Phase II Study to Evaluate Tariquidar (XR9576), a Selective MDR-1 Inhibitor, in Chemotherapy Resistant Advanced Breast Cancer

Inclusion Criteria

• •Histologically proven breast cancer with primary resistance to anthracyclines (doxorubicin, epirubicin) or taxane (paclitaxel, docetaxel) or both. Primary chemotherapy resistance is defined for the purpose of this protocol as any of the following:
• •1. Progression after a minimum of 1 cycles of therapy, or
• •2. Stable disease after a minimum of 2 cycles of therapy or,
• •3. Relapse within 6 months after completion of an anthracycline or/and taxane containing chemotherapy regimen.
• •Patients with anthracycline/taxane resistance INOPERABLE, locally advanced breast cancer are eligible.
• •Patients must have measurable disease as defined by the RECIST criteria in their breast/nodal regions or at a distant organ site(s).
• •There is no limit on prior hormonal therapies but only one prior chemotherapy for metastatic breast cancer is allowed.
• •Patients may receive concomitant bisphosphonate therapy for bone metastasis.
• •Patients may continue Herceptin if it has previously been started. Herceptin cannot be added to the chemotherapy regimen as a new agent at the same time when XR9576 is initiated.
• •Patients much have recovered from acute toxic effects of any prior therapy.
• •Zubrod performance status less than or equal to 2.
• •Adequate bone marrow function: platelets greater than or equal to 100,000/mm3, ANC greater than or equal to 1500 cells/mm3, hemoglobin greater than or equal to 8g/dl.
• •Normal renal function: creatinine less than or equal to 2.0 mg/dl. Adequate liver function: bilirubin less than or equal to 1.5 mg/dl. Transaminase (SGOT) and alkaline phosphatase must be less than or equal to 1.5 x of the upper limit of normal in the absence of bone or liver metastasis, or less than or equal to 2.5 x of the upper limit of normal in the presence of radiologically apparent liver metastasis or bone metastasis, respectively.
• •Female patients must be of non-lactating and using adequate contraception if premenopausal. Beta-HCG will be checked in premenopausal patients if clinically indicated.
• •Patients with brain metastases whose disease remained stable for more than 3 months after completing therapy to the brain are eligible.
• •Written informed consent.