Study for the Use of TKIs for Treatment of Cognitive Decline Due to Degenerative Dementias

NCT02921477 | Unknown Phase 1

• 1 other identifier: 062016
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

The present study is designed as an open label study of patients with mild cognitive impairment or dementia to evaluate longer term tolerability and potential efficacy of tyrosine kinase inhibitors. Baseline and outcome measures in this study utilize validated tests that are appropriate for repeated measures which are not affected by practice effects. Advantages of this study include the fact that the neuropsychological testing instruments and advanced MRI imaging protocols that have been in routine clinical deployment provide for a high degree of availability and reliability for diagnosis and for monitoring change of status. Quality assurance is tightly controlled. The study population is sufficiently broad and the conditions of interest are sufficiently prevalent so that recruitment of the projected numbers of subjects is not a limiting factor. For a Phase I trial there is a proposed 150 patient sample to determine the frequency of common side effects in the population that is being studied. Subjects will be administered the initial dose of bosutinib, with dosage progressively increased over the course of the study. The initial dose of bosutinib is 100 mg tablet, once per day. The dose will be increased as tolerated up to 300 mg per day. All subjects will be started at 100 mg/day and the dose will be increased by 100 mg each month if the lower dose is tolerated without significant side effects. That is to say, the subject will take 100 mg/day every day for the first month, 200 mg/day every day for the second month, and 300 mg/day every day for the third month and for the remainder of the study, provided that adverse reactions do not prohibit continuation at this dosage. The investigators will be using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 to monitor, evaluate, and report adverse reactions on an ongoing basis. Stopping and dose reduction rules for reported adverse reactions have been taken from the package insert of bosutinib.

Conditions

Mild Cognitive Impairment; Dementia

Keywords

tyrosine kinase inhibitor; bosutinib; bosulif

Outcome Measures

Primary Outcomes (1)

• Number of patients who are discontinued due to tolerability issues related to treatment

  Outcome goal to determine safety and tolerability of study medication

  1 year

Study Arms (1)

Bosutinib Treatment Arm

EXPERIMENTAL

Subjects will be administered the initial dose of bosutinib, with dosage progressively increased over the course of the study. The initial dose of bosutinib is 100 mg tablet, once per day. The dose will be increased as tolerated up to 300 mg per day. The dose will be increased by 100 mg each month if the lower dose is tolerated without significant side effects. That is to say, the subject will take 100 mg/day every day for the first month, 200 mg/day every day for the second month, and 300 mg/day every day for the third month and for the remainder of the study, provided that adverse reactions do not prohibit continuation at this dosage. Stopping and dose reduction rules for reported adverse reactions have been taken from the package insert of bosutinib. The duration of treatment is 1 year.

Drug: bosutinib

Interventions

bosutinib DRUG

Also known as: bosulif, TKI

Bosutinib Treatment Arm

Eligibility Criteria

• Age: 45 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cognitive decline with mild cognitive impairment (Clinical Dementia Rating Stage 0.5) through moderate dementia (CDR Stages 1 and 2)

You may not qualify if:

• Subjects with a history of hypersensitivity to bosutinib
• Subjects with contraindications for lumbar puncture, such as bleeding abnormalities, use of anticoagulant medications, and local skin or spine abnormalities
• Reversible causes of cognitive impairment that explains the clinical status entirely, such as hypothyroidism, depression
• Advanced stages of any terminal illness or any active cancer that requires chemotherapy
• Pre-existing renal impairment
• Pre-existing hepatic impairment
• QT prolongation
• Significant cytopenia
• Cardiovascular, cerebrovascular, and peripheral vascular arterial thrombosis
• Women who are pregnant, may become pregnant, or are breastfeeding
• Women of child-bearing potential and male participants with female partners who are of child-bearing potential
• Subjects unable to give informed consent or in vulnerable categories, such as prisoners

Sponsors & Collaborators

• Neurological Associates of West Los Angeles: lead
• Pfizer: collaborator

Study Sites (1)

Neurological Associates of West LA

Santa Monica, California, 90403, United States

Location

Related Publications (21)

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MeSH Terms

Conditions

Cognitive Dysfunction; Dementia

Interventions

bosutinib

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Sheldon Jordan, MD

  Neurological Associates of West Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Neurologist

Study Record Dates

• First Submitted: September 28, 2016
• First Posted: October 3, 2016
• Study Start: September 1, 2016
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2025
• Last Updated: September 28, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)