Abstract P3-10-18: Phase II Single Arm Trial of Low Dose Capecitabine in Patients with Advanced Breast Cancer (NCT06105684)

Abstract Background: Capecitabine (Xeloda), an oral prodrug of fluorouracil, is approved for adjuvant and advanced stage treatment of breast cancer. The approved dose of capecitabine is determined based on studies in heavily pretreated patients, which demonstrated responses at the maximum tolerated dose of 1000-1250 mg/m2 on days 1-14 of a 21-day cycle. However, higher doses of other chemotherapy agents have resulted in increased toxicity without necessarily improving response rates. Multiple studies used capecitabine at lower, fixed doses, demonstrating maintained efficacy and notable reductions in toxicities (diarrhea, palmar-plantar erythrodysesthesia, mucositis, and neutropenia). Older adults and frail individuals experience more severe treatment-related side effects and are often underrepresented in clinical trials due to presumed frailty or implicit bias of investigators. This study aims to evaluate both efficacy and tolerability of a daily lower dose of capecitabine in the treatment of advanced HER2-negative breast cancer in aging and frail populations. Methods: This single-arm, open-label phase 2 study will evaluate the anti-tumor effect of continuous daily oral low-dose capecitabine at 1500mg in 40 patients of age 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 using the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30), and the PRO-CTCAE (Patient reported outcomes- Common Terminology Criteria for Adverse Events) questionnaire. Other exploratory analyses include measurement of sarcopenia: measuring body composition including skeletal muscle index (SMI) calculated from skeletal muscle area on CT scan before, during, and after treatment, as well as evaluating geriatric assessment using the CARE (Cancer and Aging Resilience Evaluation) tool prior to 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 opened to accrual July 2024. Citation Format: Vinod Kumar, Nusrat Jahan, Gabrielle B. Rocque, Lisle Nabell, Sejong Bae, Anethea Tolliver, Nuzhat Rahman Siddiqui, Grant Williams, John Carpenter, Erica M. Stringer-Reasor, Katia Khoury. Phase II Single Arm Trial of Low Dose Capecitabine in Patients with Advanced Breast Cancer (NCT06105684) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-10-18.