Clinical trial NCT00048633 (phase 2, status: completed)
Conditions: breast neoplasms
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: chemotherapy
SMILES: [H][C@@]12N(C)C3=CC(OC)=C(C=C3[C@@]11CCN3CC=C[C@](CC)([C@@]13[H])[C@@]([H])(OC(C)=O)[C@]2(O)C(=O)OC)[C@]1(C[C@@]2([H])CN(CC(CC)=C2)CC2=C1NC1=CC=CC=C21)C(=O)OC
Eligibility criteria:

        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.

        Exclusion criteria:

          -  More than 1 chemotherapy regimen for metastatic breast cancer.

          -  Patients who relapsed more than 6 months after completion of anthracycline or taxane
             therapy.

          -  Current treatment with a non-taxane, non-anthracycline based chemotherapy.

          -  Uncontrolled psychiatric, or social (addictive) disorders that would preclude
             obtaining informed consent or patient participation in the study.

          -  Clinical contraindication of continued anthracycline or taxane therapy. For patients
             who show primary resistance to anthracyclines this includes greater than 300 mg/m2
             maximum life-time cumulative dose of doxorubicin, symptomatic heart failure, history
             of heart failure, recent myocardial infarction (less than 6 months) or left
             ventricular ejection fraction below normal range. For patients with primary resistance
             to taxanes, persistent grade 2 or greater neuropathy (neuropathy that interferes with
             function).

          -  Patients with operable primary breast cancer are not eligible.

          -  Patients who have developed primary resistance to the chemotherapy combination of
             doxorubicin/docetaxel.