Cognitive Dysfunction, Cognitive Disorder
Conditions
Keywords
MW151, MW01-2-151SRM, whole brain radiation therapy
Brief summary
HYPOTHESIS: MW151 intervention during whole-brain radiotherapy for intracranial metastases is safe and well tolerated 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 evaluated whether MW151 was safe and well tolerated and whether it mitigated neurocognitive decline following whole-brain radiotherapy in adult patients with intracranial metastases from solid tumors.
Detailed description
In Part A, 10 subjects will receive MW151 in an open label evaluation. At least 5 of these subjects will be male. For each subject, safety and tolerability data for the first 24 hours will be reviewed prior to the continuation of dosing. Subjects will be evaluated for safety during week 1, during week 2, and at week 4. Once the data from Part A have been reviewed by the Safety Monitoring Committee (SMC) for males and females, an additional 30 subjects will be recruited to Part B. These subjects will also receive open-label MW-151. In both Parts A and B subjects will take study drug (males), or the first daily dose of study drug (females) before WBRT which will be administered once a day (3Gy), five days a week (Monday to Friday) for two weeks, for total of ten treatments and 30 Gy.
Interventions
DRUGMW151
Females: 20 mg MW151 daily (10 mg capsule BID), for 28 days; Males: 10 mg MW151 daily (10 mg capsule QD), for 28 days.
Sponsors
ImmunoChem Therapeutics, LLC
National Cancer Institute (NCI)
Northwestern Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
A subject will be eligible for inclusion in the study only if all of the following criteria are met: 1. All patients must be willing to and have the capacity to give written informed consent and have signed and dated the informed consent form (ICF) in accordance with ICH and GCP guidelines, as an assurance that all participants understand the risks and benefits of the study 2. All patients must be able to speak and understand English proficiently 3. Histologically or cytologically confirmed diagnosis of a solid tumor malignancy within the past 5 years a. If the original histologic proof of malignancy is \> 5 years, then pathological (i.e., more recent) confirmation is required (e.g., from a systemic metastasis or brain metastasis) 4. Intracranial metastases (either parenchymal brain metastases or leptomeningeal disease (LMD, also known as neoplastic meningitis, leptomeningeal carcinomatosis, or carcinomatous meningitis)) must be visible on contrast-enhanced MRI
Exclusion criteria
A subject will not be eligible for inclusion in the study if any of the following criteria are met: 1. Subject is lactating or is pregnant 2. Severe, active co-morbidity, defined as follows: 1. Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months 2. Transmural myocardial infarction within the last 6 months 3. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration 4. Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration 5. Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects 3. Intractable seizures while on adequate anticonvulsant therapy (i.e., more than one seizure per month for the past 2 months) 4. Clinically significant abnormalities in screening laboratory tests that would affect patient safety as determined by the principal investigator 5. History of psychiatric disorder requiring ongoing medical management 6. History of substance abuse including alcohol within past 5 years Appropriately prescribed medication for the treatment of pain or other symptoms related to the underlying malignancy is acceptable 7. Chronic kidney disease defined as the presence of significant proteinuria on urinalysis and/or eGFR of \<60mL/min, as calculated by the clinical site laboratory 8. Inability to follow the instructions or an unwillingness to cooperate with study procedures 9. Known allergy to any component of MW151 as described in investigator's brochure 10. 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. Concurrent immunotherapy is permitted 11. Prior whole-brain radiotherapy 12. Use of chronic short-acting benzodiazepine 13. 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. 14. Any reason or opinion of the investigator that would prevent the subject from participation in the study 15. Currently receiving treatment with and/or planned treatment with Memantine HCl or combination drugs containing Memantine HCl.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | 28 days | To assess the safety and tolerability of oral administration of MW151 in adult patients with brain metastases. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reduction in Cognitive Deterioration | 6 months | To determine if the addition of MW151 to WBRT standard of care treatment will show a trend towards reduction in cognitive deterioration in patients with brain metastases from solid tumors, as measured by standardized NCF tests. |
| Progression-free Survival and Overall Survival | 6 months | To evaluate intracranial progression-free survival and overall survival following the addition of MW151 to WBRT standard of care treatment for patients with brain metastases. |
| Anti-inflammatory Effects | 6 months | To determine if the addition of MW151 to WBRT will have an impact on plasma levels of proinflammatory cytokines (PIC). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORVinai Gondi, MD
Northwestern Medicine
Participant flow
Recruitment details
The study was initiated on July 1, 2022, and the last follow-up visit was completed on June 11, 2025.
Pre-assignment details
A total of 27 subjects were screened, and 24 subjects were enrolled. One enrolled subject refused treatment; therefore, 23 subjects received open-label MW151 and were included in the Safety Population. Male (10 mg MW151/day) and female (20 mg MW151/day) subjects were analyzed together because the sex-specific dosing regimen was part of the protocol-defined MW151 treatment strategy and did not constitute separate treatment arms.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 59.65 year STANDARD_DEVIATION 13.07 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 21 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 9 / 23 |
| other Total, other adverse events | 23 / 23 |
| serious Total, serious adverse events | 15 / 23 |
Outcome results
None listed