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

Primary Purpose

Brain Metastasis, Breast Cancer, Non Small Cell Lung Cancer

Status
Withdrawn
Phase
Phase 2
Locations
Belgium
Study Type
Interventional
Intervention
Cabazitaxel
Contrast-enhanced whole brain MRI
Sponsored by
Jules Bordet Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain Metastasis focused on measuring brain metastasis, breast cancer, HER2 negative, NSCLC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Institut Jules Bordet

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cabazitaxel

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Time to whole brain irradiation or radiosurgery
Determine the effect of cabazitaxel on the time to initiating whole brain irradiation or radiosurgery
Time to developing neurological symptoms.
Determine the effect of cabazitaxel on the time to developing neurological symptoms
Time to progression in the brain
Determine the effect of cabazitaxel on the time to disease progression in the brain.
Time to progression extra-cranial
Determine the effect of cabazitaxel on the time to disease progression outside the brain
Toxicity
Determine the safety of cabazitaxel

Full Information

First Posted
July 18, 2013
Last Updated
July 23, 2014
Sponsor
Jules Bordet Institute
Collaborators
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT01913067
Brief Title
Evaluation of Cabazitaxel in Patients With Brain Metastasis Secondary to Breast Cancer and NSCLC
Acronym
CRANIAL
Official Title
A Phase II Evaluating Cabazitaxel in Patients With Brain Metastasis Secondary to Breast and Non-small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
July 2014
Overall Recruitment Status
Withdrawn
Why Stopped
Scientific rationale is deemed obsolete. Funders lost interest in the trial.
Study Start Date
September 2013 (undefined)
Primary Completion Date
May 2016 (Anticipated)
Study Completion Date
September 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jules Bordet Institute
Collaborators
Sanofi

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Metastasis, Breast Cancer, Non Small Cell Lung Cancer
Keywords
brain metastasis, breast cancer, HER2 negative, NSCLC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cabazitaxel
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Cabazitaxel
Other Intervention Name(s)
Jevtana
Intervention Description
Intravenous, 25 mg/m2 every 3 weeks
Intervention Type
Procedure
Intervention Name(s)
Contrast-enhanced whole brain MRI
Intervention Description
Evaluation of the volumetric reduction in the size of the brain lesion(s).
Primary Outcome Measure Information:
Title
Reduction of brain lesions.
Description
Objective response defined as a >= 50% volumetric reduction of brain lesions in the absence of increasing steroid use and progressive neurologic symptoms.
Time Frame
week 6
Secondary Outcome Measure Information:
Title
Time to whole brain irradiation or radiosurgery
Description
Determine the effect of cabazitaxel on the time to initiating whole brain irradiation or radiosurgery
Time Frame
every 6 weeks until disease progression.
Title
Time to developing neurological symptoms.
Description
Determine the effect of cabazitaxel on the time to developing neurological symptoms
Time Frame
every 6 weeks until disease progression.
Title
Time to progression in the brain
Description
Determine the effect of cabazitaxel on the time to disease progression in the brain.
Time Frame
every 6 weeks until disease progression.
Title
Time to progression extra-cranial
Description
Determine the effect of cabazitaxel on the time to disease progression outside the brain
Time Frame
every 6 weeks until disease progression.
Title
Toxicity
Description
Determine the safety of cabazitaxel
Time Frame
every 3 weeks until 30 days after last treatment administration.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ahmad Awada, MD, PhD
Organizational Affiliation
Institute Jules Bordet
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institut Jules Bordet
City
Brussels
ZIP/Postal Code
1000
Country
Belgium

12. IPD Sharing Statement

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

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