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GlioblastomaEarly Phase 1NCT05798507

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

A Early Phase 1 study testing Avutometinib, Biospecimen Collection and Defactinib in people with Glioblastoma and Recurrent Glioblastoma, run by Emory University at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 21 years and older
Conditions the study is for
Glioblastoma, Recurrent Glioblastoma
What is being tested?
Avutometinib, Biospecimen Collection and Defactinib
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
1 siteUnited States
Study dates
28 Jul 2023to 3 Dec 2027
Phase
Early Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • New or recurrent glioblastoma diagnosed by neuroimaging techniques for which surgical resection is indicated
  • Age older than 21 years
  • An Eastern Cooperative Group (ECOG) performance status =< 1
  • 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.
  • Platelets >= 100,000/mm^3
  • Absolute neutrophil count (ANC) >= 1500/mm^3
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  • 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)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 × ULN (or < 5x ULN in patients with liver metastases)
  • Creatinine clearance rate of >= 50 mL/min as calculated by the Cockcroft-Gault formula or serum creatinine of =< 1.5 x ULN
  • Albumin >= 3.0 g/dL (451 umole/L)
  • Creatine phosphokinase (CPK) =< 2.5 x ULN
  • Left ventricular ejection fraction >= 50% by echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan
  • 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
  • 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
  • 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.

Who cannot join

  • Clinically significant gastrointestinal abnormalities, requirement for systemic anticoagulation or potent CYP 2C8 inhibitors, and history of clinically significant cardiac or pulmonary disorders
  • 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
  • Pregnant women will be excluded from the study as altered hormonal and immunological status can affect the study results
  • Prisoners will be excluded from the study
  • Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy
  • History of prior malignancy, with the exception of curatively treated malignancies or malignancies with very low potential for recurrence or progression
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  • 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
  • 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:
  • VS-6766: strong CYP3A4, inhibitors or inducers, due to potential drug-drug interactions with VS-6766 and/or defactinib
  • Defactinib: strong CYP3A4, CYP2C9, and P-glycoprotein (P-gp) inhibitors or inducers, due to potential drug-drug interactions with VS-6766 and/or defactinib
  • Known hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection that is active and/or requires therapy
  • Active skin disorder that has required systemic therapy within the past 1 year
  • History of rhabdomyolysis
  • Concurrent ocular disorders:
  • Patients with history of glaucoma, history of retinal vein occlusion (RVO), predisposing factors for RVO, including uncontrolled hypertension, uncontrolled diabetes
  • 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
  • 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
  • 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
  • Patients with the inability to swallow oral medications or impaired gastrointestinal absorption due to gastrectomy or active inflammatory bowel disease
  • Patients with a history of hypersensitivity to any of the inactive ingredients (hydroxypropylmethylcellulose, mannitol, magnesium stearate) of the investigational product

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Estimate (or characterize) the concentration of defactinib or avutometinib (VS-6766) that accumulates in the glioblastoma (GBM) and brain around tumor.

II. Assess the safety of the administration of a single oral dose of defactinib or VS-6766 in patients with glioblastoma.

III. Assess the inhibition of Pyk2/FAK or MEK, Erk signaling in tumor and brain around tumor.

IV. Assess the pharmacodynamics of defactinib or VS-6766 in patients with glioblastoma.

OUTLINE: This is a dose-escalation study of defactinib and avutometinib. Patients are assigned to 1 of 2 arms.

ARM I: Patients receive 1 dose of defactinib orally (PO) while on study, prior to planned tumor resection.

ARM II: Patients receive 1 dose of avutometinib PO while on study, prior to planned tumor resection.

Patients undergo blood collection and donate resected tumor tissue while on study.

