Neoadjuvant Radiation in Locally Advanced Breast Cancer

Fudan University

Status and phase: Enrolling; Phase 2

Conditions: Breast Neoplasms

Treatments: Dietary Supplement: β-alanine; Radiation: Neoadjuvant radiotherapy; Radiation: Spatially fractionated radiotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT05479409

FDRT-BC016

Details and patient eligibility

About

The purpose of this study is to evaluate the efficacy and safety of neoadjuvant radiation therapy in improving local-regional control and facilitating surgical conversion in patients with inoperable locally advanced breast cancer after 2-6 courses of neoadjuvant chemotherapy. This study will also investigate whether beta-alanine supplementation and spatially fractionated radiotherapy can enhance the therapeutic response to neoadjuvant chemoradiotherapy. In addition, this study aims to explore tumor microenvironmental features and molecular biomarkers associated with treatment response, radioresistance, immune activation, and long-term outcomes.

Full description

RATIONALE:

The optimal management of patients with locally advanced breast cancer(LABC) remains unknown. Neoadjuvant chemotherapy is currently accepted as a standard treatment strategy for patients with inoperable LABC; however, a substantial proportion of patients do not achieve sufficient tumor regression and may remain unsuitable for surgery. For these patients, radiation therapy before surgery may provide an opportunity for further tumor downstaging, improve the chance of surgical conversion, and enhance local-regional control.

OUTLINE:

This is a prospective, open-label, multi-arm phase II study. Eligible patients are women with inoperable locally advanced breast cancer who remain unsuitable for surgery following 2-6 courses of neoadjuvant chemotherapy.

Patients will receive one of the following treatment strategies: neoadjuvant radiation therapy, beta-alanine supplementation plus neoadjuvant radiation therapy, or spatially fractionated radiotherapy.

The primary objective of this study is to evaluate the clinical efficacy of these radiation-based strategies, including local-regional control and surgical conversion. Secondary objectives include treatment safety, tumor response, pathological response when surgery is performed, and long-term clinical outcomes.

This study will also investigate early predictors of treatment response. Fresh tumor tissue and peripheral blood samples will be collected and stored before treatment for biomarker analysis. Molecular and tumor microenvironmental characteristics associated with radiotherapy sensitivity, radioresistance, immune activation, and treatment outcomes will be explored. Imaging assessments will be performed before and after treatment, and ultrasound-based parameters, including shear wave elastography, will be evaluated as potential early imaging predictors of treatment response.

Enrollment: 70 estimated patients

Sex: Female

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically or cytologically confirmed locally advanced breast carcinoma
• Inoperable with with 4-6 courses of prior chemotherapy
• No contradiction of radiation or chemo-radiotherapy
• Patients should have the ability to understand and the willingness to sign a written informed consent document
• Signed informed consent must be obtained prior to any study specific procedures

Exclusion criteria

• Other prior or concurrent malignancy except adequately treated squamous cell or basal cell skin cancer or contralateral breast DCIS
• Coagulation disorders
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, and cardiac arrhythmia
• Serious underlying medical illness with life expectancy less than 2 years.
• Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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70 participants in 3 patient groups

Neoadjuvant radiotherapy

Experimental group

Treatment:

Radiation: Neoadjuvant radiotherapy

β-alanine plus neoadjuvant radiotherapy

Experimental group

Treatment:

Radiation: Neoadjuvant radiotherapy

Dietary Supplement: β-alanine

Spatially fractionated radiotherapy

Experimental group

Treatment:

Radiation: Spatially fractionated radiotherapy