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Phase 3 N=554 Randomized Double-blind Supportive Care

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

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

OutcomeResultp-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
View full record on ClinicalTrials.gov →

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.

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