Phase II single-arm trial of low-dose capecitabine in patients with advanced breast cancer.

TPS1159 Background: Capecitabine is approved for use in both the adjuvant and metastatic settings of breast cancer. The clinical activity of capecitabine was established at the maximum tolerated dose of 1000–1250 mg/m² given on days 1–14 of a 21-day cycle. As seen with other cytotoxic agents, dose escalation may lead to increased toxicity without clear efficacy benefit, while lower, fixed-dose capecitabine maintains antitumor activity with fewer adverse effects, including diarrhea, hand–foot syndrome, mucositis, and neutropenia. This approach is especially important for older and frail patients, who are more vulnerable to toxicity and underrepresented in trials. Methods: This single-arm, open-label phase 2 study aims to evaluate the anti-tumor effect of continuous daily oral low-dose capecitabine at 1500mg in 40 patients aged 60 years or older, and/ or considered frail at any age (ECOG 0-2). Frailty is defined by the investigator as an individual at greater risk of complications and poorer outcomes with systemic therapy, secondary to a lower physiologic reserve and higher comorbidities and functional deficits. Eligible patients include those with HER2-negative unresectable or metastatic breast cancer (hormone positive or triple negative) with measurable disease, who have progressed on at least 1 prior line of therapy. Major exclusion criteria include HER2-positive breast cancer, severe hepatic or renal failure, inability to swallow pills, and uncontrolled CNS/ leptomeningeal disease. Patients will be evaluated for toxicity every 4 weeks and for response every three cycles using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Therapy will be continued until evidence of disease progression or unacceptable toxicity. The primary objective is the clinical activity of daily low dose capecitabine by overall response rates (ORR) per RECIST. The secondary objectives include progression-free survival (PFS), overall survival (OS), and determining the safety and tolerability of daily low dose capecitabine using the Common Terminology Criteria for Adverse Events (CTCAE) v.6.0. Exploratory analyses include evaluating quality of life, measurement of sarcopenia, geriatric assessment using the CARE (Cancer and Aging Resilience Evaluation) tool before registration and at the end of treatment, and evaluating adherence to capecitabine. Simon's two-stage minimax design will be used with a type I error rate of 0.05 and power of 80%. The null hypothesis response rate of 10% will be tested against a one-sided alternative response rate of 25%. In the first stage, 22 patients will be accrued. If there are 2 or fewer responses in the first 22 patients enrolled, the study will be discontinued. The trial was approved by the Institutional Review Board at the University of Alabama at Birmingham (UAB) and has been accruing since February 2025. 8 of the planned 40 patients have been enrolled. Clinical trial information: NCT06105684 .