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

A Phase II Evaluating Cabazitaxel in Patients With Brain Metastasis Secondary to Breast and Non-small Cell Lung Cancer

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

Study Overview

• Status: Withdrawn
• Conditions: Breast Cancer; Non Small Cell Lung Cancer; Brain Metastasis
• Intervention / Treatment: Drug: Cabazitaxel; Procedure: Contrast-enhanced whole brain MRI

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • Institut Jules Bordet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: Cabazitaxel; Intravenous, 25 mg/m2 every 3 weeks; Other Names: Jevtana; Procedure: Contrast-enhanced whole brain MRI; Evaluation of the volumetric reduction in the size of the brain lesion(s).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of brain lesions.	Objective response defined as a >= 50% volumetric reduction of brain lesions in the absence of increasing steroid use and progressive neurologic symptoms.	week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to whole brain irradiation or radiosurgery	Determine the effect of cabazitaxel on the time to initiating whole brain irradiation or radiosurgery	every 6 weeks until disease progression.
Time to developing neurological symptoms.	Determine the effect of cabazitaxel on the time to developing neurological symptoms	every 6 weeks until disease progression.
Time to progression in the brain	Determine the effect of cabazitaxel on the time to disease progression in the brain.	every 6 weeks until disease progression.
Time to progression extra-cranial	Determine the effect of cabazitaxel on the time to disease progression outside the brain	every 6 weeks until disease progression.
Toxicity	Determine the safety of cabazitaxel	every 3 weeks until 30 days after last treatment administration.

Collaborators and Investigators

• Sponsor: Jules Bordet Institute
• Collaborators: Sanofi
• Investigators: Principal Investigator: Ahmad Awada, MD, PhD, Institute Jules Bordet

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Anticipated): May 1, 2016
• Study Completion (Anticipated): September 1, 2016

Study Registration Dates

• First Submitted: July 18, 2013
• First Submitted That Met QC Criteria: July 29, 2013
• First Posted (Estimate): July 31, 2013

Study Record Updates

• Last Update Posted (Estimate): July 24, 2014
• Last Update Submitted That Met QC Criteria: July 23, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: breast cancer; NSCLC; HER2 negative; brain metastasis
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Breast Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Breast Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: CE2100; 2012-005194-32 (EudraCT Number)