MW151 for Cognitive Impairment Due to Brain Radiation Therapy

(MW151-102 Trial)

Overseen By Karen Bowen, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: ImmunoChem Therapeutics, LLC

Must not be taking: Benzodiazepines, NSAIDs, Steroids, Memantine

Disqualifiers: Pregnancy, Heart failure, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 10

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called MW151 to determine if it can protect the brain from cognitive decline (thinking and memory problems) following radiation therapy for brain tumors. Researchers believe MW151 might reduce brain inflammation, potentially improving mental function after treatment. The trial is open to individuals with confirmed solid tumor cancer and visible brain metastases (tumors that have spread to the brain) on an MRI scan. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as chronic short-acting benzodiazepines, chronic NSAID or steroid therapies for chronic inflammatory diseases, and Memantine HCl. You should discuss your current medications with the study team to see if any adjustments are needed.

Do I have to stop taking my current medications for the trial?

You may need to stop taking certain medications, such as short-acting benzodiazepines, chronic NSAIDs, steroids for chronic inflammatory diseases, and Memantine HCl, before and during the trial. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that MW151 is likely to be safe for humans?

Research has shown that MW151 has protected the brain from damage in animal studies. These studies examined conditions similar to those in humans with brain issues caused by radiation. Although MW151 is still undergoing testing in humans, the animal studies suggest it could be safe.

This is a Phase 1 trial, focusing on determining the safety of MW151 for humans. In this early stage, a small group receives the treatment to monitor for any side effects. Serious safety concerns would likely have prevented MW151 from reaching this stage.

In summary, MW151 appears promising based on animal research, and this trial aims to ensure its safety for humans. For those considering participation, it's important to know that the main goal is to assess how well people tolerate the treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for cognitive impairment due to brain radiation therapy, which often focus on managing symptoms, MW151 is designed to target the underlying inflammation at the source. Most current treatments don't address this root cause directly. Researchers are excited about MW151 because it specifically inhibits a type of enzyme involved in the inflammatory response in the brain, potentially offering a more effective approach. This unique mechanism of action could lead to better cognitive outcomes for patients, setting MW151 apart from existing therapies.

What evidence suggests that MW151 might be an effective treatment for cognitive impairment due to brain radiation therapy?

Research has shown that MW151 shows promise in animal studies for reducing brain inflammation and improving cognitive abilities after radiation treatment. Early tests indicate that MW151 can protect against memory and learning issues, particularly in the hippocampus, a brain region crucial for memory. These findings suggest that MW151 might prevent the decline in cognitive skills often seen with whole-brain radiotherapy. While these results are encouraging, they are based on animal studies, and its effectiveness in humans is currently under investigation in this trial. ^{1 2 4 6 7}

Who Is on the Research Team?

Vinai Gondi, MD

Principal Investigator

Northwestern Medicine

Are You a Good Fit for This Trial?

This trial is for adults with brain metastases from solid tumors who can consent, speak English, and have had a recent confirmation of malignancy. They must not be pregnant or have severe health issues like heart failure, infections needing IV antibiotics, jaundice due to liver problems, frequent seizures despite medication, significant psychiatric disorders or substance abuse within the last 5 years.

Inclusion Criteria

My cancer was confirmed by a lab test within the last 5 years.

My brain scans show cancer has spread to my brain.

I am willing and able to sign the consent form after understanding the study's risks and benefits.

Exclusion Criteria

Subject is lactating or is pregnant

Severe, active co-morbidity including 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, intractable seizures while on adequate anticonvulsant therapy (i.e., more than one seizure per month for the past 2 months), clinically significant abnormalities in screening laboratory tests that would affect patient safety as determined by the principal investigator, history of psychiatric disorder requiring ongoing medical management, history of substance abuse including alcohol within past 5 years, chronic kidney disease defined as the presence of significant proteinuria on urinalysis and/or eGFR of <60mL/min, inability to follow the instructions or an unwillingness to cooperate with study procedures, known allergy to any component of MW151 as described in investigator's brochure, received treatment with and/or planned treatment with systemic chemotherapy within 3 days prior, during, or for at least 3 days after completion of whole-brain radiotherapy, prior whole-brain radiotherapy, use of chronic short-acting benzodiazepine, use of chronic NSAID or steroid therapies for chronic inflammatory diseases within 3 days prior to dosing and during the course of the study drug dosing. Use of aspirin for cardiac prophylaxis is acceptable. Use of any other NSAID's or steroids should be reviewed by sponsor, approved and approval documented, any reason or opinion of the investigator that would prevent the subject from participation in the study, currently receiving treatment with and/or planned treatment with Memantine HCl or combination drugs containing Memantine HCl.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MW151 and undergo whole-brain radiotherapy (WBRT) once a day, five days a week for two weeks

2 weeks

10 visits (in-person)

Safety Evaluation

Safety and tolerability data are reviewed for the first 24 hours, and subjects are evaluated for safety during week 1, week 2, and at week 4

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including neurocognitive function and anti-inflammatory effects

6 months

What Are the Treatments Tested in This Trial?

