Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized Phase III Trial of Memantine and Whole-Brain Radiotherapy With or Without Hippocampal Avoidance in Patients With Brain Metastases
Brief 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.


Options:
A: Inclusion Criteria:

* age \>= 18 years
* recurrence of a histologically confirmed glioblastoma or gliosarcoma
* at least 6 months after first surgery
* at least 6 months after first radiotherapy
* interdisciplinary recommendation for reirradiation
* karnofsky performance status \>= 60, ECOG \<= 2
* creatinine \<= 2,0 mg/dl, urea \<= 100 mg/dl
* ALAT, ASAT \<= 7x upper normal limit

Exclusion Criteria:

* bowel obstruction, subileus
* insulin-dependent diabetes
* decompensated heart failure (NYHA \> 2)
* myocardial infarction within the last 6 months, symptomatic atrial fibrillation
* severe acute infection
* malnutrition, cachexia
* other medical conditions that might increase the risk of the dietary intervention
* pregnancy
* uncontrolled thyroid function
* pancreatic insufficiency
* dementia or other clinically relevant alterations of the mental status which could impair the ability of the patient to apply to the diet or understand the informed consent of the study
B: INCLUSION CRITERIA:

* Histologically or cytologically confirmed non-hematopoietic malignancy within the past 5 years

  * If histologic proof of malignancy is from \> 5 years ago, then a more recent pathological confirmation is required (e.g., from systemic metastatic or brain metastasis)
  * Patients with metastasis of unknown primary tumor are permitted
* Measurable brain metastasis outside a 5-mm margin around either hippocampus on gadolinium contrast-enhanced MRI obtained within the past 30 days
* Have not been or will not be treated with stereotactic radiosurgery (SRS) or surgical resection

  * These treatment options are allowed only at relapse
* Patients who have brain metastases at initial presentation allowed and do not need to demonstrate 3 months of stable scans
* At least 1 week since open biopsy
* Karnofsky performance status 70-100%
* Fertile patients must use effective contraception
* Negative pregnancy test 2 weeks or less prior to study entry
* Patients must be English proficient, with patients who speak English as a second language eligible

EXCLUSION CRITERIA:

* Small cell lung cancer or germ cell malignancy
* Leptomeningeal metastases
* Non-small cell lung cancer-associated brain metastases with ≥ 2 organ sites of extracranial metastases
* Radiologic evidence of hydrocephalus
* Serum creatinine \> 1.4 mg/dL within 30 days prior to study entry
* Pregnant or nursing
* Contraindication to MRI imaging such as implanted metal devices or foreign bodies or severe claustrophobia
* Severe, active co-morbidity including any of the following:

  * Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
  * Transmural myocardial infarction within the past 6 months
  * Acute bacterial or fungal infection requiring intravenous antibiotics
  * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
  * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy
  * Uncontrolled, clinically significant cardiac arrhythmias
* Prior radiotherapy to the brain
* Plan for chemotherapy or targeted therapies during WBRT or during the subsequent 7 days
C: Inclusion Criteria:

1)age 18 and older at time of registration. 2) recursive partitioning class (RPA) I or II. 3) 1 to 3 newly diagnosed brain metastases 4) must be eligible to have all lesions treated by SRS as determined by the radiation oncologist on the basis of location and size. 5)MRI with contrast must be performed with 1 month of registration. 6)Signed informed consent form approved by the IRB agreeing to randomization .

Exclusion Criteria:

1) prior WBRT 2) prior resection of brain metastasis, SRS or Gamma knife. 3) \> 3 brain metastases present on MRI 4) lymphoma, small cell lung cancer, leukemia, germ cell tumors. 5) leptomeningeal disease. 6) unknown primary.7) RPA Class III (i.e. KPS \< 70) 8) pregnancy.

Post-entry exclusion: No post-entry exclusions will be allowed after registration has occurred. All randomized patients will be included in the analysis and those lost to follow-up will be assigned the least favorable outcome (recurrence, death).
D: 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

Answer: D