Clinical Trials

Inclusion Criteria

• Age ≥ 18 years.
• Histological confirmation of estrogen-receptor positive (ER+), HER2-negative overexpression or amplification negative as per ASCO/CAP guidelines, metastatic breast cancer.
• Measurable disease. Bone only disease allowed if associated with soft tissue component that is measurable by RECIST 1.1 criteria.
• ECOG Performance Status (PS) 0, 1 or 2.

The following laboratory values obtained ≤14 days prior to registration:

• Hemoglobin ≥ 9.0 g/dL, no transfusions allowed ≤ 14 days prior to registration. 
• Absolute neutrophil count (ANC) ≥ 1500/mm3
• Platelet count ≥ 100,000/mm3
• Total bilirubin ≤ 1.5 x ULN
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3 x ULN (≤ 5 x ULN for patients with liver involvement)
• PT/INR/aPTT ≤ 1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy
• Calculated creatinine clearance ≥45 ml/min using the Cockcroft-Gault formula below:
  Cockcroft-Gault Equation: Creatinine clearance for males = (140 - age)(weight in kg) / (72)(serum creatinine in mg/dL), Creatinine clearance for females = (140 - age)(weight in kg)(0.85) / (72)(serum creatinine in mg/dL)
• Negative serum or urine pregnancy test done ≤7 days prior to registration, for persons of childbearing potential only. NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Provide written informed consent.
• Ability to complete questionnaire(s) by themselves or with assistance.
• Willingness to provide mandatory blood specimens for correlative research
• Ability to undergo re-staging CT scans as required by the protocol.
• Willing to return to enrolling institution at the specified frequency for follow-up (during the Active Monitoring Phase of the study).

Exclusion Criteria

Prior chemotherapy or use of Antibody Drug Conjugate in the Metastatic setting.

Any of the following, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:

• Pregnant persons
• Nursing persons
• Persons of childbearing potential who are unwilling to employ adequate contraception

 Any of the following prior therapies:

• Major Surgery ≤ 3 weeks prior to registration 
• Radiation therapy ≤ 2 weeks prior to registration.
• Evidence of visceral crisis or impending cord compression.
• Evidence of uncontrolled brain metastasis requiring whole brain irradiation or intervention.

Uncontrolled intercurrent illness including, but not limited to:

• ongoing or active infection
• symptomatic congestive heart failure
• unstable angina pectoris
• uncontrolled cardiac arrhythmia
• chronic oxygen dependence
• respiratory failure
• or psychiatric illness/social situations that would limit compliance with study requirements.
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
• Other active malignancy ≤ 3 years prior to registration. EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix.
• If there is a history of prior malignancy, they must not be receiving other cancer specific treatment. Except for antiestrogen treatment (aromatase inhibitors or selective estrogen modulators) for their cancer are permitted if they meet other eligibility criteria. Denosumab and zolendronic acid, are permitted as established adjunct therapies per guidelines.  
• History of myocardial infarction ≤6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.
• Patients known to have certain homozygous or compound heterozygous DPYD variants that result in complete absence of DPD activity
• History of severe hypersensitivity reactions to fluorouracil or capecitabine

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 6/12/2024. Questions regarding updates should be directed to the study team contact.