Memantine for Brain Tumor

Not currently recruiting at 150 trial locations

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Children's Oncology Group

Must not be taking: Anticonvulsants, Carbonic anhydrase inhibitors

Disqualifiers: Intractable seizures, Neurodevelopmental disorders, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 14

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether memantine can improve thinking skills like attention and memory in children and teenagers with brain tumors undergoing radiation therapy. Memantine may help by blocking certain brain receptors that can lead to cognitive decline. Participants will receive either memantine (a medication) or a placebo (a pill with no active drug) and will undergo cognitive tests and MRIs to observe any effects over time. Children and teens aged 4 to under 18 years with primary brain tumors, who have not previously received brain radiation and speak English, French, or Spanish, may be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to important research on a promising treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking medications that make your urine more alkaline, you may not be eligible to participate.

Is there any evidence suggesting that memantine hydrochloride is likely to be safe for humans?

Research has shown that memantine hydrochloride is usually well-tolerated. In one study, memantine was combined with drugs like temozolomide, mefloquine, and metformin for patients with glioblastoma, a type of brain cancer. The results indicated that this combination was safe. Another study examined memantine's effect on thinking skills in patients receiving radiation therapy. Those who took memantine scored better on cognitive tests than those who took a placebo, which contains no active medicine.

These findings suggest that memantine might protect the brain from some harmful effects of radiation without causing major side effects. However, it is important to monitor for any possible negative reactions, as with any treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about memantine hydrochloride for brain tumors because it offers a unique approach to treatment by potentially protecting cognitive function. Unlike standard treatments such as surgery, radiation, or chemotherapy, which primarily focus on removing or shrinking tumors, memantine is an NMDA receptor antagonist that may help preserve brain function during and after these aggressive therapies. This focus on cognitive preservation is particularly important for improving the quality of life for patients undergoing brain tumor treatment.

What evidence suggests that memantine might be an effective treatment for brain tumors?

Research has shown that memantine, when used during radiation treatment for brain conditions, can help protect cognitive skills. In studies with patients receiving brain radiation, those who took memantine maintained better attention and memory than those who did not. Specifically, one study found that memantine improved thinking ability scores by about 4 points, while those not taking the drug experienced a decline. This trial will compare memantine with a placebo to further investigate its potential to maintain brain function during treatment for brain tumors. ^{2 3 6 7 8}

Who Is on the Research Team?

Nadia N Laack

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for children and adolescents aged 4-17 with newly diagnosed or recurrent primary brain tumors who haven't had prior cranial radiotherapy. Participants must weigh at least 15 kg, have adequate organ function, be able to undergo MRI scans, and understand English, French or Spanish. They can't join if they have a life expectancy under 18 months, allergies to memantine, uncontrollable seizures despite medication, severe diseases that could affect the study's outcome or are pregnant.

Inclusion Criteria

All patients and/or their parents or legal guardians must sign a written informed consent

The patient must be able to undergo magnetic resonance imaging

I weigh more than 15 kg.

Exclusion Criteria

Life expectancy of less than 18 months

I have a neurodevelopmental disorder like Down syndrome or Fragile X.

Co-morbid systemic illnesses, psychiatric conditions, social situations, or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens or would limit compliance with the study requirements

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Participants receive cranial or craniospinal radiotherapy as part of treatment for primary central nervous system tumors

6 weeks

Daily visits for radiation therapy

Treatment

Participants receive memantine or placebo orally for 24 weeks, with cognitive testing and MRI assessments

24 weeks

Weekly visits for the first 2 weeks, then bi-weekly visits

Follow-up

Participants are monitored for cognitive function and overall survival, with assessments at 12, 24, and 48 months

48 months

Assessments at 12, 24, and 48 months

What Are the Treatments Tested in This Trial?

Interventions

• Memantine Hydrochloride

Trial Overview The trial is testing whether Memantine Hydrochloride can protect cognitive functions like attention and memory in kids receiving radiation therapy for brain tumors compared to usual treatment without Memantine. Cognitive assessments will measure the outcomes.

How Is the Trial Designed?

Group I: Arm I (memantine hydrochloride) Experimental Treatment 5 Interventions

Patients receive memantine hydrochloride orally PO QD for week 1 and then BID for weeks 2-24 in the absence of disease progression or unacceptable toxicity. Patients also complete cognitive testing over 20-30 minutes at baseline, end of radiation therapy, and at 3, 6, 12, 24, and 48 months. Patients undergo MRI and may optionally undergo blood sample collection throughout the trial.

Group II: Arm II (placebo) Placebo Group 5 Interventions

Patients receive placebo PO QD for week 1 and then BID for weeks 2-24 in the absence of disease progression or unacceptable toxicity. Patients also complete cognitive testing over 20-30 minutes at baseline, end of radiation therapy, and at 3, 6, 12, 24, and 48 months. Patients undergo MRI and may optionally undergo blood sample collection throughout the trial.

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

Published Research Related to This Trial

Temozolomide is an effective oral treatment for high-grade glioma and anaplastic astrocytoma, showing not only antitumor effects but also improvements in patients' quality of life.

It has potential advantages for treating neoplastic meningitis due to its ability to penetrate the blood-brain barrier and its demonstrated efficacy in increasing survival in preclinical models, making it a promising candidate for further research in central nervous system cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide in early stages of newly diagnosed malignant glioma and neoplastic meningitis. Friedman, HS.[2018]

Memantine, while generally well-tolerated for neurocognitive protection during cranial radiotherapy, can cause altered mental status, as demonstrated in a case involving an 18-year-old male with medulloblastoma who required ICU admission after starting the medication.

The patient's symptoms improved significantly after memantine was withheld, highlighting the need for clinicians to be cautious and monitor for potential neurocognitive side effects when prescribing memantine, especially in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Life-threatening altered mental status secondary to memantine in an adolescent undergoing cranial radiotherapy for medulloblastoma. Kim, KN., Shah, YB., Croy, C., et al.[2023]

In a phase 3 trial involving 518 patients with brain metastases, the addition of hippocampal avoidance (HA) to whole-brain radiation therapy plus memantine significantly preserved cognitive function over a median follow-up of 12.1 months, reducing the risk of cognitive failure by 26%.

Patients receiving HA-WBRT + memantine reported lower symptom burden and fewer cognitive symptoms at 6 and 12 months, with no significant differences in overall survival or treatment-related toxicity compared to those receiving standard WBRT + memantine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained Preservation of Cognition and Prevention of Patient-Reported Symptoms With Hippocampal Avoidance During Whole-Brain Radiation Therapy for Brain Metastases: Final Results of NRG Oncology CC001. Gondi, V., Deshmukh, S., Brown, PD., et al.[2023]

In a study using mice with implanted brain tumors, gemcitabine significantly increased lifespan by 60-89% at a dose of 25 mg/kg, despite its limited ability to cross the blood-brain barrier (BBB) at only 10% permeability.

Compared to other drugs like carmustine and cyclophosphamide, which had higher BBB permeability, gemcitabine still demonstrated a pronounced therapeutic effect, suggesting that even a small concentration of the drug can be effective against intracranial tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Gemcitabine on Intracranial Erlich Tumor and its Determinants. Stukov, AN., Bespalov, VG., Alexandrov, VA., et al.[2022]

Chemotherapy is a key treatment for various malignant brain tumors, including primary central nervous system lymphomas and malignant gliomas, highlighting its importance in oncology.

New therapies, such as cytostatic agents and molecular therapies, are being explored to improve treatment outcomes for brain tumors, indicating ongoing advancements in cancer care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain tumor treatment: chemotherapy and other new developments. Graham, CA., Cloughesy, TF.[2018]

The new dry syrup formulation of memantine hydrochloride demonstrated bioequivalence to the traditional film-coated tablet, meaning it delivers the same amount of the active ingredient effectively, as shown in two crossover studies with specified dosing conditions.

