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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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Neurotoxicity Syndromes
Chemically-Induced Disorders
Neoplasms
Neoplastic Processes
Nervous System Diseases
Pathologic Processes
Poisoning
Memantine
Anti-Dyskinesia Agents
Antiparkinson Agents
Central Nervous System Agents
Dopamine Agents
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014