Brain Metastasis, Breast Cancer, Non Small Cell Lung Cancer
Conditions
Keywords
brain metastasis, breast cancer, HER2 negative, NSCLC
Brief 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
Detailed description
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.
Interventions
DRUGCabazitaxel
Intravenous, 25 mg/m2 every 3 weeks
PROCEDUREContrast-enhanced whole brain MRI
Evaluation of the volumetric reduction in the size of the brain lesion(s).
Sponsors
Sanofi
Jules Bordet Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction of brain lesions. | week 6 | Objective response defined as a \>= 50% volumetric reduction of brain lesions in the absence of increasing steroid use and progressive neurologic symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to whole brain irradiation or radiosurgery | every 6 weeks until disease progression. | Determine the effect of cabazitaxel on the time to initiating whole brain irradiation or radiosurgery |
| Time to developing neurological symptoms. | every 6 weeks until disease progression. | Determine the effect of cabazitaxel on the time to developing neurological symptoms |
| Time to progression in the brain | every 6 weeks until disease progression. | Determine the effect of cabazitaxel on the time to disease progression in the brain. |
| Time to progression extra-cranial | every 6 weeks until disease progression. | Determine the effect of cabazitaxel on the time to disease progression outside the brain |
| Toxicity | every 3 weeks until 30 days after last treatment administration. | Determine the safety of cabazitaxel |
Countries
Belgium
Outcome results
None listed