Exploratory Study, Evaluating the Treatment Effect of Surgery Plus GLIADEL® Wafer in Patients With Metastatic Brain Cancer

Metastatic Brain Cancer Clinical Trial

Official title:

A Phase 2, Multicenter, Exploratory Study, Evaluating the Treatment Effect of Surgery Plus GLIADEL® Wafer in Patients With Metastatic Brain Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00525590
• Other study ID #: GLIA-001
• Status: Completed
• Phase: Phase 2
• Start date: December 12, 2007
• Est. completion date: December 1, 2010

Study information

• Verified date: February 2020
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: December 1, 2010
• Est. primary completion date: December 1, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Can provide signed/dated Informed Consent, and Health Insurance Portability and Accountability Act of 1996 (HIPAA) authorization.

2. Are a male or female patient 18 years of age or older.

3. 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.

4. 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.

5. Have a life expectancy of =12 weeks.

6. Have a Karnofsky Performance Status (KPS) score of 70 or higher.

7. Have Recursive Partitioning Analysis (RPA) status of 1 or 2.

8. Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days of the surgical resection; and

9. 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:

1. Are unable or unwilling to understand study assessment or to cooperate with the study procedures as determined by the investigator.

2. Have a history of allergic reaction or known hypersensitivity to BCNU (carmustine) or other components of the GLIADEL, such as polifeprosan polymer.

3. Have a history of prior cranial irradiation.

4. Have a prior diagnosis of Central Nervous System (CNS) tumor.

5. Have received prior treatment for brain tumors.

6. Have had prior exposure to GLIADEL or its components, such as polifeprosan polymer.

7. Have any uncontrolled medical or psychiatric conditions which preclude them from participating in or completing the study procedures.

8. 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.

9. Have a diagnosis of tumor in the brain stem or posterior fossa.

10. Have an RPA status of 3.

11. Have a diagnosis of leptomeningeal disease at time of enrollment; or

12. Are currently pregnant or lactating, or plan to become pregnant during the course of the study.

Related Conditions & MeSH terms

• Brain Neoplasms
• Metastatic Brain Cancer

Intervention

Drug:
• GLIADEL
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.

Locations

Country	Name	City	State
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Carolina Neurosurgery & Spine Associates	Charlotte	North Carolina
United States	The University of Chicago	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	The Ohio State University Medical Center	Columbus	Ohio
United States	UT Southwestern Medical Center at Dallas	Dallas	Texas
United States	NorthShore University HealthSystem Reseach Institute	Evanston	Illinois
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of California, Los Angeles	Los Angeles	California
United States	Methodist University Hospital	Memphis	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Weill Medical College Department of Neurological Surgery	New York	New York
United States	Temple University	Philadelphia	Pennsylvania
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida
United States	University of South Florida	Tampa	Florida
United States	University of Arizona / University Medical Center	Tucson	Arizona
United States	Trinity Mother Frances Health System	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Month 12
Primary	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).	Month 2
Primary	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).	Month 4
Primary	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).	Month 6
Primary	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).	Month 9
Primary	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).	Month 12
Secondary	Percentage of Participants With Brain Tumor Recurrence (Local Recurrence, Distant Recurrence and Overall Recurrence)		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)
Secondary	Time to Recurrence (Local, Distant and Overall)		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)
Secondary	Correlation of Tumor Recurrence With Residual Mass Effect		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)
Secondary	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.	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)
Secondary	Percentage of Participants With Neurologic Death	Neurologic Death was defined as death due to progression of neurologic disease.	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)
Secondary	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.	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)
Secondary	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.	Months 2, 4, 6, 9 and 12