Memantine in Preventing Side Effects in Patients Undergoing Whole-Brain Radiation Therapy for Brain Metastases From Solid Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00566852
First received: December 1, 2007
Last updated: December 20, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Cognitive/Functional Effects
Metastatic Cancer
Neurotoxicity
Unspecified Adult Solid Tumor, Protocol Specific
Drug: memantine hydrochloride
Other: placebo
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Supportive Care
Official Title: A Randomized, Phase III, Double-Blind, Placebo-Controlled Trial of Memantine for Prevention of Cognitive Dysfunction in Patients Receiving Whole-Brain Radiotherapy

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • 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) [ Time Frame: Baseline to 24 weeks from the start of drug treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cognitive function, specifically memory, 8 weeks, 16 weeks, and 12 months from the start of treatment as measured by the HVLT-R-delayed recall [ Time Frame: Baseline to 12 months from the start of drug treatment ] [ Designated as safety issue: No ]
  • Neurocognitive failure as measured by a battery of tests [ Time Frame: Baseline to 12 months from the start of drug treatment ] [ Designated as safety issue: No ]
  • Quality-of-life as measured by the Functional Assessment of Cancer Therapy Brain subscale (FACT-Br) [ Time Frame: Baseline to 12 months from the start of drug treatment ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: From randomization to date of progression, death or last follow-up. Analysis occurs at the same time as the primary outcome. ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: From randomization to date of death or last follow-up. Analysis occurs at the same time as the primary outcome. ] [ Designated as safety issue: No ]

Enrollment: 554
Study Start Date: March 2008
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: memantine hydrochloride
Given orally
Radiation: radiation therapy
Patients undergo whole-brain radiotherapy (WBRT) 5 days a week for 3 weeks.
Active Comparator: 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.
Other: placebo
Given orally
Radiation: radiation therapy
Patients undergo whole-brain radiotherapy (WBRT) 5 days a week for 3 weeks.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00566852

  Show 235 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
Investigators
Principal Investigator: Paul D. Brown, MD Mayo Clinic
Study Chair: Christina A. Meyers, PhD M.D. Anderson Cancer Center
Study Chair: Sherry Fox, RN, PhD Bon Secours Cancer Institute at St. Mary's Hospital
Study Chair: Deepak Khuntia, MD University of Wisconsin, Madison
  More Information

Additional Information:
No publications provided

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00566852     History of Changes
Other Study ID Numbers: RTOG-0614, CDR0000577872, NCI-2009-00735
Study First Received: December 1, 2007
Last Updated: December 20, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Radiation Therapy Oncology Group:
cognitive/functional effects
neurotoxicity
tumors metastatic to brain
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Neurotoxicity Syndromes
Neoplastic Processes
Pathologic Processes
Nervous System Diseases
Poisoning
Substance-Related Disorders
Memantine
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 16, 2014