Phase II Trial of Capecitabine in Combination With Fulvestrant for Postmenopausal Women With Hormone Receptor Positive Metastatic Breast Cancer

Inclusion Criteria:

- Provide written informed consent prior to study-specific screening procedures, with
the understanding that the patient has the right to withdraw from the study at any
time, without prejudice.

- At least 18 years of age.

- Post-menopausal female (ie, amenorrheic for at least 12 months prior to study entry).
Post-menopausal status will be confirmed by drawing follicle stimulating hormone
(FSH) and estradiol levels if < 2 years since last menses.

- Ambulatory outpatient with Eastern Cooperative Oncology Group (ECOG)performance
status of 0 to 2 at study entry.

- Primary tumor human epidermal growth factor receptor 2 (HER-2) negative at study
entry.(Investigator discretion will be used in instances of immuno-histochemistry
[IHC] 2+.)

- Histologically or cytologically confirmed MBC.

- Primary tumor and/or metastatic lesion estrogen receptor + and/or progesterone
receptor + by IHC.

- At least one measurable or evaluable(non-measurable) lesion according to Response
Evaluation Criteria in Solid Tumors (RECIST) criteria (see Appendix 11.6) which has
not been irradiated (i.e., newly arising lesions in previously irradiated areas are
accepted). Ascites, pleural effusion, and bone metastases are not considered
measurable but are considered evaluable (non-measurable). Minimum indicator lesion
size for measurable disease: ≥10 mm measured by spiral computed tomography (CT) or
≥20 mm measured by conventional techniques.

- Adequate hematologic, renal, and hepatic function.

- Hematologic values: Neutrophils (ANC) > 1.5 x 109/L; Platelet count > 100 x
109/L.

- Renal function: estimated creatinine clearance > 30 mL/min as calculated with
Cockcroft-Gault equation.

- Note: In patients with moderate renal impairment (calculated creatinine
clearance 30 to 50 mL/min) at baseline, a dose reduction to (-1) of the
capecitabine starting dose is required.

- Serum bilirubin < 1.5 x upper limit normal (ULN).

- Alanine transaminase (ALT) or aspartate transaminase (AST) < 2.5 x ULN (or < 5 x
ULN in the case of liver metastases).

- Alkaline phosphatase < 2.5 x ULN (or < 5 x ULN in the case of liver metastases
or < 10 x ULN in the case of bone disease).

- International normalization ratio (INR) < 1.6.

- Must have ≤ 1 prior regimen of endocrine therapy for metastatic breast cancer. This
would include patients who have a recurrence while on adjuvant hormone therapy OR
have first recurrence after adjuvant hormone therapy OR progressed after first line
hormone therapy for metastatic breast cancer OR treatment naïve patients who present
with metastatic breast cancer.

Exclusion Criteria:

- Prior administration of capecitabine.

- Prior administration of fulvestrant.

- Prior chemotherapy for metastatic breast cancer.

- Radiotherapy ≤ 2 weeks prior to registration, except if to a non-target lesion only
or single-dose radiation for palliation. NOTE: Prior radiation to a target lesion(s)
is permitted only if there has been clear progression of the lesion since radiation
was completed.

- Life expectancy <3 months.

- Serious, uncontrolled, concurrent infection(s).

- Prior unanticipated severe reaction to fluoropyrimidine therapy, or known
hypersensitivity to 5-fluorouracil or known dihydropyrimidine dehydrogenase (DPD)
deficiency.

- Treatment for other carcinomas within the last 5 years, except cured non-melanoma
skin and treated in-situ cervical cancer or superficial bladder tumors (stage Ta or
Tis).

- Participation in any investigational drug study within 4 weeks preceding the start of
study treatment.

- Clinically significant cardiac disease (e.g., congestive heart failure, symptomatic
coronary artery disease and cardiac arrhythmias not well controlled with
medication)or myocardial infarction within the last 12 months prior to study entry.

- Active brain metastases. Patients with neurological symptoms must undergo a CT scan
or magnetic resonance imaging (MRI) of the brain to exclude active brain metastasis.
NOTE: Patients with treated brain metastases are eligible provided they have no
evidence of disease and are off definitive therapy (including steroids) ≥ 3 months
prior to study entry.

- Central nervous system (CNS) disorders or psychiatric disability judged by the
investigator to be clinically significant, precluding informed consent, or
interfering with compliance of oral drug intake.

- Known human immunodeficiency virus or chronic hepatitis B or C.

- Other serious uncontrolled medical conditions that the investigator feels might
compromise study participation.

- Major surgery within 4 weeks of the start of study treatment, without complete
recovery.

- Lack of physical integrity of the upper GI tract or malabsorption syndrome.

- Known, existing uncontrolled coagulopathy.

- Any of the following laboratory values:

- Abnormal hematologic values (neutrophils [ANC]: <1.5 × 109/L, platelet count:
<100 × 109/L)

- Impaired renal function (estimated creatinine clearance: <30 mL/min as
calculated with Cockcroft-Gault equation). Note: In patients with moderate renal
impairment (calculated creatinine clearance: 30 to 50 mL/min) at baseline, a
dose reduction to (-1) of the capecitabine starting dose is required.

- Serum bilirubin >1.5 × upper normal limit (ULN).

- Alanine transaminase (ALT) or aspartate transaminase (AST) >2.5 × ULN (or >5 ×
ULN in the case of liver metastases).

- Alkaline phosphatase > 2.5 × ULN (or >5 × ULN in the case of liver metastases or
>10 × ULN in the case of bone disease).

- International normalization ratio (INR) >1.6.

- History of:

- Bleeding diathesis,(ie, disseminated intravascular coagulation [DIC], clotting
factor deficiency) or

- Long-term anticoagulant therapy,(other than antiplatelet therapy and warfarin 1
mg qd for port prophylaxis).

- History of hypersensitivity to active or inactive excipients of fulvestrant (ie,
castor oil or Mannitol).

- Unwillingness to give written informed consent.

- Unwillingness to participate or inability to comply with the protocol for the
duration of the study.