This is a Phase 2 study for patients with resected Stage I-III HR+/HER2-negative breast cancer with detected molecular residual disease (MRD+) following standard neo/adjuvant and locoregional therapy delivered with curative intent. In this study participants will be treated with capecitabine. Capecitabine will be administered orally at a dose of 500 mg 3 times daily for up to 12 months, or until the time of clinical recurrence, discontinuation due to toxicity, or withdrawal of consent. This study will have two stages, stage 1 would enroll up to 8 participants to clear the Minimal Residual Disease (MRD) and Stage 2 will enroll up to 5 participants. The purpose of this study is to determine if this study population would have a better outcome from receiving capecitabine rather than having no change in treatment if MRD is detected.
Male or female patients ≥ 18 years of age with histologically confirmed (by local assessment with ASCO/CAP criteria), resected ER-positive/HER2-negative stage I-III breast cancer
Evidence of MRD (positive test by the Pathlight assay) despite standard adjuvant therapy
No contraindications to capecitabine (including absence of DPYD variants that in the opinion of the investigator are a contraindication to metronomic capecitabine)
No clinical or radiographic evidence of recurrent or metastatic disease
Prior therapy with capecitabine.
Previous or concurrent malignancy within 3 years of study entry, with the following exceptions: adequately treated basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, or other non-invasive or indolent malignancy; other solid tumors treated curatively without evidence of recurrence for at least 3 years prior to study entry.
History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) <6 months prior to screening,
Symptomatic chronic heart failure (e.g., New York Heart Association Class ≥ 2), history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality <6 months prior to screening except atrial fibrillation and paroxysmal supraventricular tachycardia.
Single group
Capecitabine
DrugCapecitabine 500 mg
Clearance rate of ctDNA at 16 weeks after the use of metronomic capecitabine measured using the Pathlight assay in patients with molecular residual disease (MRD). ctDNA clearance is defined as no detection of plasma ctDNA.
Distant recurrence free survival (DRFS).
Describe clinical outcomes for MRD+ patients treated with this escalated strategy, including distant recurrence free survival (DRFS).
Number and severity of treatment related adverse events as assessed by CTCAE v5.0.
Measure ctDNA levels in MRD positive patients using the Pathlight assay after initiation of metronomic capecitabine.
Number of patients with detectable residual disease and early treatment response using novel liquid biopsy.
Proportion of patients with ctDNA clearance (defined as undetectable by the tumor-informed personalized ctDNA assay) and log-fold change in ctDNA quantification.
Proportion of patients with ctDNA clearance (defined as undetectable by the tumor-informed personalized ctDNA assay) and log-fold change in ctDNA quantification from baseline, stratified by tumor genomic features (somatic mutations, structural variants, and copy number alterations identified by whole-genome sequencing of tumor tissue), following capecitabine initiation in patients with molecular residual disease (MRD), in order to identify molecular determinants of ctDNA response.
Frequency of tumor genomic alterations associated with subsequent development of ctDNA-detected molecular residual disease and treatment resistance during adjuvant surveillance and intervention in patients with primary ER+/HER2- breast cancer.
Frequency of tumor genomic alterations (somatic mutations, structural variants, and copy number alterations identified by whole-genome sequencing of primary tumor tissue) associated with subsequent development of ctDNA-detected molecular residual disease (MRD) and treatment resistance (defined as ctDNA non-clearance or recurrence on tumor-informed personalized ctDNA assay) during adjuvant surveillance and intervention in patients with primary ER+/HER2- breast cancer.
Type of tumor genomic alterations associated with subsequent development of ctDNA-detected molecular residual disease and treatment resistance during adjuvant surveillance and intervention in patients with primary ER+/HER2- breast cancer.
Type of tumor genomic alterations (somatic mutations, structural variants, and copy number alterations identified by whole-genome sequencing of primary tumor tissue) associated with subsequent development of ctDNA-detected molecular residual disease (MRD) and treatment resistance (defined as ctDNA non-clearance or recurrence on tumor-informed personalized ctDNA assay) during adjuvant surveillance and intervention in patients with primary ER+/HER2- breast cancer.
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