Back to resultsExploratory Study, Evaluating the Treatment Effect of Surgery Plus GLIADEL® Wafer in Patients With Metastatic Brain Cancer
Primary Purpose
Metastatic Brain Cancer
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
GLIADEL
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Brain Cancer focused on measuring Gliadel
Eligibility Criteria
Inclusion Criteria:
- Can provide signed/dated Informed Consent, and Health Insurance Portability and Accountability Act of 1996 (HIPAA) authorization.
- Are a male or female patient 18 years of age or older.
- Are willing to a use barrier method of contraception if fertile or of childbearing potential until 30 days after surgical resection. If the patient receives subsequent chemotherapy during study participation (as allowed by the protocol), appropriate contraception will be managed by the principal investigator.
Have a primary diagnosis of solid-based tumor cancer (except small cell lung cancer (SCLS), lymphoma, germ cell cancer or anaplastic thyroid cancer) or unknown primary cancer and have 1-3 brain metastasis(es) for which surgical resection is planned for a single metastasis and any remaining metastases are planned for stereotactic radiosurgery (SRS);
OR
an intra-operative diagnosis of metastatic brain tumor in a patient with a single brain lesion.
- Have a life expectancy of ≥12 weeks.
- Have a Karnofsky Performance Status (KPS) score of 70 or higher.
- Have Recursive Partitioning Analysis (RPA) status of 1 or 2.
- Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days of the surgical resection; and
- Patients must be able to understand English, either orally or in writing, and be able to consent and complete the required assessments and procedures.
Exclusion Criteria:
- Are unable or unwilling to understand study assessment or to cooperate with the study procedures as determined by the investigator.
- Have a history of allergic reaction or known hypersensitivity to BCNU (carmustine) or other components of the GLIADEL, such as polifeprosan polymer.
- Have a history of prior cranial irradiation.
- Have a prior diagnosis of Central Nervous System (CNS) tumor.
- Have received prior treatment for brain tumors.
- Have had prior exposure to GLIADEL or its components, such as polifeprosan polymer.
- Have any uncontrolled medical or psychiatric conditions which preclude them from participating in or completing the study procedures.
- Concurrent severe medical conditions include, but are not limited to, active infection, acute hepatitis, cardiac arrhythmia, unstable angina, congestive heart failure, uncontrolled diabetes mellitus, uncontrolled seizures, pulmonary insufficiency, pulmonary fibrosis, pulmonary embolus, etc.
- Have a diagnosis of tumor in the brain stem or posterior fossa.
- Have an RPA status of 3.
- Have a diagnosis of leptomeningeal disease at time of enrollment; or
- Are currently pregnant or lactating, or plan to become pregnant during the course of the study.
Sites / Locations
- University of Arizona / University Medical Center
- University of California, Los Angeles
- University of South Florida
- H. Lee Moffitt Cancer Center & Research Institute
- The University of Chicago
- NorthShore University HealthSystem Reseach Institute
- University of Iowa Hospitals and Clinics
- Weill Medical College Department of Neurological Surgery
- University of North Carolina
- Carolina Neurosurgery & Spine Associates
- Cleveland Clinic
- The Ohio State University Medical Center
- Temple University
- Methodist University Hospital
- Vanderbilt University Medical Center
- UT Southwestern Medical Center at Dallas
- Trinity Mother Frances Health System
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
Outcomes
Primary Outcome Measures
Rate of Deterioration in Neurocognitive Functioning (NF) at Month 12
NF was assessed as the performance of 3 neurocognitive domains:memory(MD),executive function(EFD), fine motor coordination(FMCD). For each domain, z-scores were derived from participant's scores in individual neurocognitive tests using an age-adjusted and education-adjusted normative distribution of scores from an unimpaired population.Individual z-scores from related tests were averaged to determine overall z-score.If a z-score average decreased from baseline by greater than or equal to(>=)3 standard deviations(SD)in tests' normative age-adjusted distribution on 2 consecutive visits or decreased by >=3 SD on last follow-up visit, participant were considered to have significant deterioration in their NF at time of the first decrease in z-score.Deterioration in NF:demonstrated deterioration for at least two of the three neurocognitive domains based on these changes from screening.Rate of deterioration in NF was measured as estimated percentage of participants using Kaplan-Meier method.
