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

Sponsor:	Radiation Therapy Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00566852

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 III

Study Type:	Interventional
Study Design:	Allocation: Randomized Masking: Double-Blind 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:

MedlinePlus related topics: Cancer Memory

Drug Information available for: Memantine Memantine hydrochloride

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

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) [ 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 [ Designated as safety issue: No ]
Neurocognitive failure as measured by a battery of tests [ Designated as safety issue: No ]
Quality-of-life as measured by the Functional Assessment of Cancer Therapy Brain subscale (FACT-Br) [ Designated as safety issue: No ]
Progression-free survival [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Adverse events based on CTCAE 3.0 [ Designated as safety issue: Yes ]
Collection of serum, plasma, buffy coat cells, urine, and cerebrospinal fluid for future translational research analyses [ Designated as safety issue: No ]

Estimated Enrollment:	536
Study Start Date:	March 2008
Estimated Primary Completion Date:	June 2012 (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

National Cancer Institute (NCI)

Investigators

Study Chair:	Paul D. Brown, MD	Mayo Clinic
Investigator:	Christina A. Meyers, PhD	M.D. Anderson Cancer Center
Investigator:	Sherry Fox, RN, PhD	Bon Secours Cancer Institute at St. Mary's Hospital
Investigator:	Deepak Khuntia, MD	University of Wisconsin, Madison

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Walter John Curran, Jr, Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:	NCT00566852 History of Changes
Other Study ID Numbers:	CDR0000577872, RTOG-0614
Study First Received:	December 1, 2007
Last Updated:	July 23, 2010
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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 February 09, 2012