December 1, 2007 |
May 13, 2009 |
March 2008 |
Cognitive function, specifically memory, 24 weeks from the start of drug treatment as measured by the Hopkins Verbal Learning Test-Revised for delayed
recall (HVLT-R-delayed recall) [ Designated as safety issue: No ] |
Same as current |
Complete list of historical versions of study NCT00566852 on ClinicalTrials.gov Archive Site |
- Cognitive function, specifically memory, 8 weeks, 16 weeks, and 12 months from the start of treatment as measured by the HVLT-R-delayed recall [ Designated as safety issue: No ]
- Neurocognitive failure as measured by a battery of tests [ Designated as safety issue: No ]
- Quality-of-life as measured by the Functional Assessment of Cancer Therapy Brain subscale (FACT-Br) [ Designated as safety issue: No ]
- Progression-free survival [ Designated as safety issue: No ]
- Overall survival [ Designated as safety issue: No ]
- Adverse events based on CTCAE 3.0 [ Designated as safety issue: Yes ]
- Collection of serum, plasma, buffy coat cells, urine, and cerebrospinal fluid for future translational research analyses [ Designated as safety issue: No ]
|
- Neurocognitive failure as measured by a battery of tests
- Quality-of-life as measured by the Functional Assessment of Cancer Therapy Brain subscale (FACT-Br)
- Progression-free survival
- Decline in cognitive function, specifically memory, from baseline to 8 weeks, 16 weeks, and 12 months from the start of treatment as measured by
the HVLT-delayed recall
|
|
Memantine in Preventing Side Effects in Patients Undergoing Whole-Brain Radiation Therapy for Brain Metastases From Solid Tumors |
A Randomized, Phase III, Double-Blind, Placebo-Controlled Trial of Memantine for Prevention of Cognitive Dysfunction in Patients Receiving Whole-Brain Radiotherapy |
RATIONALE: Memantine may be able to decrease side effects caused by whole-brain radiation therapy. It is not yet known if memantine is effective in preventing side effects caused by whole-brain radiation therapy.
PURPOSE: This randomized phase III trial is studying memantine to see how well it works compared to a placebo in preventing side effects caused by whole-brain radiation therapy in patients with brain metastases from solid tumors. |
OBJECTIVES:
Primary
- Determine whether the addition of memantine hydrochloride to whole-brain radiotherapy (WBRT) preserves cognitive function, specifically memory, as measured by the Hopkins Verbal Learning Test for delayed recall (HVLT-delayed recall), over that of placebo and WBRT in patients with brain metastases at 24 weeks from the start of drug treatment.
Secondary
- Determine whether the addition of memantine hydrochloride preserves cognitive function, specifically memory, as measured by the HVLT-delayed recall at 8 weeks, 16 weeks, and 12 months from the start of drug treatment.
- Determine whether the addition of memantine hydrochloride increases time to neurocognitive failure as measured by cognitive decline on a battery of tests including the HVLT for free recall, delayed recall, and delayed recognition; the Controlled Word Association Test (COWAT); the Trail Making Test Parts A and B (TMT); the Medical Outcomes Scale-Cognitive Functioning Subscale (MOS); and the Mini-Mental Status Examination (MMSE).
- Evaluate the potential benefit of memantine hydrochloride in change and overall quality of life, as measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) subscale.
- Determine whether the addition of memantine hydrochloride increases progression-free survival.
- Determine whether the addition of memantine hydrochloride increases overall survival.
- Compare adverse events between the treatment arms according to the CTCAE v3.0 criteria.
- Collect serum, plasma, buffy coat cells, urine, and CSF for future translational research analyses.
OUTLINE: This is a multicenter study. Patients are stratified according to recursive partitioning analysis (RPA) prognostic class (class I vs class II with controlled systemic disease) and prior surgical therapy (none vs radiosurgery or surgical resection). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients undergo whole-brain radiotherapy (WBRT) 5 days a week for 3 weeks (15 fractions). Patients also receive oral memantine hydrochloride once daily beginning on day 1 of WBRT and continuing for 24 weeks.
- Arm II: Patients undergo WBRT as in arm I. Patients also receive oral placebo once daily beginning on day 1 of WBRT and continuing for 24 weeks. After completion of study treatment, patients are followed at 6 months, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.
|
Phase III |
Interventional |
Supportive Care, Randomized, Double-Blind, Placebo Control |
- Brain and Central Nervous System Tumors
- Cognitive/Functional Effects
- Neurotoxicity
- Unspecified Adult Solid Tumor, Protocol Specific
|
- Drug: memantine hydrochloride
- Other: placebo
- Radiation: radiation therapy
|
- Experimental: Patients undergo whole-brain radiotherapy (WBRT) 5 days a week for 3 weeks (15 fractions). Patients also receive oral memantine hydrochloride once daily beginning on day 1 of WBRT and continuing for 24 weeks.
- Active Comparator: Patients undergo WBRT as in arm I. Patients also receive oral placebo once daily beginning on day 1 of WBRT and continuing for 24 weeks.
|
|
|
Recruiting |
536 |
|
June 2012 (final data collection date for primary outcome measure) |
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed diagnosis of a solid tumor malignancy within the past 5 years
- If the original histologic proof of malignancy is > 5 years, then pathological (i.e., more recent) confirmation is required (e.g., from a systemic metastasis or brain metastasis)
Brain metastases must be visible on contrast-enhanced MRI or a contrast enhanced CT scan (for patients unable to undergo MRI within the past 28 days)
- Patients unable to undergo MRI imaging because of non-compatible devices are eligible, provided the contrast-enhanced CT scans are obtained and are of sufficient quality
- Patients who had undergone radiosurgery or surgical resection and are planning adjuvant whole-brain radiotherapy do not have to have visible disease but do need a baseline MRI
- Must have stable systemic disease (i.e. no evidence of systemic disease progression within the past 3 months)
- Patients with brain metastases at initial presentation are eligible and do not need to demonstrate 3 months of stable scans
PATIENT CHARACTERISTICS:
Inclusion
- Karnofsky performance status 70-100%
- Serum creatinine ≤ 3 mg/dL and creatinine clearance ≥ 30 mL/min
- Total bilirubin ≤ 2.5 mg/dL
- BUN < 20 mg/dL
- Mini-mental status exam score ≥ 18
- Negative serum pregnancy test
- Fertile patients must practice adequate contraception
Exclusion
PRIOR CONCURRENT THERAPY:
Inclusion
- At least 14 days but no more than 56 days since prior therapy for brain metastasis, including radiosurgery and surgical resection
- No systemic chemotherapy for 14 days prior, during, or for 14 days after completion of whole-brain radiotherapy (WBRT)
Exclusion
|
Both |
18 Years and older |
No |
|
United States, Canada |
|
|
NCT00566852 |
Walter John Curran, Jr, Radiation Therapy Oncology Group |
RTOG-0614 |
Radiation Therapy Oncology Group |
National Cancer Institute (NCI) |
Study Chair: |
Paul D. Brown, MD |
Mayo Clinic |
|
Investigator: |
Christina A. Meyers, PhD |
M.D. Anderson Cancer Center |
|
Investigator: |
Sherry Fox, RN, PhD |
Bon Secours Cancer Institute at St. Mary's Hospital |
|
Investigator: |
Deepak Khuntia, MD |
University of Wisconsin, Madison |
|
|
National Cancer Institute (NCI) |
May 2009 |