Both formulations were found to have similar safety profiles, indicating that the new syrup can be a suitable alternative for Alzheimer's disease patients, potentially improving medication adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Bioequivalence of Memantine Tablet and a New Dry Syrup Formulation in Healthy Japanese Males: Two Single-Dose Crossover Studies. Maekawa, Y., Hasegawa, S., Ishizuka, T., et al.[2020]

Current treatments for brain tumors are often inadequate, leading to ongoing research into the use of concurrent chemotherapy and radiotherapy to improve patient outcomes.

Trials are exploring new agents that can effectively cross the blood-brain barrier and minimize overlapping toxicities, which may enhance the safety and efficacy of combined therapies for brain tumor patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent chemotherapy and radiotherapy in patients with brain tumors. Glantz, MJ., Kim, L., Choy, H., et al.[2005]

In a study of 158 patients with intrinsic brain tumors, several chemotherapeutic agents showed notable efficacy, with carmustine (BCNU) having a response rate of 47% and a median duration of response of nine months.

When patients who initially responded to one drug were given a second drug, only 15% showed a response, indicating limited effectiveness of switching treatments after initial therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent chemotherapy of brain tumors. A five-year review. Wilson, CB., Gutin, P., Boldrey, EB., et al.[2019]

Memantine is an effective treatment for moderate-to-severe Alzheimer's disease, acting as a neuroprotective agent by blocking excessive calcium influx through NMDA receptors, which helps maintain normal brain signaling.

While memantine does not cure or reverse Alzheimer's disease, it can enhance cognitive function and is safe to use in combination with other treatments, as supported by various clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Glutamate-related excitotoxicity neuroprotection with memantine, an uncompetitive antagonist of NMDA-glutamate receptor, in Alzheimer's disease and vascular dementia]. Tanović, A., Alfaro, V.[2013]

Whole brain radiation therapy, the primary treatment for brain metastases in low to middle income countries, is linked to irreversible cognitive decline.

Memantine has been shown to help reduce the rate of cognitive decline and delay cognitive failure in cancer patients undergoing whole brain radiotherapy, suggesting it may be a beneficial therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic role of memantine for the prevention of cognitive decline in cancer patients with brain metastasis receiving whole-brain radiotherapy: a narrative review. Folloso, MC., Torres, M., Ciocon, SL., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37150264/

Final Results of NRG Oncology CC001 - PubMed - NIH HA during WBRT + memantine for brain metastases leads to sustained preservation of cognitive function and continued prevention of patient-reported neurologic ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0093775423000659

Efficacy of memantine in preventing neurocognitive ... About 50%–90% of patients with brain metastases who receive radiation therapy experience cognitive impairment. This systematic review aims to gather credible ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04939597

NCT04939597 | A Study to See if Memantine Protects the ... To estimate the 36-month disease-free and overall survival (of primary brain tumor) after memantine treatment compared to placebo. VII. To correlate changes in ...

4. cancer.gov cancer.gov/news-events/cancer-currents-blog/2018/brain-metastases-radiation-therapy-hippocampal-avoidance

Tailored Radiation for Brain Metastases Reduces ... In the NCI-funded trial, patients with brain metastases were treated with the drug memantine (Namenda), which has been shown to help protect ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.2036

Memantine in radiation-induced cognitive dysfunction ... At 24 weeks, memantine arm improved ACE scores by +4 (0 to 12) compared to placebo -8 (-15.5 to -2.5) (p < 0.001). At 24 weeks in WBRT, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7529526/

Memantine for Prevention of Brain Irradiation–Induced ... In a phase I trial, memantine was found to be safe when combined with temozolomide, mefloquine, and metformin in patients with glioblastoma. In ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03194906

Memantine for Prevention of Cognitive Late Effects in ... Children with brain tumors who have had radiation therapy are at risk for problems with attention, memory, and problem solving.

8. e-roj.org e-roj.org/journal/view.php?number=1616

Role of memantine to mitigate radiation-induced cognitive ... Memantine was reported to have the potential to mitigate radiation-induced cognitive dysfunction in patients with brain metastasis receiving WBRT.