Overview

Memantine Hydrochloride and Whole-Brain Radiotherapy With or Without Hippocampal Avoidance in Reducing Neurocognitive Decline in Patients With Brain Metastases

Status:
Completed
Trial end date:
2019-08-26
Target enrollment:
0
Participant gender:
All
Summary
This randomized phase III trial compares memantine hydrochloride and whole-brain radiotherapy with or without hippocampal avoidance in reducing neurocognitive decline in patients with cancer that has spread from the primary site (place where it started) to the brain. Whole brain radiotherapy (WBRT) is the most common treatment for brain metastasis. Unfortunately, the majority of patients with brain metastases experience cognitive (such as learning and memory) deterioration after WBRT. Memantine hydrochloride may enhance cognitive function by binding to and inhibiting channels of receptors located in the central nervous system. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Using radiation techniques, such as intensity modulated radiotherapy to avoid the hippocampal region during WBRT, may reduce the radiation dose to the hippocampus and help limit the radiation-induced cognitive decline. It is not yet known whether giving memantine hydrochloride and WBRT with or without hippocampal avoidance works better in reducing neurocognitive decline in patients with brain metastases.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
NRG Oncology
Collaborator:
National Cancer Institute (NCI)
Treatments:
Memantine
Criteria
Inclusion Criteria:

- PRIOR TO STEP 1 REGISTRATION:

- Brain metastases outside a 5-mm margin around either hippocampus must be visible
on contrast-enhanced magnetic resonance imaging (MRI) performed =< 21 days prior
to Step 1 registration; an allowed exception, regarding ability to image brain
metastases, would be that patients who had undergone radiosurgery or surgical
resection and are planning adjuvant WBRT do not have to have visible disease but
do need a pre-surgery MRI or computed tomography (CT) scan demonstrating brain
metastases; however, the brain metastases could not have been within 5 mm of
either hippocampus

- Patients must have a gadolinium contrast-enhanced three-dimensional spoiled
gradient (SPGR), magnetization-prepared rapid gradient echo (MP-RAGE), or turbo
field echo (TFE) axial MRI scan with standard axial and coronal gadolinium
contrast-enhanced T1-weighted sequence and axial T2/FLAIR sequence acquisitions;
to yield acceptable image quality, the gadolinium contrast-enhanced
three-dimensional SPGR, MP-RAGE, or TFE axial MRI scan should use the smallest
possible axial slice thickness not exceeding 1.5 mm; the associated coronal and
sagittal contrast-enhanced T1 sequences can be up to 2.5 mm in slice thickness;
this MRI must be obtained =< 21 days prior to step 1 registration; the vendor
specific MRI protocols are available for download from the Alzheimer's Disease
Neuroimaging Initiative (ADNI)

- Patients must provide study-specific informed consent prior to registration

- PRIOR TO STEP 2 REGISTRATION:

- The following baseline neurocognitive assessments must be completed prior to Step
2 registration: HVLT-R, TMT, and COWA;

- Pathologically (histologically or cytologically) proven diagnosis of solid tumor
malignancy within 5 years prior to Step 2 registration

- History and physical examination within 28 days prior to Step 2 registration

- Karnofsky performance status of >= 70 within 28 days prior to Step 2 registration

- Serum creatinine =< 3 mg/dL (265 umol/L) and creatinine clearance >= 30 ml/min

- Blood urea nitrogen (BUN) within institutional upper limit of normal (e.g. < 20
mg/dL)

- Total bilirubin =< 2.5 mg/dL (43 umol/L)

- Patients may have had prior therapy for brain metastasis, including radiosurgery
and surgical resection; patients must have completed prior therapy by at least 14
days prior to Step 2 for surgical resection and 7 days for radiosurgery

- Negative serum pregnancy test (in women of childbearing potential) =< 14 days
prior to Step 2; women of childbearing potential and men who are sexually active
must practice adequate contraception while on study

- Patients who are primary English or French speakers are eligible

Exclusion Criteria:

- Prior external beam radiation therapy to the brain or whole brain radiation therapy

- Planned cytotoxic chemotherapy during the WBRT only; patients may have had prior
chemotherapy

- Radiographic evidence of hydrocephalus or other architectural distortion of the
ventricular system, including placement of external ventricular drain or
ventriculoperitoneal shunt

- 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 acute respiratory
illness precluding study therapy at the time of registration

- Severe hepatic disease defined as a diagnosis of Child-Pugh class B or C hepatic
disease

- Renal tubular acidosis or metabolic acidosis

- Human immunodeficiency virus (HIV) positive with cluster of differentiation (CD)4
count < 200 cells/microliter; note that patients who are HIV positive are
eligible, provided they are under treatment with highly active antiretroviral
therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior
to registration; Note also that HIV testing is not required for eligibility for
this protocol

- Pregnant or lactating women, or women of childbearing potential and men who are
sexually active and not willing/able to use medically acceptable forms of
contraception

- Prior allergic reaction to memantine (memantine hydrochloride)

- Current alcohol or drug abuse (may exacerbate lethargy/dizziness with memantine)

- Intractable seizures while on adequate anticonvulsant therapy-more than 1 seizure per
month for the past 2 months

- Patients with definitive leptomeningeal metastases

- Patients with brain metastases from primary germ cell tumors, small cell carcinoma,
unknown primary, or lymphoma

- Contraindication to magnetic resonance (MR) imaging such as implanted metal devices or
foreign bodies

- Contraindication to gadolinium contrast administration during MR imaging, such as
allergy or insufficient renal function

- Current use of (other N-methyl D-aspartate [NMDA] antagonists) amantadine, ketamine,
or dextromethorphan