Phase II Trial of Capecitabine With Fulvestrant for Postmenopausal Women With Hormone Receptor Positive Metastatic Breast Cancer
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: capecitabine; fulvestrant
Intervention description: Capecitabine will be given on a continuous basis at a total dose of 1500 mg, given as 1000 mg po in the morning (AM) and 500 mg po in the evening (PM) in patients of body weight < 80 Kg, and at a total dose of 2000 mg given as 1000 mg po bid in patients with a body weight of ≥80 Kg.; Fulvestrant will be given at 500mg on Day 1 followed by 250 mg on Days 15 and 29, then 250mg every 28 days(Q28d).
Intervention MeSH terms: Capecitabine; Fulvestrant
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hormone; Receptor; Positive; Metastatic; Breast; Cancer

Summary:

      The purpose of this study is to determine if the combination of continuous daily capecitabine
      with fulvestrant on a loading dose schedule will delay disease progression in metastatic
      breast cancer (MBC) patients.
    

Eligibility criteria:

        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.