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

Not Applicable

Recruiting

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

• Registration Number: NCT04959474
• Lead Sponsor: Thomas Jefferson University

Brief Summary

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.

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 Timeline

• Study First Submitted: 2021-04-27
• Study First Submitted QC: 2021-07-08
• Study First Posted: 2021-07-13
• Study Start: 2021-08-23
• Status Verified: 2025-03
• Last Update Submitted: 2025-04-23
• Last Update Posted: 2025-04-27
• Primary Completion: 2025-11-01
• Study Completion: 2026-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

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 axillary staging including axillary ultrasound (US) that proves patient is clinically node negative

• 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (standard dietary recommendations, SABR, surgery)	Questionnaire Administration	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 (caloric restriction diet, SABR, surgery)	Questionnaire Administration	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.
Arm I (standard dietary recommendations, SABR, surgery)	Best Practice	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 I (standard dietary recommendations, SABR, surgery)	Stereotactic Body Radiation Therapy	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 (caloric restriction diet, SABR, surgery)	Resection	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.
Arm II (caloric restriction diet, SABR, surgery)	Quality-of-Life Assessment	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.
Arm II (caloric restriction diet, SABR, surgery)	Sentinel Lymph Node Biopsy	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.
Arm I (standard dietary recommendations, SABR, surgery)	Resection	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 I (standard dietary recommendations, SABR, surgery)	Sentinel Lymph Node Biopsy	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 I (standard dietary recommendations, SABR, surgery)	Quality-of-Life Assessment	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 (caloric restriction diet, SABR, surgery)	Stereotactic Body Radiation Therapy	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.
Arm II (caloric restriction diet, SABR, surgery)	Dietary Intervention	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Change in patient-reported health-related quality of life	Baseline to 6 months after SABR	Calculated using following Scales - Psycho-social evaluation assessed using Patient Reported Outcomes Measurement Information System cancer fatigue short form The National Comprehensive Cancer Network distress thermometer Functional Assessment of Cancer Therapy-Breast measure
Feasibility of identifying sentinel lymph node (SLN)	4-16 weeks, depending on the date of surgery	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.
Rate of post-operative complications	Up to 6 months after SABR	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.
Global physiologic assessment	3-6 weeks, depending on the radiation schedule	Calculated by following measures- Bioimpedence will be used to measure percent body fat and muscle mass. Weight, height, and body composition will be assessed. Calipers will be used to assess biceps, triceps, scapula, and hips.
Physician cosmesis evaluation	Up to 6 months after SABR	Cosmesis evaluation using the excellent, good, fair, poor scale at the times specified in the Study Schedule.
Change in tumor	3-6 weeks, depending on the radiation schedule	Stiffness, Angiogenesis, and Tumor size are assessed- 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.
Rate of positive margins and need for re-excision	Up to 6 months after SABR	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.

Trial Locations

Locations (1)

Thomas Jefferson University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States