Combination of Oral WX-671 Plus Capecitabine vs. Capecitabine Monotherapy in First-line Her2-negative Metastatic Breast Cancer

A Phase 2, Two-arm, Double-blind, Multi-center, Randomized Study of the Combination of Oral WX-671 Plus Capecitabine vs. Capecitabine Monotherapy in First-line Her2-negative Metastatic Breast Cancer

This randomized, double-blind, placebo controlled phase II trial is studying how well capecitabine works when given in combination with WX-671 or when given alone in treating patients receiving first-line therapy for her2negative metastatic breast cancer.

Inclusion Criteria:

• Females aged ≥ 18 years

• Patients appropriate for palliative first-line, mono chemotherapy with capecitabine

• Histological or cytological confirmed, non-inflammatory metastatic breast cancer

• Availability of paraffin-embedded tumor tissue from the primary resection or biopsy of a metastatic lesion.

• HER2-negative breast cancer

• Complete staging within 2 weeks prior to randomization (4 weeks for bone scan).

• Radiologically confirmed disease

• ECOG performance status of ≤ 2

• Ability to understand and willingness to voluntarily sign and date a written informed consent form before screening

• Negative pregnancy test (urine or serum) within 3 days before first study drug for women of childbearing potential. Use of effective contraception during the study and for 3 months after stopping study drug treatment.

• Normal organ and marrow function as defined by laboratory parameters (obtained within the screening period) within the following limits:

  • neutrophils >= 1.5 x 109/L;
  • platelets >= 100 x 109/L;
  • hemoglobin >= 9.0 g/dL (5.6 mmol/L).
  • total bilirubin <= 1.5 x upper limit of normal (ULN);
  • aspartate aminotransferase (AST)/ALT <= 2.5 x ULN (< 5.0 x ULN for patients with liver metastases);
  • serum creatinine <= 2 x ULN, or calculated creatinine clearance >45 mL/min according to Cockroft and Gault formula).

Exclusion Criteria:

• Endocrine therapy completed within 2 weeks before the start of treatment (i.e. previous hormone therapy is allowed provided that there is a washout period of 2 weeks).
• Prior chemotherapy or biologic therapy for metastatic disease.
• Major surgery within 4 weeks prior to the start of treatment.
• Other anti-cancer treatment (e.g. hormones) within 2 weeks before the start of treatment.
• Treatment within 12 months with adjuvant 5-FU containing chemotherapy (regarded as indicating 5-FU resistance) and/or prior capecitabine therapy.
• Radiation therapy. Palliative radiation of stable, non-target lesions more than 2 weeks before the start of treatment is allowed, provided patients have recovered from the radiation side-effects.
• History of or radiological evidence of brain metastasis including previously treated, resected or asymptomatic brain lesions or leptomeningeal involvement.
• Active seizure disorder or history of cerebrovascular accident (CVA) or transient ischemic (TI) attack within the past 12 months.
• History of other malignancy within the last 3 years except for surgically cured non-melanoma skin cancer or cervical carcinoma in situ.
• Active cardiac disease e.g. unstable angina, congestive heart failure, myocardial infarction (MI) within the preceding 6 months.
• Any medical condition prohibiting standard imaging procedures
• Pregnant or breast-feeding.
• Any unrelated illness, e.g. active infection requiring parenteral antibiotics, inflammation, medical condition or laboratory abnormalities, which in the judgment of the investigator might significantly affect patients' study participation.
• Any surgical or medical condition that might significantly alter the absorption, distribution, metabolism or excretion of either study drug.
• Known hepatitis B/C or HIV (human immunodeficiency virus) infection.