Phase II Single Arm Trial of Low Dose Capecitabine in Patients with Advanced Breast Cancer

This is a phase II study aiming at evaluating capecitabine prospectively at a dose of 1000 mg once daily in patients with advanced breast cancer who are ≥60 years of age, or frail at any age, with a greater risk of complications and poorer outcomes with other treatments.

The study is a phase II, single arm study in which all patients will receive the study drug. Participants will include older/frail patients with metastatic breast cancer.

All patients will be treated with capecitabine 1000 mg daily. There will be a total of 40 participants with measurable disease on this trial.

The study will encompass participants with locally advanced unresectable/metastatic breast cancer with measurable disease, who progressed on at least 1 prior therapy in the metastatic setting. Breast cancer subtypes include HR+ HER2 negative, or TNBC, age ≥ 60 years old, or frail patients at a younger age. ECOG PS 0- 2.

The study will discontinue if progressive disease or unacceptable toxicity is noted.

Eligibility Criteria:
Inclusion Criteria:

1. Histologically or cytologically confirmed breast cancer with HER2 negative status. A copy of the pathology report is required at the time of enrollment.

   1. HER2 negativity will be determined by in situ hybridization (ISH) non- amplified and IHC 0 or 1+ or 2+.
   2. Patients with HR (hormone receptor) positive and triple negative breast cancer (TNBC) will be eligible for enrollment.
2. Metastatic or locally advanced breast cancer, with at least one measurable lesion according to RECIST (v1.1).
3. ECOG performance status of 0-2.
4. Patients must have progressed on at least 1 prior line of therapy in the metastatic setting (hormonal therapy or chemotherapy)
5. Adequate organ function as evidenced by:

   1. ANC \>1.5 x 10⁹/L (1500/µL) or \> 1.3 x 10⁹/L (1300/µL) for patients with history of benign ethnic neutropenia.
   2. Platelet count ≥100,000/µL (without transfusion within 2 weeks prior to initiation of study treatment (Cycle 1, day 1)).
   3. Hemoglobin ≥9.0 g/dl. Patients may be transfused or receive erythropoietic treatment to meet this criterion.
   4. AST, ALT, and alkaline phosphatase ≤2.5 x upper limit of normal (ULN) with following exceptions: I. Patients with documented liver metastasis: AST and ALT ≤5 x ULN II. Patients with documented liver or bone metastasis: alkaline phosphatase ≤5 x ULN
   5. Serum bilirubin ≤1.5 x ULN

      • Patients with known Gilbert disease who have serum bilirubin level ≤3 x ULN may be enrolled.
   6. INR and aPTT ≤1.5 x ULN

      • This applies only to the patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
   7. Creatinine clearance \> 30 mL/min (measured using Cockcroft-Gault equation or estimated glomerular filtration rate from the Modification of Diet in Renal Disease Study)
6. Patients must be able to provide signed informed consent.
7. Female patients of any ethnic group. Female patients must be surgically sterile, postmenopausal (no menses for at least one year), or using medically approved method of contraception (excluding rhythm, withdraw or abstinence). Men must agree to use a medically approved method of contraception (excluding rhythm, withdraw or abstinence).
8. Patients ≥60 years old and/or frail patients at any age, 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.
9. Complete initial work-up within 2 weeks prior to start of treatment (Cycle 1 Day 1).
10. Patients known to be HIV positive are eligible if they meet the inclusion criteria.

Exclusion Criteria:

1. Any history of treatment with Capecitabine in metastatic setting.
2. Patients who only have non-measurable disease.
3. Patients with severe hepatic (bilirubin \> 3 times upper limit of normal) or renal failure (CrCl \< 30 calculated using Cockcroft-Gault formula).
4. Patients who are unable to swallow pills
5. Patients with HER2 positive breast cancer
6. Major surgical procedure within 3 weeks prior to study entry.
7. Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for \>2 weeks prior to initiation of study treatment (Cycle 1, Day 1)