Pre-operative SABR With and Without Caloric Restriction for Early Stage Breast Cancer

SABR-CaRe: A Phase II Randomized Trial of Pre-Operative Stereotactic Ablative Radiation Therapy (SABR) With and Without Caloric Restriction for Early Stage Breast Cancer

This phase II trial studies the effect of calorie reduction while undergoing stereotactic ablative radiation therapy in treating patients with breast cancer. Stereotactic ablative radiation therapy (sABR) is a highly focused radiation treatment that gives an intense dose of radiation concentrated on a tumor, while limiting the dose to the surrounding organ. Giving SABR before surgery may make the tumor smaller. Adding dietary restrictions in combination with radiation therapy may help increase local control and decrease the spread of the cancer to other places in the body. The purpose of this trial is to identify if there is a decrease in tumor tissue in patients undergoing caloric restriction during pre-operative SABR, compared to patients undergoing pre-operative SABR alone.

Study Overview

• Status: Recruiting
• Conditions: Anatomic Stage 0 Breast Cancer AJCC v8; Invasive Breast Carcinoma; Breast Ductal Carcinoma in Situ; Triple Negative Breast Carcinoma; Anatomic Stage 1 Breast Cancer AJCC v8; Anatomic Stage 2 Breast Cancer AJCC v8; Anatomic Stage 3 Breast Cancer AJCC v8
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Procedure: Resection; Radiation: Stereotactic Body Radiation Therapy; Procedure: Sentinel Lymph Node Biopsy; Other: Best Practice; Other: Dietary Intervention; Procedure: Mammography; Procedure: Biospecimen Collection

Detailed Description

PRIMARY OBJECTIVE:

I. To detect a decrease in cellularity of the tumor in participants undergoing caloric restriction during pre-operative SABR as compared to participants undergoing SABR alone.

SECONDARY OBJECTIVES:

I. Change in miR-21 as defined by baseline and post radiation levels. II. Investigate measurable changes of patient and tumor characteristics from the combination of SABR and caloric restriction (CR) versus SABR alone to inform future trials.

III. To describe pathologic complete response (pCR) rates as defined by no residual carcinoma or no residual invasive carcinoma, but ductal carcinoma in situ (DCIS) may be present, in each arm as well as by subtype.

IV. To assess response of each treatment arm using contrast-enhanced mammography (CEM) and correlate with pathologic response.

V. To describe short term surgical outcomes including: sentinel lymph node (SLN) identification rate, positive margins requiring return to the operative room for re-excision, and post-operative complications (infection, delayed wound healing, seroma requiring aspiration).

VI. To measure patient reported health-related outcomes and satisfaction with outcome.

VII. To compare patient reported cosmesis to physician reported cosmesis scores, where cosmesis is rated as excellent, good, fair or poor.

VIII. To compare pCR rates between women randomized to SABR alone to women randomized to SABR + CR who are at least 80% adherent to the CR intervention.

IX. To compare pCR rates between women randomized to SABR alone who do not deviate by more than 10% from their baseline caloric intake to women randomized to SABR + CR who are at least 80% adherent to the CR intervention.

EXPLORATORY OBJECTIVES:

I. Tissue: To determine the downstream molecular effects of diet related to miR-21 such as FAS/FASL, PD-1, LAG3 and STAT3 expression.

II. Microbiome: Compare baseline to post-SABR microbiome species separately for each trial arm.

III. Serum: Determine if anti-tumor immunity has increased with increased CD8 and decreased Treg in tumor. Compare proteomic profiles.

TERTIARY OBJECTIVE:

I. To determine the ipsilateral breast recurrence rate, distant disease-free interval, recurrence free survival, and overall survival.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive standard dietary recommendations. Patients undergo SABR every other day for 5 fractions. Within 4-12 weeks of completion of SABR, patients undergo surgical resection with sentinel lymph node biopsy.

ARM II: Beginning 1 week before the start of SABR, patients undergo a caloric restriction diet for 6-12 weeks (for the duration of radiation treatment, until post radiation follow-up appointment) consisting of reducing calorie intake by 25%. Patients undergo SABR every other day for 5 fractions. Within 4-12 weeks of completion of SABR, patients undergo surgical resection with sentinel lymph node biopsy.

