A Dose-escalating, Multicenter, Single Arm, Open-Label Study of XRP9881 in Combination With Capecitabine (Xeloda), in Metastatic Breast Cancer Patients With Disease Progressing After Anthracycline and Taxane Therapy
- Histologically or cytologically proven diagnosis of breast adenocarcinoma that is now
metastatic or locally recurrent and inoperable with curative intent.
- Prior treatment with a standard regimen of anthracycline and taxane.
- Female patients at least 18 years old.
- ECOG performance status (PS): 0-2
- Adequate organ and bone marrow function
- Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
(For the part I component, patients with non-measurable disease are accepted.)
- Resolution of all clinically significant toxic effects
- Completion of all prior therapy ≥ 3 weeks prior to registration. Patients on
bisphosphonate therapy may continue such therapy.
- Patients must be either post-menopausal, surgically sterile, or using effective
- Willing and able to comply with study procedures and sign informed consent
- History of any second malignancy within the last 5 years (except adequately treated
basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix uteri).
- Patients receiving more than one adjuvant regimen or more than one metastatic regimen
- Known brain or leptomeningeal disease.
- Concurrent treatment on another clinical trial or with any other cancer therapy
including chemotherapy, biological therapy, hormonal therapy, radiotherapy,
chemoembolization therapy, cryotherapy, targeted non-cytotoxic therapies, or patients
planning to receive these treatments during the study.
- Prior treatment with capecitabine, XRP9881, or any investigational chemotherapy.
- History of hypersensitivity to taxanes, Polysorbate-80, or to compounds with similar
chemical structures. Patients with known intolerance to fluoropyrimidines or patients
with known dihydropyrimidine dehydrogenase (DPD) deficiency.
- Concurrent treatment with potent inhibitors of cytochrome P450 3A4, or patients
planning to receive these treatments. For patients who were receiving treatment with
such agents, a one-week washout period is required prior to registration.
- Peripheral neuropathy grade ≥ 2.
- Any of the following within the 6 months prior to registration: myocardial
infarction, severe/unstable angina, coronary/peripheral artery bypass graft surgery,
clinically symptomatic and uncontrolled cardiovascular disease, or clinically
significant cardiac arrhythmias (grade 3-4).
- History of inflammatory bowel disease or chronic diarrhea.
- Lack of physical integrity of the upper gastrointestinal tract, malabsorption
syndrome, or inability to take oral medication.
- Other severe acute or chronic medical or psychiatric condition, or significant
laboratory abnormality requiring further investigation or that may cause undue risk
for the patient's safety.
- Known human immunodeficiency virus (HIV) infection requiring treatment or acquired
immunodeficiency-syndrome (AIDS)-related illness.
- Patients who are pregnant or breastfeeding.