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
- 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
- serum creatinine <= 2 x ULN, or calculated creatinine clearance >45 mL/min
according to Cockroft and Gault formula).
- 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
- 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 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.