Phase 3
N=554
Memantine in Preventing Side Effects in Patients Undergoing Whole-Brain Radiation Therapy for Brain Metastases From Solid Tumors
Cognitive/Functional Effects · Metastatic Cancer · Neurotoxicity · Unspecified Adult Solid Tumor, Protocol Specific
Bottom Line
View on ClinicalTrials.gov: NCT00566852 ↗Enrolled (actual)
554
Serious AEs
29.6%
Results posted
Jul 2017
Primary outcome: Primary: Change in the Hopkins Verbal Learning Test - Revised for Delayed Recall (HVLT-R-delayed Recall) at 24 Weeks — 0; -0.9 units on a scale — p=0.059
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Memantine (Drug); Placebo (Other); Whole brain radiation therapy (Radiation)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Radiation Therapy Oncology Group
- Primary completion
- Apr 2011
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in the Hopkins Verbal Learning Test - Revised for Delayed Recall (HVLT-R-delayed Recall) at 24 Weeks |
0; -0.9 | 0.059 |
| SECONDARY Change in the Hopkins Verbal Learning Test - Revised for Delayed Recall (HVLT-R-delayed Recall) at 8, 16, and 52 Weeks |
-0.36; -0.72; 0; 0; 0; 0 | 0.0692 |
| SECONDARY Median Time to Neurocognitive Failure |
2.6; 2.3 | 0.01 sig |
| SECONDARY Change in Functional Assessment of Cancer Therapy With Brain Subscale (FACT-Br) at 24 Weeks |
0; 1 | 0.77 |
| SECONDARY Median Progression-free Survival Time |
4.7; 5.5 | 0.27 |
| SECONDARY Overall Survival |
6.7; 7.8 | 0.025 sig |
Summary
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.
Eligibility Criteria
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
- Blood urea nitrogen (BUN) < 20 mg/dL
- Mini-mental status exam score ≥ 18
- Negative serum pregnancy test
- Fertile patients must practice adequate contraception
Exclusion
- Severe, active co-morbidity, defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
- Transmural myocardial infarction within the last 6 months
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
- Pregnant or lactating women
- Prior allergic reaction to memantine hydrochloride
- Current alcohol or drug abuse
- Intractable seizures while on adequate anticonvulsant therapy (i.e., more than one seizure per month for the past 2 months)
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
- Prior cranial radiotherapy
- Patients may have received up to 3 prior WBRT treatments and still be registered and randomized on the protocol provided WBRT parameters meet protocol requirements
- Chronic short-acting benzodiazepine use
Data sourced from ClinicalTrials.gov (NCT00566852). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.