Number of Participants With Neurocognitive Domains Preserved at Month 2
Preservation of NF was defined as a decrease of <=1 SD, any increase, or no change (0 SD) in z-score for each domain (memory domain, executive function domain, and fine motor coordination domain).
Number of Participants With Neurocognitive Domains Preserved at Month 4
Preservation of NF was defined as a decrease of <=1 SD, any increase, or no change (0 SD) in z-score for each domain (memory domain, executive function domain, and fine motor coordination domain).
Number of Participants With Neurocognitive Domains Preserved at Month 6
Preservation of NF was defined as a decrease of <=1 SD, any increase, or no change (0 SD) in z-score for each domain (memory domain, executive function domain, and fine motor coordination domain).
Number of Participants With Neurocognitive Domains Preserved at Month 9
Preservation of NF was defined as a decrease of <=1 SD, any increase, or no change (0 SD) in z-score for each domain (memory domain, executive function domain, and fine motor coordination domain).
Number of Participants With Neurocognitive Domains Preserved at Month 12
Preservation of NF was defined as a decrease of less than or equal to (<=) 1 SD, any increase, or no change (0 SD) in z-score for each domain (memory domain, executive function domain, and fine motor coordination domain).
Secondary Outcome Measures
Percentage of Participants With Brain Tumor Recurrence (Local Recurrence, Distant Recurrence and Overall Recurrence)
Time to Recurrence (Local, Distant and Overall)
Correlation of Tumor Recurrence With Residual Mass Effect
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores
The correlation between recurrence (local, distant or overall) & NF was assessed by presenting change in NF domain scores (memory domain [MD], executive function domain [EFD], fine motor coordination domain [FMCD]) after tumor recurrence (Visits X, X+1, X+2, and X+3) compared to before tumor recurrence (Visit X-1). Here 'Visit X' refers to visit at which participants had tumor recurrence, Visit X-1 refers to visit immediately before the recurrence and X+1, X+2, X+3 refers to subsequent first, second & third visit after the recurrence.NF domain z-scores were derived from participant's scores in individual neurocognitive tests using an age-adjusted &education-adjusted normative distribution of scores from an unimpaired population. Individual z-scores from related tests were averaged to determine overall z-score for each of NF domains.
Percentage of Participants With Neurologic Death
Neurologic Death was defined as death due to progression of neurologic disease.
Time to Neurocognitive Deterioration
The time to neurocognitive deterioration was defined as the number of days between the date of study treatment and the date of neurocognitive deterioration based on NF assessment. This was assessed using Kaplan Meier method.
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain)
Neurocognitive decline was defined as any decrease in NF scores less than (<) 0 SD from baseline. Here, in category titles EFD represents Executive Function Domain and FMCD represents Fine Motor Coordination Domain.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00525590
Brief Title
Exploratory Study, Evaluating the Treatment Effect of Surgery Plus GLIADEL® Wafer in Patients With Metastatic Brain Cancer
Official Title
A Phase 2, Multicenter, Exploratory Study, Evaluating the Treatment Effect of Surgery Plus GLIADEL® Wafer in Patients With Metastatic Brain Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
December 12, 2007 (Actual)
Primary Completion Date
December 1, 2010 (Actual)
Study Completion Date
December 1, 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eisai Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine the effect of the surgical intervention and insertion of GLIADEL wafers on the neurocognitive functioning in patients with metastatic brain cancer.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Brain Cancer
Keywords
Gliadel
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
69 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
GLIADEL
Intervention Description
Resect the tumor as completely as possible. After repeated irrigation of the decompressed area demonstrates no bleeding, and care is taken not to have any foreign material enter the ventricle, up to 8 GLIADEL wafers should be placed to cover the entire surface area of the resection cavity (if possible). Slight overlapping of wafer edges is permitted. The number of wafers will be determined by the size of the tumor resection cavity. Each GLIADEL wafer contains 7.7 mg of carmustine, resulting in a dose of 61.6 mg when 8 wafers are implanted. The GLIADEL wafer is a round white to yellow disk with flat surfaces.
