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

NCT ID: NCT01913067

Last Updated: 2014-07-24

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2016-09-30

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.

Conditions

Brain Metastasis; Breast Cancer; Non Small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cabazitaxel

Eligible patients will receive intravenous 25mg/m2 cabazitaxel every 3 weeks. Contrast-enhanced whole brain MRI will be performed every two cycles. Patients who show ≥50% volumetric reduction in the size of the brain lesion(s) will continue on cabazitaxel until disease progression or unacceptable toxicity. Patients who show evidence of disease progression and/or developed progressive neurological symptoms will be taken off study and offered whole brain irradiation. Patients who do not meet both criteria can have the choice either to continue on study drug or to be taken off study according to the investigator discretion.

Group Type: EXPERIMENTAL

Cabazitaxel

Intervention Type: DRUG

Intravenous, 25 mg/m2 every 3 weeks

Contrast-enhanced whole brain MRI

Intervention Type: PROCEDURE

Evaluation of the volumetric reduction in the size of the brain lesion(s).

Interventions

Cabazitaxel

Intravenous, 25 mg/m2 every 3 weeks

Intervention Type: DRUG

Contrast-enhanced whole brain MRI

Evaluation of the volumetric reduction in the size of the brain lesion(s).

Intervention Type: PROCEDURE

Other Intervention Names

Jevtana

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

Jules Bordet Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ahmad Awada, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Institute Jules Bordet

Locations

Institut Jules Bordet

Brussels, Brussels Capital, Belgium

Countries

Belgium

Other Identifiers

2012-005194-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CE2100

Identifier Type: -

Identifier Source: org_study_id