After completion of study intervention, patients are followed up at 3-6 weeks, and then 6 months after surgery.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nicole Simone, MD; Phone Number: 215-955-8874; Email: Nicole.Simone@jefferson.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University Hospital
      • Contact: Nicole Simone, MD; Phone Number: 215-955-6702; Email: Nicole.Simone@jefferson.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• • Patients with pathologically proven DCIS or invasive breast cancer histologies
• Willing and able to provide informed consent
• Willing and able to comply with study treatments including dietary intervention
• Body mass index (BMI) >= 21 at time of enrollment

• Age >= 40 years at time of consent

  * Patients with triple negative breast cancer (TNBC) must be >= 50 years of age at time of consent

• Karnofsky performance status (KPS) score 70 - 100
• Tumor size =< 3.0 cm

• Gross disease within the breast must be unifocal

  * Gross disease may be multifocal as long as the total extent of tumor, gross and microscopic, occupies a volume with greatest dimension =< 3 cm

• Patients with invasive disease are required to have clinical axillary staging including axillary ultrasound (US) that proves patient is clinically node negative or can be done by physical examination if the patient is over 70
• Patient is not being considered for preoperative chemotherapy
• Must be English or Spanish speaking

Exclusion Criteria:

• Patient is clinically node positive: clinically suspicious axillary lymph node(s) by axillary US or exam unless biopsied and found to be negative

• Patient has stage IV metastatic disease

  * Patients with oligo-metastatic disease who are being treated with curative intent per the treating physician will not be excluded if all other eligibility criteria are met

• Breast tumor size is > 3.0 cm
• Positive non-axillary sentinel nodes or evidence of suspicious supraclavicular, infraclavicular, or internal mammary nodes by imaging or physical exam, unless biopsied and found to be negative for tumor
• Evidence by physical examination or mammography of other suspicious masses, densities, or microcalcifications in either breast, unless biopsied and found to be benign
• Paget's disease of the nipple
• Previous breast radiation on ipsilateral side
• Any prior treatment with radiation therapy or chemotherapy for the current breast cancer diagnosis prior to registration
• Patients with significant psychiatric illness that would preclude them from adhering to the protocol in the judgement of the treating clinician
• BMI < 21 at the time of study enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I (standard dietary recommendations, SABR, surgery); Patients receive standard dietary recommendations. Patients undergo SABR every other day for 5 fractions. Within 4-12 weeks of completion of SABR, patients undergo surgical resection with sentinel lymph node biopsy.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Procedure: Resection; Undergo surgical resection; Other Names: Resection, resection, Surgical Resection, SURGICAL RESECTION, Surgical Resection, Surgical Resection, Surgical Resection; Radiation: Stereotactic Body Radiation Therapy; Undergo SABR; Other Names: SABR, SBRT, SBRT, Stereotactic Ablative Body Radiation Therapy, stereotactic body radiation therapy; Procedure: Sentinel Lymph Node Biopsy; Undergo sentinel lymph node biopsy; Other Names: SENTINEL LYMPH NODE BIOPSY, sentinel lymph node biopsy, Sentinel Node Biopsy, Sentinel node biopsy alone, SLNB, SNB; Other: Best Practice; Given standard dietary recommendations; Other Names: best practice, standard of care, standard of care, standard therapy; Procedure: Mammography; Undergo mammography; Other Names: Mammography, MAMMOGRAPHY, mammography, MG; Procedure: Biospecimen Collection; Undergo blood, tissue, and rectal swab sample collection; Other Names: Biological Sample Collection, Biological Sample Collection, Biospecimen Collected, Biospecimen Collection, Specimen Collection
Experimental: Arm II (caloric restriction diet, SABR, surgery); Beginning 1 week before the start of SABR, patients undergo a caloric restriction diet for 6-12 weeks (for the duration of radiation treatment, until post radiation follow-up appointment) consisting of reducing calorie intake by 25%. Patients undergo SABR every other day for 5 fractions. Within 4-12 weeks of completion of SABR, patients undergo surgical resection with sentinel lymph node biopsy.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Procedure: Resection; Undergo surgical resection; Other Names: Resection, resection, Surgical Resection, SURGICAL RESECTION, Surgical Resection, Surgical Resection, Surgical Resection; Radiation: Stereotactic Body Radiation Therapy; Undergo SABR; Other Names: SABR, SBRT, SBRT, Stereotactic Ablative Body Radiation Therapy, stereotactic body radiation therapy; Procedure: Sentinel Lymph Node Biopsy; Undergo sentinel lymph node biopsy; Other Names: SENTINEL LYMPH NODE BIOPSY, sentinel lymph node biopsy, Sentinel Node Biopsy, Sentinel node biopsy alone, SLNB, SNB; Other: Dietary Intervention; Undergo a caloric restriction diet; Other Names: Dietary Modification, intervention, dietary, Nutrition Intervention, Nutrition Interventions, Nutritional Interventions; Procedure: Mammography; Undergo mammography; Other Names: Mammography, MAMMOGRAPHY, mammography, MG; Procedure: Biospecimen Collection; Undergo blood, tissue, and rectal swab sample collection; Other Names: Biological Sample Collection, Biological Sample Collection, Biospecimen Collected, Biospecimen Collection, Specimen Collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent reduction in cellularity of breast tumor	The mean percent reduction will be compared between the study arms using a two-sample two-sided t-test with alpha 0.05.	4-16 weeks, depending on the date of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of positive margins and need for re-excision	Positive margin is defined as the presence of invasive carcinoma at the inked margin of the submitted operative specimen that does not appear to have significant radiation effect. The same definition will be applied to ductal carcinoma in situ (DCIS); however, there should be a 2mm margin on DCIS from the inked edge of the operative specimen. Will be compared between the study arms using a two-sample two-sided Fisher's exact with alpha 0.05.	Up to 6 months after SABR
Rate of post-operative complications	The presence or absence of the following potential adverse effects will be assessed: infection/cellulitis requiring antibiotics, wound dehiscence or open wound, and persistent seroma requiring aspiration. Will be compared between the study arms using a two-sample two-sided Fisher's exact with alpha 0.05.	Up to 6 months after SABR
Feasibility of identifying sentinel lymph node (SLN)	Sentinel lymph node biopsy performed at the time of surgical resection per standard institutional protocol including dual tracer SLN identification. The first 10 enrolled patients who have a SLN biopsy performed (decided per institutional protocol and surgeon standard practice)will be assessed to determine the feasibility of identifying sentinel lymph node after pre-operative SABR and if the rate of SLN mapping is not at least 95% the trial will be closed to accrual and modified to reflect the safety and feasibility of finding the sentinel node.	After pre-operative SABR
Global physiologic assessment	Weight, height, and body composition will be assessed. Calipers will be used to assess biceps, triceps, scapula, and hips. Bioimpedence will be used to measure percent body fat and muscle mass.	Up to 6 months after SABR
Change in patient-reported health-related quality of life	Psycho-social evaluation will be done using the Patient Reported Outcomes Measurement Information System cancer fatigue short form, the National Comprehensive Cancer Network distress thermometer, and Functional Assessment of Cancer Therapy-Breast measure to determine how the interventions affect the patients prior to intervention, just before surgery, and end of treatment visit post SABR completion.	Baseline to 6 months after SABR
Physician cosmesis evaluation	Physicians will evaluate cosmesis using the excellent, good, fair, poor scale at the times specified in the Study Schedule.	Up to 6 months after SABR
Change in tumor stiffness, angiogenesis, and tumor size	Contrast-enhanced mammography and ultrasound shear-wave elastography will be done at baseline and just before surgical intervention to determine if diet improves tumor stiffness and angiogenesis as well as size of tumor. Will be compared between the study arms using a two-sample two-sided t-test with alpha 0.05.	Baseline and before surgery