Primary Outcome Measure Information:
Title
Rate of Deterioration in Neurocognitive Functioning (NF) at Month 12
Description
NF was assessed as the performance of 3 neurocognitive domains:memory(MD),executive function(EFD), fine motor coordination(FMCD). For each domain, z-scores were derived from participant's scores in individual neurocognitive tests using an age-adjusted and education-adjusted normative distribution of scores from an unimpaired population.Individual z-scores from related tests were averaged to determine overall z-score.If a z-score average decreased from baseline by greater than or equal to(>=)3 standard deviations(SD)in tests' normative age-adjusted distribution on 2 consecutive visits or decreased by >=3 SD on last follow-up visit, participant were considered to have significant deterioration in their NF at time of the first decrease in z-score.Deterioration in NF:demonstrated deterioration for at least two of the three neurocognitive domains based on these changes from screening.Rate of deterioration in NF was measured as estimated percentage of participants using Kaplan-Meier method.
Time Frame
Month 12
Title
Number of Participants With Neurocognitive Domains Preserved at Month 2
Description
Preservation of NF was defined as a decrease of <=1 SD, any increase, or no change (0 SD) in z-score for each domain (memory domain, executive function domain, and fine motor coordination domain).
Time Frame
Month 2
Title
Number of Participants With Neurocognitive Domains Preserved at Month 4
Description
Preservation of NF was defined as a decrease of <=1 SD, any increase, or no change (0 SD) in z-score for each domain (memory domain, executive function domain, and fine motor coordination domain).
Time Frame
Month 4
Title
Number of Participants With Neurocognitive Domains Preserved at Month 6
Description
Preservation of NF was defined as a decrease of <=1 SD, any increase, or no change (0 SD) in z-score for each domain (memory domain, executive function domain, and fine motor coordination domain).
Time Frame
Month 6
Title
Number of Participants With Neurocognitive Domains Preserved at Month 9
Description
Preservation of NF was defined as a decrease of <=1 SD, any increase, or no change (0 SD) in z-score for each domain (memory domain, executive function domain, and fine motor coordination domain).
Time Frame
Month 9
Title
Number of Participants With Neurocognitive Domains Preserved at Month 12
Description
Preservation of NF was defined as a decrease of less than or equal to (<=) 1 SD, any increase, or no change (0 SD) in z-score for each domain (memory domain, executive function domain, and fine motor coordination domain).
Time Frame
Month 12
Secondary Outcome Measure Information:
Title
Percentage of Participants With Brain Tumor Recurrence (Local Recurrence, Distant Recurrence and Overall Recurrence)
Time Frame
Up to Month 12 (from baseline until evidence of neurological deterioration, had a local recurrence, withdrawn, died, lost to follow-up, or the study was closed)
Title
Time to Recurrence (Local, Distant and Overall)
Time Frame
Up to Month 12 (from baseline until evidence of neurological deterioration, had a local recurrence, withdrawn, died, lost to follow-up, or the study was closed)
Title
Correlation of Tumor Recurrence With Residual Mass Effect
Time Frame
Up to Month 12 (from baseline until evidence of neurological deterioration, had a local recurrence, withdrawn, died, lost to follow-up, or the study was closed)
Title
Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores
Description
The correlation between recurrence (local, distant or overall) & NF was assessed by presenting change in NF domain scores (memory domain [MD], executive function domain [EFD], fine motor coordination domain [FMCD]) after tumor recurrence (Visits X, X+1, X+2, and X+3) compared to before tumor recurrence (Visit X-1). Here 'Visit X' refers to visit at which participants had tumor recurrence, Visit X-1 refers to visit immediately before the recurrence and X+1, X+2, X+3 refers to subsequent first, second & third visit after the recurrence.NF domain z-scores were derived from participant's scores in individual neurocognitive tests using an age-adjusted &education-adjusted normative distribution of scores from an unimpaired population. Individual z-scores from related tests were averaged to determine overall z-score for each of NF domains.
Time Frame
Up to Month 12 (from baseline until evidence of neurological deterioration, had a local recurrence, withdrawn, died, lost to follow-up, or the study was closed)
Title
Percentage of Participants With Neurologic Death
Description
Neurologic Death was defined as death due to progression of neurologic disease.
