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

Primary Purpose

Ductal Breast Carcinoma In Situ, Estrogen Receptor Positive, Grade 1 Invasive Breast Carcinoma

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
3-Dimensional Conformal Accelerated Partial Breast Irradiation
Interstitial Radiation Therapy
Laboratory Biomarker Analysis
Photon Beam Radiation Therapy
Proton Beam Radiation Therapy
Quality-of-Life Assessment
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ductal Breast Carcinoma In Situ

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic Hospital
  • Mayo Clinic in Florida
  • Mayo Clinic

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Cohort I (3D-CRT APBI)

Cohort II (proton APBI)

Cohort III (brachytherapy APBI)

Arm Description

Patients undergo 3D-CRT APBI for 3-5 days.

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

Patients undergo brachytherapy ABPI for 3-5 days.

Outcomes

Primary Outcome Measures

Percentage difference in patients with adverse cosmesis (fair or poor cosmesis)
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.

Secondary Outcome Measures

Distant recurrence
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.
Incidence of acute adverse events (AEs)
The maximum grade for each type of acute AE will be recorded for each patient. Data will be summarized as frequencies and relative frequencies.
Incidence of late adverse events
The maximum grade for each type of acute AE will be recorded for each patient. Data will be summarized as frequencies and relative frequencies.
Invasive disease free survival
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.
Ipsilateral breast tumor recurrence (IBTR)
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.
Overall survival
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.
Panel-assessed cosmetic outcome
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.
Patient self-reported cosmetic outcomes assessed using a modified Harvard Cosmesis Scale in the Breast Cancer Treatment Outcome Scale (BCTOS)
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.
Quality of life (QOL) assessed by Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
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.
Regional recurrence
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.

Full Information

First Posted
December 29, 2017
Last Updated
January 4, 2023
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT03391388
Brief Title
3D-CRT, Proton, or Brachytherapy APBI in Treating Patients With Invasive and Non-invasive Breast Cancer
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 16, 2015 (Actual)
Primary Completion Date
June 20, 2020 (Actual)
Study Completion Date
August 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
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ductal Breast Carcinoma In Situ, Estrogen Receptor Positive, Grade 1 Invasive Breast Carcinoma, Grade 2 Invasive Breast Carcinoma, Grade 3 Invasive Breast Carcinoma, Invasive Ductal and Lobular Carcinoma In Situ, Mucinous Breast Carcinoma, Tubular Breast Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Non-Randomized
Enrollment
168 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort I (3D-CRT APBI)
Arm Type
Experimental
Arm Description
Patients undergo 3D-CRT APBI for 3-5 days.
Arm Title
Cohort II (proton APBI)
Arm Type
Experimental
Arm Description
Patients undergo proton beam radiation therapy APBI for 3-5 days.
Arm Title
Cohort III (brachytherapy APBI)
Arm Type
Experimental
Arm Description
Patients undergo brachytherapy ABPI for 3-5 days.
Intervention Type
Radiation
Intervention Name(s)
3-Dimensional Conformal Accelerated Partial Breast Irradiation
Other Intervention Name(s)
3D Conformal Accelerated Partial Breast Irradiation
Intervention Description
Undergo 3D-CRT, catheter-based brachytherapy, or proton APBI
Intervention Type
Procedure
Intervention Name(s)
Interstitial Radiation Therapy
Other Intervention Name(s)
BRACHYTHERAPY, INTERSTITIAL, implant radiation
Intervention Description
Undergo catheter-based brachytherapy APBI
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Radiation
Intervention Name(s)
Photon Beam Radiation Therapy
Intervention Description
Undergo 3D-CRT APBI
Intervention Type
Radiation
Intervention Name(s)
Proton Beam Radiation Therapy
Intervention Description
Undergo proton APBI
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Percentage difference in patients with adverse cosmesis (fair or poor cosmesis)
Description
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.
Time Frame
At 3 years
Secondary Outcome Measure Information:
Title
Distant recurrence
Description
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.
Time Frame
Up to 5 years
Title
Incidence of acute adverse events (AEs)
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.
Time Frame
Up to 90 days post-radiation therapy (RT)
Title
Incidence of late adverse events
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.
Time Frame
Up to 3 years post-RT
Title
Invasive disease free survival
Description
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.
Time Frame
From study registration until the occurrence of one of the events in a composite endpoint, assessed up to 5 years
Title
Ipsilateral breast tumor recurrence (IBTR)
Description
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.
Time Frame
At 3 years
Title
Overall survival
Description
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.
Time Frame
From registration to death due to any cause, assessed up to 5 years
Title
Panel-assessed cosmetic outcome
Description
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.
Time Frame
Up to 5 years
Title
Patient self-reported cosmetic outcomes assessed using a modified Harvard Cosmesis Scale in the Breast Cancer Treatment Outcome Scale (BCTOS)
Description
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.
Time Frame
At 3 years
Title
Quality of life (QOL) assessed by Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Description
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.
Time Frame
Up to 5 years
Title
Regional recurrence
Description
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.
Time Frame
Up to 5 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Mutter
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic Hospital
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
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

Learn more about this trial

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

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