A Randomized, Phase III, Double-Blind, Placebo-Controlled Trial of Memantine for Prevention of Cognitive Dysfunction in Patients Receiving Whole-Brain Radiotherapy
Investigator:
Young Kwok, M.D.
Summary:
2.1 Primary Objective
Determine whether the addition of memantine to WBRT preserves cognitive function, specifically memory as measured by the Hopkins Verbal Learning Test-Revised for delayed recall (HVLT-R delayed recall), over that of placebo and WBRT in patients with brain metastases at 24 weeks from the start of drug treatment.
2.2. Secondary Objectives
2.2.1 Determine whether the addition of memantine preserves cognitive function, specifically memory as measured by the HVLT-R-delayed recall at 8 weeks, 16 weeks and 12 months from the start of drug treatment.
2.2.2 Determine whether the addition of memantine increases time to neurocognitive failure as measured by cognitive decline on a battery of tests: the HVLT-R for free recall, delayed recall, and delayedrecognition; 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). (3/28/08)
2.2.3 Evaluate the potential benefit of memantine in change and overall quality of life, as measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br).
2.2.4 Determine whether the addition of memantine increases progression-free survival.
2.2.5 Determine whether the addition of memantine increases overall survival.
2.2.6 Compare adverse events between the treatment arms according to the CTCAE v3.0 criteria.
2.2.7 Collect serum, plasma, buffy coat cells, urine, and CSF for future translational research analyses
Disease site:
Central Nervous System
Disease stage:
Pathologically proven solid tumor malignancy and brain metastases.
Condition:
Solid tumor malignancy and brain metastases.
Intervention:
Drug/Placebo + Radiation Therapy
Phase:
III
Study number:
RTOG 0614
Eligibility*
(inclusion criteria)
3.1.1 Pathologically (histologically or cytologically) proven diagnosis of solid tumor malignancy within 5 years of registration. If the original histologic proof of malignancy is greater than 5 years, then pathological (i.e., more recent) confirmation is required (e.g., from a systemic metastasis or brain metastasis).
3.1.2 Brain metastases must be visible on contrast-enhanced MRI or a contrast enhanced CT for patients unable to have an MRI performed d28 days prior to study entry (an allowed exception, regarding ability to image brain metastases, would be patients who had undergone radiosurgery or surgical resection and are planning adjuvant WBRT do not have to have visible disease but do need a baseline MRI). Patients unable to undergo MR imaging because of non-compatible devices can be enrolled, provided the contrast-enhanced CT scans are obtained and are of sufficient quality.
3.1.3 Patients must have stable systemic disease (i.e. no evidence of systemic disease progression e3 months prior to study entry). Patients who have brain metastases at initial presentation are eligible and do not need to demonstrate 3 months of stable scans.
3.1.4 Karnofsky Performance Status of e70 within 28 days prior to study entry.
3.1.5 Age e 18
3.1.6 Serum creatinine and total bilirubin obtained d28 days prior to study entry; with adequate kidney and liver function defined as follows:
a. Serum creatinine d 3 mg/dL (265 ¼mol/L) and creatinine clearance e30 ml/min;
b. Total bilirubin d 2.5 mg/dL (43 ¼mol/L)
3.1.7 BUN < 20 mg/dL d28 days prior to study entry.
3.1.8 MMSE score >18 within 28 days prior to study entry.
3.1.9 Patient must provide study specific informed consent prior to study entry.
3.1.10 Patients may have had prior therapy for brain metastasis, including radiosurgery and surgical resection. Patients should have completed prior therapy at least 14 days but no longer than 56 days prior to study entry.
3.1.11 Patients receiving systemic therapy are eligible for this study if given >14 days prior to study entry and given no sooner than >14 days post RT completion.
3.1.12 Negative serum pregnancy test (in women of childbearing potential) d7 days prior to study entry.
3.1.13 Women of childbearing potential and men who are sexually active must practice adequate contraception.
3.1.14 Complete history and general physical examination d 28 days prior to study entry.
(exclusion criteria)
3.2.1 Uncontrolled systemic disease (evidence of systemic disease progression within 3 months or more)
3.2.2 Systemic chemotherapy d14 days prior to study entry or d14 days after completing radiotherapy 3.2.3 Prior cranial radiotherapy (a patient may have already received up to 3 WBRT treatments and still be registered and randomized on the protocol as long as WBRT parameters meet protocol requirements). As noted above, prior radiosurgery is allowed.
3.2.4 Severe, active co-morbidity, defined as follows:
3.2.4.1 Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
3.2.4.2 Transmural myocardial infarction within the last 6 months
3.2.4.3 Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
3.2.4.4 Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
3.2.4.5 Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
3.2.5 Pregnant or lactating women, or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the medication involved in this study has unknown effects on the unborn fetus.
3.2.6 Prior allergic reaction to memantine.
3.2.7 Current alcohol or drug abuse (may exacerbate lethargy/dizziness with memantine).
3.2.8 Chronic short-acting benzodiazepine use (may exacerbate lethargy/dizziness with memantine).
3.2.9 Intractable seizures while on adequate anticonvulsant therapy more than one seizure per month for the past 2 months.
Contact Person
Ritesh Kataria, MS 410-328-8018
* Note: This study may include eligibility criteria that are not listed here. For more information about the study or to find out if you are eligible, call 1-800-888-8823.
Email this Page
Print this Page
