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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

December 1, 2007
December 20, 2013
March 2008
November 2011   (final data collection date for primary outcome measure)
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 ]
Cognitive function, specifically memory, from baseline to 24 weeks from the start of drug treatment as measured by the Hopkins Verbal Learning Test for delayed recall (HVLT-delayed recall)
Complete list of historical versions of study NCT00566852 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Decline in cognitive function, specifically memory, from baseline to 8 weeks, 16 weeks, and 12 months from the start of treatment as measured by the HVLT-delayed recall
  • Neurocognitive failure as measured by a battery of tests
  • Quality-of-life as measured by the Functional Assessment of Cancer Therapy Brain subscale (FACT-Br)
  • Progression-free survival
Not Provided
Not Provided
 
Memantine in Preventing Side Effects in Patients Undergoing Whole-Brain Radiation Therapy for Brain Metastases From Solid Tumors
A Randomized, Phase III, Double-Blind, Placebo-Controlled Trial of Memantine for Prevention of Cognitive Dysfunction in Patients Receiving Whole-Brain Radiotherapy

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.

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.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Supportive Care
  • Cognitive/Functional Effects
  • Metastatic Cancer
  • Neurotoxicity
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Drug: memantine hydrochloride
    Given orally
  • Other: placebo
    Given orally
  • Radiation: radiation therapy
    Patients undergo whole-brain radiotherapy (WBRT) 5 days a week for 3 weeks.
  • 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.
    Interventions:
    • Drug: memantine hydrochloride
    • Radiation: radiation therapy
  • 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.
    Interventions:
    • Other: placebo
    • Radiation: radiation therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
554
Not Provided
November 2011   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00566852
RTOG-0614, CDR0000577872, NCI-2009-00735
Yes
Radiation Therapy Oncology Group
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
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
Radiation Therapy Oncology Group
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP