Clinical trial NCT01913067: Evaluation of Cabazitaxel in Patients With Brain Metastasis Secondary to Breast Cancer and NSCLC
Official title: A Phase II Evaluating Cabazitaxel in Patients With Brain Metastasis Secondary to Breast and Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Brain Metastasis
Breast Cancer
Non Small Cell Lung Cancer
Keywords: brain metastasis
breast cancer
HER2 negative
NSCLC
Lead sponsor: Jules Bordet Institute
Sponsor class: OTHER
Collaborators: name: Sanofi
First posted: 2013-07-31
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Reduction of brain lesions.
timeFrame: week 6
Secondary outcomes:
measure: Time to whole brain irradiation or radiosurgery
timeFrame: every 6 weeks until disease progression.
measure: Time to developing neurological symptoms.
timeFrame: every 6 weeks until disease progression.
measure: Time to progression in the brain
timeFrame: every 6 weeks until disease progression.
measure: Time to progression extra-cranial
timeFrame: every 6 weeks until disease progression.
measure: Toxicity
timeFrame: every 3 weeks until 30 days after last treatment administration.
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Institut Jules Bordet
Study officials:
affiliation: Institute Jules Bordet
name: Ahmad Awada, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: