Evaluation of Cabazitaxel in Patients With Brain Metastasis Secondary to Breast Cancer and NSCLC

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