Collaborators and Investigators

• Sponsor: Thomas Jefferson University
• Investigators: Principal Investigator: Nicole Simone, MD, Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2021
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: April 27, 2021
• First Submitted That Met QC Criteria: July 8, 2021
• First Posted (Actual): July 13, 2021

Study Record Updates

• Last Update Posted (Actual): January 23, 2026
• Last Update Submitted That Met QC Criteria: January 21, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Skin Diseases; Breast Diseases; Carcinoma; Neoplasms, Ductal, Lobular, and Medullary; Breast Neoplasms; Carcinoma in Situ; Skin and Connective Tissue Diseases; Breast Carcinoma In Situ; Triple Negative Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Health Services Administration; Health Care Quality, Access, and Evaluation; Investigative Techniques; Therapeutics; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Biopsy; Cytodiagnosis; Quality of Health Care; Diet, Food, and Nutrition; Physiological Phenomena; Quality Indicators, Health Care; Nutritional Physiological Phenomena; Diagnostic Techniques, Surgical; Nutrition Therapy; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Guidelines as Topic; Quality Assurance, Health Care; Lymph Node Excision; Methods; Standard of Care; Diet; Specimen Handling; Radiosurgery; Diet Therapy; Practice Guidelines as Topic; Sentinel Lymph Node Biopsy
• Other Study ID Numbers: 20D.876; JT 12711 (Other Identifier: JeffTrial Number)

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