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

Estrogen Receptor Positive Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03391388
• Other study ID #: MC1532
• Secondary ID: NCI-2017-02363MC
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 16, 2015
• Est. completion date: August 20, 2023

Study information

• Verified date: September 2022
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 168
• Est. completion date: August 20, 2023
• Est. primary completion date: June 20, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Carcinoma In Situ
• Breast Neoplasms
• Carcinoma
• Carcinoma in Situ
• Carcinoma, Ductal, Breast
• Carcinoma, Intraductal, Noninfiltrating
• Carcinoma, Lobular
• 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

Intervention

Radiation:
• 3-Dimensional Conformal Accelerated Partial Breast Irradiation
Undergo 3D-CRT, catheter-based brachytherapy, or proton APBI

Procedure:
• Interstitial Radiation Therapy
Undergo catheter-based brachytherapy APBI

Other:
• Laboratory Biomarker Analysis
Correlative studies

Radiation:
• Photon Beam Radiation Therapy
Undergo 3D-CRT APBI
• Proton Beam Radiation Therapy
Undergo proton APBI

Other:
• Quality-of-Life Assessment
Ancillary studies

Locations

Country	Name	City	State
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	At 3 years
Secondary	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.	Up to 5 years
Secondary	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.	Up to 90 days post-radiation therapy (RT)
Secondary	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.	Up to 3 years post-RT
Secondary	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.	From study registration until the occurrence of one of the events in a composite endpoint, assessed up to 5 years
Secondary	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.	At 3 years
Secondary	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.	From registration to death due to any cause, assessed up to 5 years
Secondary	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.	Up to 5 years
Secondary	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.	At 3 years
Secondary	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.	Up to 5 years
Secondary	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.	Up to 5 years