MW151 and HA-WBRT in Patients With Brain Metastases (MW151-102)

• ClinicalTrials.gov Identifier: NCT05417282
• Recruitment Status: Recruiting
• First Posted: June 14, 2022
• Last Update Posted: July 11, 2022
• Sponsor: ImmunoChem Therapeutics, LLC
• Collaborators: National Cancer Institute (NCI); Northwestern Medicine
• Information provided by (Responsible Party): ImmunoChem Therapeutics, LLC

Tracking Information

• First Submitted Date: June 6, 2022
• First Posted Date: June 14, 2022
• Last Update Posted Date: July 11, 2022
• Actual Study Start Date: July 1, 2022
• Estimated Primary Completion Date: December 14, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 8, 2022)

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 28 days ]

To assess the safety and tolerability of oral administration of MW151 in adult patients with brain metastases.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 8, 2022)

• Reduction in cognitive deterioration [ Time Frame: 6 months ]
  To determine if the addition of MW151 to HA-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.
• Anti-inflammatory effects [ Time Frame: 6 months ]
  To determine if the addition of MW151 to HA-WBRT will have an impact on plasma levels of proinflammatory cytokines (PIC).
• Progression-free survival and overall survival [ Time Frame: 6 months ]
  To evaluate intracranial progression-free survival and overall survival following the addition of MW151 to HA-WBRT standard of care treatment for patients with brain metastases.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: MW151 and HA-WBRT in Patients With Brain Metastases
• Official Title: Safety and Tolerability of MW151 Administered With Hippocampal Avoidant Whole Brain Radiation Therapy (HA-WBRT) in Patients With Brain Metastases

Brief Summary

HYPOTHESIS: MW151 intervention will attenuate radiation induced cognitive impairment caused by hippocampal-avoidant whole brain radiation therapy (HA-WBRT) for brain metastases.

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 MW151 as a mitigator of cognitive dysfunction caused by HA-WBRT in adult patients with brain metastases from solid tumors, as compared with a control group of patients receiving HA-WBRT and placebo.

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 also 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), an additional 30 subjects will be recruited to Part B. These subjects will be randomly assigned to MW151 or placebo in a 1:1 ratio.

In both parts A and B subjects will take study drug (males), or the first daily dose of study drug (females) before HA-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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Cognitive Dysfunction, Cognitive Disorder

Intervention

Drug: MW151

Females: 20 mg MW151 daily (10 mg capsule BID), for 28 days; Males: 10 mg MW151 daily (10 mg capsule QD), for 28 days.

Study Arms

• Experimental: Part A: Open Label
  10 subjects will receive MW151 in an open label evaluation.
  Intervention: Drug: MW151
• Experimental: Part B: Randomized, placebo-controlled
  30 subjects will be randomly assigned to MW151 or placebo in a 1:1 ratio.
  Intervention: Drug: MW151

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 8, 2022): 40
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 14, 2024
• Estimated Primary Completion Date: December 14, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

IInclusion 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 in accordance with ICH and GCP guidelines
  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. Brain metastases must be visible on contrast-enhanced MRI

     a. Patients who had undergone radiosurgery or surgical resection and are planning adjuvant HA-WBRT do not have to have visible disease but do need a baseline MRI

  5. Karnofsky performance status 70-100%
  6. Serum creatinine ≤ 3 mg/dL and creatinine clearance ≥ 30 mL/min as determined by Cockcroft-Gault
  7. Negative urine pregnancy test within 14 days of Day 1 for Women of Childbearing Potential

  8. Women of childbearing potential and men with female partners of childbearing potential must have no plans for further conception and must practice adequate contraception

     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 or placebo 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 HA-WBRT.

      Concurrent immunotherapy is permitted

  11. Prior whole-brain radiotherapy
  12. Use of chronic short-acting benzodiazepine
  13. Use of NSAIDS or steroids within 3 days prior to dosing
  14. Any reason or opinion of the investigator that would prevent the subject from participation in the study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Victor Shifrin, PhD; (617) 872-0639; vshifrin@ic-rx.com

Contact: Karen Bowen, RN; (859) 396-4655; bowen73@windstream.net

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05417282
• Other Study ID Numbers: MW151-102; R44CA236382 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: ImmunoChem Therapeutics, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: ImmunoChem Therapeutics, LLC
• Original Study Sponsor: Same as current

Collaborators

• National Cancer Institute (NCI)
• Northwestern Medicine

Investigators

• Principal Investigator: Vinai Gondi, MD; Northwestern Medicine

• PRS Account: ImmunoChem Therapeutics, LLC
• Verification Date: July 2022