Being tested
Avutometinib, Biospecimen Collection, Defactinib
Medical subject headings
Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AvutometinibDrug

    Also called CH-5126766, CH5126766, CKI-27, R-7304

    Given PO

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood and tissue sample collection

  • DefactinibDrug

    Given PO

Study groups in NCT05798507
Study groupRoleWhat they receive
Arm I (Defactinib)ExperimentalPatients receive 1 dose of defactinib PO while on study, prior to planned tumor resection. Patients undergo blood collection and donate resected tumor tissue while on study.
Receives: Procedure: Biospecimen Collection; Drug: Defactinib
Arm II (Avutometinib)ExperimentalPatients receive 1 dose of avutometinib PO while on study, prior to planned tumor resection. Patients undergo blood collection and donate resected tumor tissue while on study.
Receives: Drug: Avutometinib; Procedure: Biospecimen Collection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Concentration of defactinib that accumulates in the glioblastoma (GBM) and brain around tumor

    Defactinib concentration will be measured in a sample of the glioblastoma, brain around the glioblastoma, and in a serum sample from each subject receiving Defactinib. Descriptive statistics, such as mean and standard deviation, will be generated with these results. Concentration will be compared between dose levels within study drug using two-sample t-tests or non-parametric equivalents such as Mann Whitney U tests.

    Measured: At time of surgery

  2. Concentration of avutometinib (VS-6766) that accumulates in the GBM and brain around tumor

    VS-6766 concentration will be measured in a sample of the glioblastoma, brain around the glioblastoma, and in a serum sample from each subject receiving VS-6766. Descriptive statistics, such as mean and standard deviation, will be generated with these results. Concentration will be compared between dose levels within study drug using two-sample t-tests or non-parametric equivalents such as Mann Whitney U tests.

    Measured: At time of surgery

  3. Incidence of adverse events associated with defactinib

    Will be assessed by quantification of the recognized side effects of this agent including fatigue, nausea, diarrhea, vomiting, hyperbilirubinemia, decreased appetite, peripheral edema, dizziness, and headache and by monitoring for new or undescribed adverse events. Summary statistics will include frequencies and percentages of adverse events.

    Measured: Up to 2 weeks post surgery

  4. Incidence of adverse events associated with VS-6766

    Will be assessed by quantification of the recognized side effects of this agent including rash, creatine phosphokinase elevation, visual disturbances, hypoalbuminemia, and fatigue and by monitoring for new or undescribed adverse events. Summary statistics will include frequencies and percentages of adverse events.

    Measured: Up to 2 weeks post surgery

Secondary outcomes (2)

  1. Pyk2 and FAK phosphorylation in tumor, brain around tumor, and serum

    These results will be summarized with descriptive statistics. These results will be compared to current and historical control samples of glioblastoma (collected in our previous human GBM specimens' studies) and analyzed in parallel with study subject samples and run on one western blot membrane to reduce technique variation. The mean phosphorylation will be compared between groups using two-sample t-test or non-parametric equivalents such as Mann Whitney U tests. Dose levels will be compared to a historical control, both alone and combined.

    Measured: At time of surgery

  2. MEK and Erk in tumor, brain around tumor, and serum

    These results will be summarized with descriptive statistics. These results will be compared to current and historical control samples of glioblastoma (collected in our previous human GBM specimens' studies) and analyzed in parallel with study subject samples and run on one western blot membrane to reduce technique variation. Phosphorylation will be compared between dose levels within study drug using two-sample t-tests or non-parametric equivalents such as Mann Whitney U tests.

    Measured: At time of surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Apr 2023
  2. Study start28 Jul 2023
  3. Primary completion3 Dec 2026 (estimated)
  4. Study completion3 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05798507
Sponsor's protocol ID
STUDY00004876
Other IDs
NCI-2023-00602, STUDY00004876, WINSHIP5751-22, P30CA138292
Status last verified
Dec 2025
First submitted
3 Mar 2023
Last updated
15 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Del Valle MM, Colon EM, Kettimuthu K, Maner-Smith K, Olson JJ, Kucheryavykh LY. Window of opportunity study measuring defactinib and avutometinib delivery in glioblastomas. Cancer Chemother Pharmacol. 2026 Mar 6;96(1):22. doi: 10.1007/s00280-026-04870-4.

    PubMed 41790275

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Avutometinib, Biospecimen Collection and Defactinib in people with Glioblastoma and Recurrent Glioblastoma, run by Emory University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 15 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Concentration of defactinib that accumulates in the glioblastoma (GBM) and brain around tumor (time frame: At time of surgery). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05798507, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2025.

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