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

• ClinicalTrials.gov Identifier: NCT03391388
• Recruitment Status: Active, not recruiting
• First Posted: January 5, 2018
• Last Update Posted: November 3, 2020
• Sponsor: Mayo Clinic
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Mayo Clinic

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.

Condition or disease	Intervention/treatment	Phase
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	Radiation: 3-Dimensional Conformal Accelerated Partial Breast Irradiation; Procedure: Interstitial Radiation Therapy; Other: Laboratory Biomarker Analysis; Radiation: Photon Beam Radiation Therapy; Radiation: Proton Beam Radiation Therapy; Other: Quality-of-Life Assessment	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 168 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: June 16, 2015
• Estimated Primary Completion Date: June 15, 2021
• Estimated Study Completion Date: August 20, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort I (3D-CRT APBI); Patients undergo 3D-CRT APBI for 3-5 days.	Radiation: 3-Dimensional Conformal Accelerated Partial Breast Irradiation; Undergo 3D-CRT, catheter-based brachytherapy, or proton APBI; Other Name: 3D Conformal Accelerated Partial Breast Irradiation; Other: Laboratory Biomarker Analysis; Correlative studies; Radiation: Photon Beam Radiation Therapy; Undergo 3D-CRT APBI; Other: Quality-of-Life Assessment; Ancillary studies; Other Name: Quality of Life Assessment
Experimental: Cohort II (proton APBI); Patients undergo proton beam radiation therapy APBI for 3-5 days.	Radiation: 3-Dimensional Conformal Accelerated Partial Breast Irradiation; Undergo 3D-CRT, catheter-based brachytherapy, or proton APBI; Other Name: 3D Conformal Accelerated Partial Breast Irradiation; Other: Laboratory Biomarker Analysis; Correlative studies; Radiation: Proton Beam Radiation Therapy; Undergo proton APBI; Other: Quality-of-Life Assessment; Ancillary studies; Other Name: Quality of Life Assessment
Experimental: Cohort III (brachytherapy APBI); Patients undergo brachytherapy ABPI for 3-5 days.	Radiation: 3-Dimensional Conformal Accelerated Partial Breast Irradiation; Undergo 3D-CRT, catheter-based brachytherapy, or proton APBI; Other Name: 3D Conformal Accelerated Partial Breast Irradiation; Procedure: Interstitial Radiation Therapy; Undergo catheter-based brachytherapy APBI; Other Names: BRACHYTHERAPY, INTERSTITIAL; implant radiation; Other: Laboratory Biomarker Analysis; Correlative studies; Other: Quality-of-Life Assessment; Ancillary studies; Other Name: Quality of Life Assessment

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.

Eligibility Criteria

• Ages Eligible for Study: 50 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Arizona

Mayo Clinic Hospital

Phoenix, Arizona, United States, 85054

United States, Florida

Mayo Clinic in Florida

Jacksonville, Florida, United States, 32224-9980

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Robert Mutter; Mayo Clinic

More Information

• Responsible Party: Mayo Clinic
• ClinicalTrials.gov Identifier: NCT03391388
• Other Study ID Numbers: MC1532; NCI-2017-02363 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); MC1532 ( Other Identifier: Mayo Clinic ); P30CA015083 ( U.S. NIH Grant/Contract )
• First Posted: January 5, 2018
• Last Update Posted: November 3, 2020
• Last Verified: November 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal, Breast; Breast Carcinoma In Situ; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Lobular; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Breast Diseases; Skin Diseases; Carcinoma, Ductal; Adenocarcinoma; Neoplasms, Ductal, Lobular, and Medullary