Interventions

• MW151

Trial Overview The study tests if MW151 can prevent cognitive decline when given during whole-brain radiotherapy for patients with intracranial metastases. It's based on evidence that MW151 reduces brain inflammation and improves cognition in animal models.

How Is the Trial Designed?

Group I: Safety and tolerability evaluation Experimental Treatment 1 Intervention

Part A: Open Label sentinel cohort 10 subjects will receive MW151 in an open label safety evaluation. Part B: Open Label 30 subjects will receive MW151.

Who Is Running the Clinical Trial?

ImmunoChem Therapeutics, LLC

Lead Sponsor

Trials

1

Recruited

40+

Northwestern Medicine

Collaborator

Trials

14

Recruited

9,500+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Cranial radiation therapy, especially whole brain radiotherapy (WBRT), is linked to cognitive decline in patients, but the exact mechanisms behind this side effect are still being researched.

The article discusses potential strategies to prevent or reverse cognitive deterioration caused by radiation, as well as advancements in imaging techniques that could help identify brain changes related to treatment and their impact on patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation-induced cognitive toxicity: pathophysiology and interventions to reduce toxicity in adults. Wilke, C., Grosshans, D., Duman, J., et al.[2019]

In a study of 46 patients who underwent whole brain radiotherapy (WBRT) for brain metastases, older age and higher baseline white matter hyperintensity (WMH) volume were found to predict cognitive decline after treatment, as measured by the Montreal Cognitive Assessment (MoCA).

The study suggests that radiation oncologists should be cautious when prescribing WBRT to patients with pre-treatment leukoencephalopathy, as all three patients with severe WMH experienced significant cognitive impairment post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients with pretreatment leukoencephalopathy and older patients have more cognitive decline after whole brain radiotherapy. Chan, M., Ferguson, D., Ni Mhurchu, E., et al.[2021]

In a study of 6220 patients over 65 years old with brain metastases receiving non-stereotactic radiation, only 2.20% were prescribed memantine, despite evidence suggesting it can reduce cognitive decline associated with whole brain radiation therapy (WBRT).

After the publication of the RTOG 0614 trial, memantine prescriptions increased from 1.10% to 5.14%, indicating a slight improvement in its adoption, but overall usage remains low, highlighting the need to address barriers to its prescription.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescription of memantine during non-stereotactic, brain-directed radiation among patients with brain metastases: a population-based study. Lamba, N., Mehanna, E., Kearney, RB., et al.[2021]

In a study of 508 patients receiving whole-brain radiotherapy, memantine was well tolerated and showed a significant delay in cognitive decline compared to placebo, with a hazard ratio of 0.78, indicating a 22% reduction in the risk of cognitive function failure.

While the primary endpoint of delayed recall did not reach statistical significance, memantine demonstrated superior cognitive function outcomes in executive function and processing speed at various time points, suggesting it may help preserve cognitive abilities in patients undergoing radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Brown, PD., Pugh, S., Laack, NN., et al.[2022]

Radiotherapy for brain tumors can lead to significant long-term complications, including neurocognitive impairments and decreased quality of life, particularly in young patients treated for low-grade gliomas.

To minimize these complications while maintaining treatment effectiveness, personalized treatment regimens should be developed, utilizing modern imaging and techniques to target radiation more precisely and protect sensitive brain areas like the hippocampus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications from radiotherapy. Dhermain, F., Barani, IJ.[2016]

Citations

1. redjournal.org redjournal.org/article/S0360-3016(25)02825-1/fulltext

Radiomic Substudy of a Phase 1b Trial of MW151 for ... Pre-clinical testing in animal models of CNS disorders including radiation-induced cognitive impairment has shown MW151 to have neuroprotective effects. In ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-07064

MW151 and Whole-brain Radiotherapy in Patients with ... RATIONALE: There is non-clinical evidence that MW151 reduces brain inflammation and improves neurocognitive outcomes in animal models of radiation therapy ...

3. clinconnect.io clinconnect.io/trials/NCT05417282

MW151 and Whole-brain Radiotherapy in Patients with HYPOTHESIS: MW151 intervention during whole-brain radiotherapy for intracranial metastases is safe and will mitigate neurocognitive decline.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8791470/

Therapeutic treatment with the anti-inflammatory drug ... We found that MW151 was able to partially rescue hippocampal-dependent spatial memory and learning deficits in this comorbidity context.

5. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/33/NCT04120233/Prot_SAP_ICF_000.pdf

Document Coversheet Overall, the nonclinical pharmacology data suggest that MW151 can exert a positive influence on post-injury neurologic outcomes by blunting the ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0360301625028251

Radiomic Substudy of a Phase 1b Trial of MW151 for ... Pre-clinical testing in animal models of CNS disorders including radiation-induced cognitive impairment has shown MW151 to have neuroprotective effects. In this ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6594685/

Treatment of Radiation-Induced Cognitive Decline in Adult ... Radiation-induced cognitive decline (RICD) is considered a late effect of radiation therapy (RT) occurring in 30% or more of patients alive at 4 months after ...