ACTIVE_NOT_RECRUITING

Identification of Treatment Concentrations of Defactinib or VS-6766 for the Treatment of Patients With Glioblastoma

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Conditions

GlioblastomaRecurrent Glioblastoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This early phase I trial tests brain concentration level and safety of defactinib or VS-6766 for the treatment of patients with glioblastoma. Recently, two new drugs that seem to work together have been shown to have promising treatment effects in tissue culture and animal models of glioblastoma. Each inhibits a different glioblastoma growth pathway and when used together may create a larger effect on tumor growth than either alone. Growth pathway describes a series of chemical reactions in which a group of molecules in a cell work together to control cell growth. It is known that glioblastoma tumor cells can grow because of lack of regulation. Both Pyk2 and the closely related kinase (FAK) proteins help regulate tumor cell invasion, unless they are produced in large amounts (over expressed). Specifically, Raf and FAK/Pyk2 regulation of cell division is activated quite a bit more in gliomas compared to normal tissues. Recently developed inhibitors of Raf (VS-6766) and FAK (defactinib) which belong to a class of medications called kinase inhibitors, are aimed to bring their activity to proper levels and may stop tumor growth.

Official Title

A Single-Dose Study of Orally Administrated Defactinib or VS-6766 in Patients With Glioblastoma

Quick Facts

Study Start:2023-07-28
Study Completion:2026-10-31
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05798507

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:21 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * New or recurrent glioblastoma diagnosed by neuroimaging techniques for which surgical resection is indicated
  2. * Age older than 21 years
  3. * An Eastern Cooperative Group (ECOG) performance status =\< 1
  4. * Hemoglobin (Hb) \>= 9.0 g/dL. If a red blood cell transfusion has been administered the Hb must remain stable and \>= 9.0 g/dL for at least 1 week prior to first dose of study therapy.
  5. * Platelets \>= 100,000/mm\^3
  6. * Absolute neutrophil count (ANC) \>= 1500/mm\^3
  7. * Total bilirubin =\< 1.5 × upper limit of normal (ULN) per the institution; patients with Gilbert syndrome may enroll if total bilirubin \< 3.0 mg/dL (51 umole/L)
  8. * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 × ULN (or \< 5x ULN in patients with liver metastases)
  9. * Creatinine clearance rate of \>= 50 mL/min as calculated by the Cockcroft-Gault formula or serum creatinine of =\< 1.5 x ULN
  10. * Albumin \>= 3.0 g/dL (451 umole/L)
  11. * Creatine phosphokinase (CPK) =\< 2.5 x ULN
  12. * Left ventricular ejection fraction \>= 50% by echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan
  13. * Baseline QTc interval \< 460 ms for women and =\< 450 ms for men (average of triplicate readings) (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade 1) using Fredericia's QT correction formula. NOTE: This criterion does not apply to subjects with a right or left bundle branch block
  14. * Adequate recovery from toxicities related to prior treatments to at least Grade 1 by CTCAE v 5.0. Exceptions include alopecia and peripheral neuropathy grade =\< 2
  15. * Male and female patients with reproductive potential agree to use highly effective method of contraceptive (per Clinical Trial Facilitation Group \[CFTG\] recommendations) during the trial and for 3 months following the last dose of VS-6766 for male patients, and 1 month following the last dose of VS-6766 for female patients.
  1. * Clinically significant gastrointestinal abnormalities, requirement for systemic anticoagulation or potent CYP 2C8 inhibitors, and history of clinically significant cardiac or pulmonary disorders
  2. * Minors will be excluded from the investigation. Glioblastoma is the major form of brain cancer in people over 50 years old. Pediatric cases of glioblastoma are relatively rare. Besides this, there are crucial molecular differences between adult and pediatric gliomas. Our preliminary data for proposed investigation were obtained on GBM specimens and cultures developed from GBM tissues donated by adult subjects. Results of investigation of adult glioma tissue cannot simply be extrapolated to children. Therefore, our primary research focus is the investigation of GBM in adults. If appropriate, a separate, age-specific study in children will be performed
  3. * Pregnant women will be excluded from the study as altered hormonal and immunological status can affect the study results
  4. * Prisoners will be excluded from the study
  5. * Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy
  6. * History of prior malignancy, with the exception of curatively treated malignancies or malignancies with very low potential for recurrence or progression
  7. * Major surgery within 4 weeks (excluding placement of vascular access), minor surgery within 2 weeks, or palliative radiotherapy within 1 week of the first dose of VS-6766
  8. * Exposure to medications (with or without prescription), supplements, herbal remedies, or foods with potential for drug-drug interactions with VS-6766 within 14 days prior to the first dose of VS-6766 and during the course of therapy, including:
  9. * VS-6766: strong CYP3A4, inhibitors or inducers, due to potential drug-drug interactions with VS-6766 and/or defactinib
  10. * Defactinib: strong CYP3A4, CYP2C9, and P-glycoprotein (P-gp) inhibitors or inducers, due to potential drug-drug interactions with VS-6766 and/or defactinib
  11. * Known hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection that is active and/or requires therapy
  12. * Active skin disorder that has required systemic therapy within the past 1 year
  13. * History of rhabdomyolysis
  14. * Concurrent ocular disorders:
  15. * Patients with history of glaucoma, history of retinal vein occlusion (RVO), predisposing factors for RVO, including uncontrolled hypertension, uncontrolled diabetes
  16. * Patients with history of retinal pathology or evidence of visible retinal pathology that is considered a risk factor for RVO, intraocular pressure \> 21 mm Hg as measured by tonometry, or other significant ocular pathology, such as anatomical abnormalities that increase the risk for RVO
  17. * Patients with a history of corneal erosion (instability of corneal epithelium), corneal degeneration, active or recurrent keratitis, and other forms of serious ocular surface inflammatory conditions
  18. * Concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association \[NYHA\]), myocardial infarction within the last 6 months, unstable arrhythmias, unstable angina, or severe obstructive pulmonary disease
  19. * Patients with the inability to swallow oral medications or impaired gastrointestinal absorption due to gastrectomy or active inflammatory bowel disease
  20. * Patients with a history of hypersensitivity to any of the inactive ingredients (hydroxypropylmethylcellulose, mannitol, magnesium stearate) of the investigational product

Contacts and Locations

Principal Investigator

Jeffrey J Olson, MD
PRINCIPAL_INVESTIGATOR
Emory University Hospital/Winship Cancer Institute

Study Locations (Sites)

Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
United States

Collaborators and Investigators

Sponsor: Emory University

  • Jeffrey J Olson, MD, PRINCIPAL_INVESTIGATOR, Emory University Hospital/Winship Cancer Institute

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-07-28
Study Completion Date2026-10-31

Study Record Updates

Study Start Date2023-07-28
Study Completion Date2026-10-31

Terms related to this study

Additional Relevant MeSH Terms

  • Glioblastoma
  • Recurrent Glioblastoma