Shave Margins in Breast Conservation Therapy (SMART)

Shave Margins in Breast Conservation Therapy (SMART): A Randomized Controlled Trial

The investigators propose a randomized controlled superiority trial of standard breast-conserving surgery (BCS) versus BCS with cavity shave margins (CSM). The main objectives of this trial will be to evaluate prospectively the impact of routine standardized CSM on margin status following primary surgery for early stage breast cancer (Stage 0 - II), on post-operative patient satisfaction and cosmetic outcomes, and on general intraoperative time and operative costs. A parallel group format will be implemented to compare this modified surgical therapy - BCS with CSM - with BCS alone, which is the current standard of care.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer; Cancer of Breast; Cancer of the Breast
• Intervention / Treatment: Procedure: Breast-conserving surgery (BCS); Behavioral: BREAST-Q Questionnaire; Device: 3-D breast imaging; Other: Indocyanine green; Device: Intraoperative imaging device; Procedure: Peripheral blood draw; Procedure: Cavity shave margins (CSM)

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Newly diagnosed, biopsy-proven stage 0-II breast cancer.
• Planning to undergo breast-conserving surgery.
• At least 18 years of age and no more than 85 years of age.
• Female.
• Able to understand and willing to sign an IRB-approved written informed consent document.

Exclusion Criteria:

• Prior surgical treatment for this diagnosis.
• Undergone neoadjuvant chemotherapy.
• History of prior chest radiation therapy.
• Known metastatic disease.
• Pregnant.
• Preference for mastectomy instead of breast-conserving surgery.
• History of ipsilateral breast cancer.
• Goggle assessment substudy: Iodine or seafood allergies.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: BCS Arm (breast-conserving surgery - standard of care); Defined as partial mastectomy, lumpectomy, or local excisional biopsy with or without needle/wire localization; The ICG will be prepared per manufacturer instructions and diluted to allow for intravenous dosing up to 0.5 mg/kg (except for those patients with iodine or seafood allergies or in cases where the goggles are unavailable for use).; Following the BCS procedures, the surgeon or a study team member will don the goggles and state the NIR fluorescence margin information of the excised primary tumor specimen and of and CSM that are taken.	Procedure: Breast-conserving surgery (BCS); Behavioral: BREAST-Q Questionnaire; Device: 3-D breast imaging; Using a 3-D breast imaging camera Vectra 3-D XT; Other: Indocyanine green; Other Names: ICG; Device: Intraoperative imaging device; The goggle device is wearable, compact, and battery-operated, and it allows for hands-free operation by the wearer. The goggles provide functional information via a NIR light-emitting diode (LED) integrated within one of the eyepieces, which causes NIR fluorescence excitation of the molecular probes within the surgical field; Procedure: Peripheral blood draw; -Time of surgery if coordinator is available
Experimental: CSM Arm (breast-conserving surgery with cavity shave margins); Partial mastectomy, lumpectomy, or local excisional biopsy with or without needle/wire localization with the addition of additional tissue specimens from all 6 margins (anterior, posterior, superior, inferior, medial, lateral) of the wound cavity if possible. In cases where an additional margin would involve the skin at the anterior margin and/or the pectoral muscle at the posterior margin, only the 4 (or 5) remaining margins should be obtained; A margin thickness of 1 cm will be the defined goal to establish uniformity among different surgeons and allow for appropriate pathological evaluation; The ICG will be prepared per manufacturer instructions and diluted to allow for intravenous dosing up to 0.5 mg/kg (no iodine or seafood allergies).; Following the BCS procedures, the surgeon or a study team member will don the goggles and state the NIR fluorescence margin information of the excised primary tumor specimen and of any CSM that are taken.	Procedure: Breast-conserving surgery (BCS); Behavioral: BREAST-Q Questionnaire; Device: 3-D breast imaging; Using a 3-D breast imaging camera Vectra 3-D XT; Other: Indocyanine green; Other Names: ICG; Device: Intraoperative imaging device; The goggle device is wearable, compact, and battery-operated, and it allows for hands-free operation by the wearer. The goggles provide functional information via a NIR light-emitting diode (LED) integrated within one of the eyepieces, which causes NIR fluorescence excitation of the molecular probes within the surgical field; Procedure: Peripheral blood draw; -Time of surgery if coordinator is available; Procedure: Cavity shave margins (CSM)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with positive margins on pathological specimen analysis		Completion of surgery for all enrolled patients (approximately 60 months)
Patient perceptions of the surgery as measured by BREAST-Q questionnaire and novel 3-dimensional breast imaging	The BREAST-Q questionnaire consists of 13 sections.; The sections ask the patient questions about how they feel about how their breast area looks, how they feel emotionally, any physical side effects, and sexual side effects.; Some of the sections ask the patients to answer a question on a scale of None of the Time (equals=1) to All of the Time (equals=5); Some of the sections ask the patients to answer a question on a scale of Very Dissatisfied (equals=1) to Very Satisfied (equals=4)	6-12 months post-surgery or post-radiation therapy, whichever is later)
Compare intraoperative NIR fluorescence from goggle system with pathologic tissue exam results		Completion of surgery for all enrolled patients (approximately 60 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relationship between CSM and volume of tissue excised in association iwth post-operative aesthetic outcomes		6-12 months post-surgery or post-radiation therapy, whichever is later)
Cost-effectiveness of routine CSM in BCS as measured by operative time, specimen processing, and resource usage		Completion of surgery for all enrolled patients (approximately 60 months)
Disease status associated with cancer biomarkers	The investigators plan to assess plasma and serum levels of several candidate biomarkers, including a phosphorylated form of the annexin A2 protein ("P-annexin A2"), in study patients by immunoblotting/ELISA. This biomarker evaluation in the context of disease status will provide new information in the clinical detection and diagnosis of malignancy. Successful validation of these biomarkers may lead to development of novel blood-based cancer diagnostic tests.	Completion of surgery for all enrolled patients (approximately 60 months)
Tumor characteristics associated with cancer biomarkers	The investigators plan to assess plasma and serum levels of several candidate biomarkers, including a phosphorylated form of the annexin A2 protein ("P-annexin A2"), in study patients by immunoblotting/ELISA. This biomarker evaluation in the context of tumor characteristics will provide new information in the clinical detection and diagnosis of malignancy. Successful validation of these biomarkers may lead to development of novel blood-based cancer diagnostic tests.	Completion of surgery for all enrolled patients (approximately 60 months)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Julie Margenthaler, M.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2016
• Primary Completion (Actual): November 27, 2019
• Study Completion (Actual): November 27, 2019

Study Registration Dates

• First Submitted: June 1, 2015
• First Submitted That Met QC Criteria: June 2, 2015
• First Posted (Estimate): June 3, 2015

Study Record Updates

• Last Update Posted (Actual): June 25, 2020
• Last Update Submitted That Met QC Criteria: June 22, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 201506053

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No