Abstract OT-19-01: Phase I study to evaluate the safety and feasibility of preoperative ablative radiotherapy (SABER) for selected early stage breast cancer

Background: Breast conserving therapy is an established option for early stage breast cancer. Shorter postoperative radiotherapy (RT) regimens have similar efficacy in lower risk breast cancer, including hypofractionated whole breast RT and Accelerated Partial Breast Irradiation (APBI). Despite similar efficacy results for APBI, RAPID trial showed worse cosmetic outcomes for patients receiving APBI compared to whole breast RT. Larger postoperative lumpectomy cavity volumes and the used dose regimen could have had an impact on cosmesis. There are only few published preoperative APBI pilot studies with different dosimetric schemes treating smaller RT target volumes that would potentially translate into less toxicity. Our study is designed to evaluate the safety and feasibility of preoperative ablative RT in patients with early stage breast cancer. An array of ancillary imaging, blood and tissue biomarker collection is also planned in order to study the radiation response in breast cancer. Trial Design: This phase I study uses a modification of the standard 3+3 Phase I design to identify the recommended phase 2 dose of preoperative SABER for treatment of selected breast cancer patients. Participants will be treated with assigned dose level of preoperative SABER, once a day, for 5 fractions given on non-consecutive days, over a period of 2 weeks. The tested dose levels are: Level I=35 Gy (7 Gy x 5), Level II (starting dose)= 40 Gy (8 Gy x 5), Level III=45 Gy (9 Gy x 5), Level IV=50 Gy (10 Gy x 5). Standard partial mastectomy and axillary surgery will be performed 4-6 weeks after preoperative SABER. Adjuvant systemic therapy will be per standard of care. Exploratory studies will be performed pre/post RT and postoperative, including multiparametric breast MRI, biomarkers in blood (CTC’s, SNPs, cytokines, CRP) and tissue (assessment of radiation response, expression of PD-L1, PD1, TILs). Cosmesis and QoL assessment will be performed at scheduled 1, 6, 12, 24 months follow-up. Eligibility criteria: Women, 50 or older, clinical stage T1 unifocal, N0, ER/PR+/HER2 negative, ECOG 0-1, able to undergo MRI with contrast are eligible. Specific Aims: Aim 1. To identify the recommended phase II dose of preoperative SABER; Aims 2.a) to determine the safety, tolerability, Dose Limiting Toxicity (DLT) and toxicity profile of delivering SABER; b) to determine the rate of complete pathological response after preoperative SABER; c) To assess cosmetic results (by MD and patient’s assessment) and QoL after SABER and standard partial mastectomy/axillary surgery. Exploratory aims: a) to determine biomarkers in blood and tissue, and multiparametric MRI radiographic changes and associate them with toxicity and radiation tumor response; b) to assess locoregional recurrence, disease-free survival, and overall survival; c) to assess sentinel lymph node biopsy identification rates after SABER. Statistical Methods: In this novel phase I study, escalation to the next higher dose level will occur only if 0 or only 1 out of 6 patients has DLT. Present accrual and target accrual: A total of 12 to 18 evaluable patients will be enrolled. Expected enrollment period is 3 years and time to complete the study is about 5 years. Open for accrual in 06/2020. Clinical trial information:NCT04360330 Citation Format: Cristiane Takita, Isildinha M. Reis, Radka Stoyanova, John C. Ford, Brian Marples, Jose Net, Monica Yepes, Carmen Gomez, Susan Kesmodel. Phase I study to evaluate the safety and feasibility of preoperative ablative radiotherapy (SABER) for selected early stage breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-19-01.