Breast Radiotherapy (SABER) for the Treatment of Hormone Receptor Positive HER2 Negative Early Stage Breast Cancer

PRIMARY OBJECTIVE:

I. To determine the recommended phase II dose (RP2D) of preoperative stereotactic ablative breast radiotherapy (SABER) for selected patients with early stage breast cancer.

SECONDARY OBJECTIVES:

I. To determine the safety, tolerability, dose-limiting toxicity (DLT) and toxicity profile of delivering stereotactic ablative breast radiotherapy for selected patients with early breast cancer.

II. To determine the rate of complete pathological response after preoperative stereotactic ablative breast radiotherapy.

III. To assess cosmetic results (by physician and patients) and quality of life (QoL) assessment after preoperative ablative radiotherapy followed by standard partial mastectomy and axillary surgery.

EXPLORATORY OBJECTIVES:

I. To determine biomarkers in blood (circulating tumor cells [CTCs], single nucleotide polymorphisms [SNPs], cytokines, C-reactive protein [CRP]) and tissue (PD-L1, PD1, tumor-infiltrating lymphocytes [TILs]), and multiparametric breast magnetic resonance imaging (MRI) (MpMRI) radiographic changes and associate them with toxicity and radiation tumor response.

II. Local and regional recurrence, disease-free survival and overall survival.

III. To assess sentinel lymph node identification rates after preoperative SABER.

OUTLINE: This is a dose-escalation study.

Patients undergo SABER over 5 fractions once daily (QD) (on non-consecutive days) over 2 weeks in the absence of disease progression or unacceptable toxicity. Approximately 4-6 weeks later, patients undergo standard of care partial mastectomy and axillary surgery. Patients undergo computed tomography (CT) scan during screening and magnetic resonance imaging (MRI), tumor biopsy and blood sample collection throughout the study.

After completion of study treatment, patients are followed up at 1, 6, 12, and 24 months post-surgery, then periodically thereafter.