Time Frame
Up to Month 12 (from baseline until evidence of neurological deterioration, had a local recurrence, withdrawn, died, lost to follow-up, or the study was closed)
Title
Time to Neurocognitive Deterioration
Description
The time to neurocognitive deterioration was defined as the number of days between the date of study treatment and the date of neurocognitive deterioration based on NF assessment. This was assessed using Kaplan Meier method.
Time Frame
Up to Month 12 (from baseline until evidence of neurological deterioration, had a local recurrence, withdrawn, died, lost to follow-up, or the study was closed)
Title
Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain)
Description
Neurocognitive decline was defined as any decrease in NF scores less than (<) 0 SD from baseline. Here, in category titles EFD represents Executive Function Domain and FMCD represents Fine Motor Coordination Domain.
Time Frame
Months 2, 4, 6, 9 and 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Can provide signed/dated Informed Consent, and Health Insurance Portability and Accountability Act of 1996 (HIPAA) authorization.
Are a male or female patient 18 years of age or older.
Are willing to a use barrier method of contraception if fertile or of childbearing potential until 30 days after surgical resection. If the patient receives subsequent chemotherapy during study participation (as allowed by the protocol), appropriate contraception will be managed by the principal investigator.
Have a primary diagnosis of solid-based tumor cancer (except small cell lung cancer (SCLS), lymphoma, germ cell cancer or anaplastic thyroid cancer) or unknown primary cancer and have 1-3 brain metastasis(es) for which surgical resection is planned for a single metastasis and any remaining metastases are planned for stereotactic radiosurgery (SRS);
OR
an intra-operative diagnosis of metastatic brain tumor in a patient with a single brain lesion.
Have a life expectancy of ≥12 weeks.
Have a Karnofsky Performance Status (KPS) score of 70 or higher.
Have Recursive Partitioning Analysis (RPA) status of 1 or 2.
Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days of the surgical resection; and
Patients must be able to understand English, either orally or in writing, and be able to consent and complete the required assessments and procedures.
Exclusion Criteria:
Are unable or unwilling to understand study assessment or to cooperate with the study procedures as determined by the investigator.
Have a history of allergic reaction or known hypersensitivity to BCNU (carmustine) or other components of the GLIADEL, such as polifeprosan polymer.
Have a history of prior cranial irradiation.
Have a prior diagnosis of Central Nervous System (CNS) tumor.
Have received prior treatment for brain tumors.
Have had prior exposure to GLIADEL or its components, such as polifeprosan polymer.
Have any uncontrolled medical or psychiatric conditions which preclude them from participating in or completing the study procedures.
Concurrent severe medical conditions include, but are not limited to, active infection, acute hepatitis, cardiac arrhythmia, unstable angina, congestive heart failure, uncontrolled diabetes mellitus, uncontrolled seizures, pulmonary insufficiency, pulmonary fibrosis, pulmonary embolus, etc.
Have a diagnosis of tumor in the brain stem or posterior fossa.
Have an RPA status of 3.
Have a diagnosis of leptomeningeal disease at time of enrollment; or
Are currently pregnant or lactating, or plan to become pregnant during the course of the study.
Facility Information:
Facility Name
University of Arizona / University Medical Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
University of California, Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
Facility Name
H. Lee Moffitt Cancer Center & Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
The University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
NorthShore University HealthSystem Reseach Institute
City
Evanston
State/Province
Illinois
ZIP/Postal Code
60201
Country
United States
Facility Name
University of Iowa Hospitals and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Weill Medical College Department of Neurological Surgery
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Carolina Neurosurgery & Spine Associates
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
The Ohio State University Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Temple University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
Facility Name
Methodist University Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38104
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
UT Southwestern Medical Center at Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Trinity Mother Frances Health System
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
24037801
Citation
Brem S, Meyers CA, Palmer G, Booth-Jones M, Jain S, Ewend MG. Preservation of neurocognitive function and local control of 1 to 3 brain metastases treated with surgery and carmustine wafers. Cancer. 2013 Nov 1;119(21):3830-8. doi: 10.1002/cncr.28307. Epub 2013 Aug 23.
Results Reference
derived
Learn more about this trial
Exploratory Study, Evaluating the Treatment Effect of Surgery Plus GLIADEL® Wafer in Patients With Metastatic Brain Cancer
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