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

40 Participants Needed

Trial Summary

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.

How does the drug MW151 differ from other treatments for cognitive impairment due to brain radiation therapy?

MW151 is unique because it is being studied specifically for its potential to address cognitive impairment caused by brain radiation therapy, a condition for which there are no standard treatments. Unlike other drugs like memantine, which are used to prevent cognitive decline during whole-brain radiotherapy, MW151 may offer a novel approach by targeting different mechanisms involved in radiation-induced cognitive issues. ^{1 2 3 4 5}

How does the drug MW151 differ from other treatments for cognitive impairment due to brain radiation therapy?

MW151 is unique because it targets specific pathways in the brain to reduce inflammation, which is thought to contribute to cognitive decline after radiation therapy. This approach is different from other treatments like memantine, which primarily focus on protecting brain cells from damage. ^{1 2 3 4 5}

What is the purpose of this trial?

HYPOTHESIS: MW151 intervention during whole-brain radiotherapy for intracranial metastases is safe and will mitigate neurocognitive decline. RATIONALE: There is non-clinical evidence that MW151 reduces brain inflammation and improves neurocognitive outcomes in animal models of radiation therapy induced cognitive dysfunction, and in animal models of other CNS disorders. PURPOSE: This feasibility trial will study whether MW151 mitigates neurocognitive decline following whole-brain radiotherapy in adult patients with intracranial metastases from solid tumors.

Research Team

Vinai Gondi, MD

Principal Investigator

Northwestern Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

References

1. England 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. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Prescription of memantine during non-stereotactic, brain-directed radiation among patients with brain metastases: a population-based study. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Patients with pretreatment leukoencephalopathy and older patients have more cognitive decline after whole brain radiotherapy. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Radiation-induced cognitive toxicity: pathophysiology and interventions to reduce toxicity in adults. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Complications from radiotherapy. [2016]