Overview

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.

Eligibility

Inclusion Criteria:

• 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
• Previous Therapy requirements: (i) Received at least 24 months of adjuvant endocrine therapy, including 6 months of an aromatase inhibitor and (i) Received at least 12 months of adjuvant CDK4/6i if indicated, unless not tolerated or declined
• ECOG performance status of 0-1.
• Patient must have adequate organ function as determined by the following:
  1. Renal function:
• Serum creatinine \< 1.5 x ULN (upper limit of normal range) or a calculated creatinine clearance of \> 50mL/min using the Cockcroft-Gault formula b. Bone marrow function (without hematopoietic growth factors or transfusion):
• Absolute neutrophil count (ANC) \> 1.0 x 109/L
• Hemoglobin \> 90 g/L or \> 9g/dL
• Platelets \> 75 x 109/L c. Liver function:
• Total bilirubin ≤ 1.5 × ULN and \< 35 uMol/L; OR total bilirubin \>1.5 × ULN with indirect bilirubin \< 1.5 × ULN.
• Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) \< 2.5 x ULN.
• Female participants of childbearing potential must have a negative serum β-HCG test result at enrolment.
• Female participants of childbearing potential must agree to use methods of contraception that are highly effective.
• Male participants must agree to use methods of contraception that are highly effective.
• The participant is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Signed written and voluntary informed consent.

Exclusion Criteria:

• 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.
• Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following:
  1. History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) \<6 months prior to screening,
  2. 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.
  3. Uncontrolled hypertension defined as persistent elevation of systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100mmHg, despite current therapy.
• Known positive serology for HIV (Human immunodeficiency virus) that is not currently controlled with antiretroviral therapy.
• Has a known history of or is positive for active hepatitis B or hepatitis C unless adequate viral suppression is achieved. Participants who have had definitive treatment for HCV are permitted if HCV RNA is undetectable at Screening Visit.
• Impaired gastrointestinal function or disease that may significantly alter the absorption of capecitabine.
• Medical, psychiatric, cognitive, or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol, or complete the study.