT or proton APBI are planned
  • Last surgery > 10 weeks from enrollment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort I (3D-CRT APBI)
Patients undergo 3D-CRT APBI for 3-5 days.
Correlative studies
Ancillary studies
Other Names:
  • Quality of Life Assessment
Undergo 3D-CRT, catheter-based brachytherapy, or proton APBI
Other Names:
  • 3D Conformal Accelerated Partial Breast Irradiation
Undergo 3D-CRT APBI
Experimental: Cohort II (proton APBI)
Patients undergo proton beam radiation therapy APBI for 3-5 days.
Correlative studies
Ancillary studies
Other Names:
  • Quality of Life Assessment
Undergo 3D-CRT, catheter-based brachytherapy, or proton APBI
Other Names:
  • 3D Conformal Accelerated Partial Breast Irradiation
Undergo proton APBI
Experimental: Cohort III (brachytherapy APBI)
Patients undergo brachytherapy ABPI for 3-5 days.
Correlative studies
Ancillary studies
Other Names:
  • Quality of Life Assessment
Undergo 3D-CRT, catheter-based brachytherapy, or proton APBI
Other Names:
  • 3D Conformal Accelerated Partial Breast Irradiation
Undergo catheter-based brachytherapy APBI
Other Names:
  • BRACHYTHERAPY, INTERSTITIAL
  • implant radiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage difference in patients with adverse cosmesis (fair or poor cosmesis)
Time Frame: At 3 years
The percentage difference in patients with adverse cosmesis will be estimated using a binomial estimator (number of women who had an adverse cosmesis event at 3 years minus number of women who had an adverse cosmesis event at baseline, and then divided by total number of women in the primary analysis) and a 95% exact binomial confidence interval.
At 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Distant recurrence
Time Frame: Up to 5 years
The distant breast cancer recurrence cumulative incidence will be estimated using a competing risks method (Gooley et al.). The competing risks will be local/regional breast cancer recurrence and death.
Up to 5 years
Incidence of acute adverse events (AEs)
Time Frame: Up to 90 days post-radiation therapy (RT)
The maximum grade for each type of acute AE will be recorded for each patient. Data will be summarized as frequencies and relative frequencies.
Up to 90 days post-radiation therapy (RT)
Incidence of late adverse events
Time Frame: Up to 3 years post-RT
The maximum grade for each type of acute AE will be recorded for each patient. Data will be summarized as frequencies and relative frequencies.
Up to 3 years post-RT
Invasive disease free survival
Time Frame: From study registration until the occurrence of one of the events in a composite endpoint, assessed up to 5 years
This endpoint includes invasive IBTR, regional invasive breast cancer recurrence, distant breast cancer recurrence, death due to any cause, contralateral invasive breast cancer, and second primary non-breast invasive disease. The DFS will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% confidence interval (CI)s.
From study registration until the occurrence of one of the events in a composite endpoint, assessed up to 5 years
Ipsilateral breast tumor recurrence (IBTR)
Time Frame: At 3 years
IBTR is defined as both invasive and non-invasive breast cancer involving the same breast parenchyma as the original tumor. Will be estimated using a competing risks method (Gooley et al.). The competing risks will be regional/distant breast cancer recurrence and death.
At 3 years
Overall survival
Time Frame: From registration to death due to any cause, assessed up to 5 years
This endpoint includes invasive IBTR, regional invasive breast cancer recurrence, distant breast cancer recurrence, death due to any cause, contralateral invasive breast cancer, and second primary non-breast invasive disease. 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
Panel-assessed cosmetic outcome
Time Frame: Up to 5 years
Will be assessed by a panel of breast cancer medical providers using digital photographs. The values of the cosmesis instruments (patient self-reported and panel-assessed) will be summarized with the frequencies of fair or poor cosmesis events at baseline and 3 years, and the difference at 3 years, as well as their relative exact binomial confidence intervals.
Up to 5 years
Patient self-reported cosmetic outcomes assessed using a modified Harvard Cosmesis Scale in the Breast Cancer Treatment Outcome Scale (BCTOS)
Time Frame: At 3 years
The values of the cosmesis instruments (patient self-reported and panel-assessed) will be summarized with the frequencies of fair or poor cosmesis events at baseline and 3 years, and the difference at 3 years, as well as their relative exact binomial confidence intervals.
At 3 years
Quality of life (QOL) assessed by Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Time Frame: Up to 5 years
The QOL measurements will be summarized at each time point as mean +/- standard deviation (SD) and median (minimum value, maximum value). Changes in the QOL measurements from baseline will be determined at each follow-up measurement. These will be displayed as spaghetti plots. The assessment of the changes at each time point will be done with a paired t-test or Wilcoxon signed rank test, whichever is appropriate.
Up to 5 years
Regional recurrence
Time Frame: Up to 5 years
The regional breast cancer recurrence cumulative incidence will be estimated using a competing risks method (Gooley et al.). The competing risks will be local/distant breast cancer recurrence and death.
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Robert Mutter, Mayo Clinic

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 16, 2015

Primary Completion (Actual)

June 20, 2020

Study Completion (Anticipated)

August 20, 2023

Study Registration Dates

First Submitted

December 29, 2017

First Submitted That Met QC Criteria

December 29, 2017

First Posted (Actual)

January 5, 2018

Study Record Updates

Last Update Posted (Actual)

January 5, 2023

Last Update Submitted That Met QC Criteria

January 4, 2023

Last Verified

September 1, 2022

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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