evaluation of cabazitaxel in patients with brain metastasis secondary to breast cancer and nsclc

Conditions: Brain Metastasis; Breast Cancer; Non Small Cell Lung Cancer

Summary: a phase ii trial evaluating cabazitaxel in patients with brain metastasis secondary to breast and non-small-cell lung cancer (nsclc). objectives: primary: the purpose of this study is to determine if cabazitaxel can induce a reduction in the size brain metastasis in metastatic her2-negative breast cancer and nsclc with brain metastasis who were not previously treated with whole brain irradiation or require immediate brain irradiation. secondary: * to determine the effect of cabazitaxel on the time to initiating whole brain irradiation or radiosurgery * to determine the effect of cabazitaxel on the time to developing neurological symptoms * to determine the effect of cabazitaxel on the time to disease progression in the brain * to determine the effect of cabazitaxel on the time to disease progression outside the brain. this will be evaluated separately for the breast and nsclc cohorts to determine the objective extra-cranial response (if applicable). this will be evaluated separately in the breast and nsclc cohorts * to determine the safety of cabazitaxel

this is a single arm, prospective trial using a 2-stage simon design, in which eligible patients will receive intravenous cabazitaxel for two cycles followed by response evaluation. based on the pre-specified criteria of response (intra-cranial, patient will be allowed to continue on study drug.

Eligibility criteria:
inclusion criteria: * signed informed consent * age\>18, ecog 0-1 * histologically confirmed 1) her2-negative invasive breast carcinoma or 2) nsclc * in patients with breast cancer, her2-negative status by fish or immunohistochemistry (score 0, or +1). * in patients with breast cancer, known estrogen and progesterone receptor status. * evidence of measurable disease in the brain (at least 1cm) * stable or decreasing dosage of steroids for 7 days prior to baseline mri. * no evidence of (cortical) cognitive impairment as defined by a mini-mental status exam (mmse) score ≥ 25/30. * no more than 4 prior lines of systemic chemotherapy in the metastatic setting * adequate hematopoietic function defined as: * hemoglobin ≥ 9.0g/dl * absolute neutrophilic count ≥ 1.5 x 109l * platelet count ≥ 100 x 109l * adequate hepatic function defined as: * ast ≤ 2.5 x upper limit of normal (uln) * alt ≤ 2.5 x uln * total bilirubin ≤ 1.0 x uln * adequate renal function defined as serum creatinine ≤ 1.5 x uln. if creatinine ranges from 1.0 - 1.5 x uln, creatinine clearance determined by ckd-epi formula should be calculated and only patients with clearance \>60 ml/min are eligible * adequate contraceptive method in patients with child-bearing potential. exclusion criteria: * history of prior whole brain irradiation * progressive neurological symptoms requiring immediate brain irradiation * pregnancy or lactation * history of hypersensitivity reaction to taxanes * history of hypersensitivity to polysorbate 80 containing agents * current or planned treatment with strong inhibitors or inducers of cytochrome p450. * less than 3 weeks since the last treatment of chemotherapy, biological therapy, and/or immunotherapy * leptomeningeal carcinomatosis * contra-indication to contrast-enhanced mri

Keywords: brain metastasis breast cancer her2 negative nsclc