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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Другое Best Practice
  Given standard dietary recommendations
• Лучевая терапия Stereotactic Body Radiation Therapy
  Undergo SABR
• Процедура Resection
  Undergo surgical resection
• Процедура Sentinel Lymph Node Biopsy
  Undergo sentinel lymph node biopsy
• Другое Dietary Intervention
  Undergo a caloric restriction diet
• Другое Questionnaire Administration
  Ancillary studies
• Другое Quality-of-Life Assessment
  Ancillary studies
• Процедура Mammography
  Undergo mammography
• Процедура Biospecimen Collection
  Undergo blood, tissue, and rectal swab sample collection

Первичные конечные точки

• Percent reduction in cellularity of breast tumor [Срок оценки: 4-16 weeks, depending on the date of surgery]

Вторичные конечные точки (7)

• Feasibility of identifying sentinel lymph node (SLN) [Срок оценки: After pre-operative SABR]
• Global physiologic assessment [Срок оценки: Up to 6 months after SABR]
• Change in patient-reported health-related quality of life [Срок оценки: Baseline to 6 months after SABR]
• Physician cosmesis evaluation [Срок оценки: Up to 6 months after SABR]
• Rate of positive margins and need for re-excision [Срок оценки: Up to 6 months after SABR]
• Rate of post-operative complications [Срок оценки: Up to 6 months after SABR]
• Change in tumor stiffness, angiogenesis, and tumor size [Срок оценки: Baseline and before surgery]

Критерии участия

Критерии включения

• • 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Thomas Jefferson University Hospital — Philadelphia

Идентификаторы

NCT: NCT04959474 · 20D.876 · JT 12711

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