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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03391388
Recruitment Status : Active, not recruiting
First Posted : January 5, 2018
Last Update Posted : June 5, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Tracking Information
First Submitted Date  ICMJE December 29, 2017
First Posted Date  ICMJE January 5, 2018
Last Update Posted Date June 5, 2019
Actual Study Start Date  ICMJE June 16, 2015
Estimated Primary Completion Date August 20, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 29, 2017)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03391388 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 29, 2017)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 3D-CRT, Proton, or Brachytherapy APBI in Treating Patients With Invasive and Non-invasive Breast Cancer
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • 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  ICMJE
  • 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
  • Radiation: Photon Beam Radiation Therapy
    Undergo 3D-CRT APBI
  • Radiation: Proton Beam Radiation Therapy
    Undergo proton APBI
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other Name: Quality of Life Assessment
Study Arms  ICMJE
  • Experimental: Cohort I (3D-CRT APBI)
    Patients undergo 3D-CRT APBI for 3-5 days.
    Interventions:
    • Radiation: 3-Dimensional Conformal Accelerated Partial Breast Irradiation
    • Other: Laboratory Biomarker Analysis
    • Radiation: Photon Beam Radiation Therapy
    • Other: Quality-of-Life Assessment
  • Experimental: Cohort II (proton APBI)
    Patients undergo proton beam radiation therapy APBI for 3-5 days.
    Interventions:
    • Radiation: 3-Dimensional Conformal Accelerated Partial Breast Irradiation
    • Other: Laboratory Biomarker Analysis
    • Radiation: Proton Beam Radiation Therapy
    • Other: Quality-of-Life Assessment
  • Experimental: Cohort III (brachytherapy APBI)
    Patients undergo brachytherapy ABPI for 3-5 days.
    Interventions:
    • Radiation: 3-Dimensional Conformal Accelerated Partial Breast Irradiation
    • Procedure: Interstitial Radiation Therapy
    • Other: Laboratory Biomarker Analysis
    • Other: Quality-of-Life Assessment
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: December 29, 2017)
168
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 20, 2020
Estimated Primary Completion Date August 20, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 50 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03391388
Other Study ID Numbers  ICMJE MC1532
NCI-2017-02363 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1532 ( Other Identifier: Mayo Clinic )
P30CA015083 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Robert Mutter Mayo Clinic
PRS Account Mayo Clinic
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP