Can a drug duo prime the brain to fight aggressive tumors?

NCT ID NCT07778602

What the study statuses mean

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Recruitment status, easiest to join first

Recruiting now
This trial is taking on new participants right now.
Not yet recruiting This study
Registered, but not yet taking participants.
By invitation only
Not open to general applications. Only people the study team invites can take part.
Paused
Paused for now. It may or may not start again.
Ongoing
Running, but no longer taking on new participants.
Completed
The trial has finished. Results may not be published yet.
Stopped early
Stopped early, before it reached the end. That can be for many reasons, including safety.
Cancelled
Cancelled before anyone took part.

Expanded access (not trials)

Expanded access
Not a trial. This treatment can be requested outside a study, case by case, for people who qualify.
Expanded access (paused)
Not a trial. The treatment can normally be requested outside a study, but is unavailable right now.
Expanded access (ended)
Not a trial. The treatment could once be requested outside a study, but no longer can.
Approved
The treatment has been approved, so it is available normally rather than through this programme.

When the status isn't known

Details not published
The full record has not been published yet, so there is little to show here.
Status unknown
This status has not been confirmed recently, so it may be out of date.

First seen Aug 21, 2026 · Last updated Aug 27, 2026 · Updated 2 times

Summary

This trial is testing whether two oral drugs, avutometinib and defactinib, can be safely given to people with newly diagnosed high-grade gliomas, a type of aggressive brain cancer. Participants first take the drugs for one cycle before starting standard radiation, and those with a specific tumor marker (MGMT-unmethylated) continue the drugs during radiation. The main goals are to see if this treatment plan is feasible and safe, and to measure any early tumor shrinkage.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance
avutometinib and defactinib
What this could lead to
If this works, it could point toward a new way to treat high-grade gliomas, potentially improving outcomes for patients with these aggressive brain tumors.
What could go wrong
This is a very early, small trial focused on safety and feasibility, not effectiveness. The drugs may cause side effects, and it's unknown if they will improve survival or tumor response.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Early phase 1

The earliest testing in people: a first look at safety, in a very small group.

Participants

About 22 people

The number the study aims to enrol. It can still change while the study runs.

Expected to start

Nov 2026

An estimate. Start dates often move.

Expected to finish

Dec 2029

An estimate. End dates often move.

Lead sponsor

Other sponsor

The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Patient must be able to provide written informed consent. * ≥ 18 years of age * Likely high-grade glioma based on frozen pathology in patients with no prior diagnosis of a glioma or astrocytoma. * Patient appropriate for standard therapy for high-grade glioma that includes 6 weeks of radiation. * Patient is not deemed at a high risk of symptomatic progression within 4 weeks by the treating physician and investigator team. * Karnofsky Performance Scale (KPS) ≥ 70%. * Post-operative MRI completed with 72 hours of surgery that includes FLAIR sequences * Measurable disease per RANO 2.0 enhancing criteria. Leptomeningeal disease not allowed. * Patient is on a tapering dose of steroids anticipated to be on a total daily dose of dexamethasone \< 2 mg for at least 5 days by start of study intervention. * Willing to submit archival tumor sample if available * Adequate organ and marrow function defined as: * Ability to swallow and retain orally administered medications (no liquid suspensions available). * Female participants of childbearing potential must have a negative serum pregnancy test prior to study start. * Male participants must also be documented to be surgically sterile or agree to use adequate contraception and not to donate sperm * Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder. Patients with other malignancies must be disease-free for \> 2 years. * Patients with human immunodeficiency virus (HIV) who are on effective antiretroviral therapy are eligible if the viral load was assessed as undetectable within 6 months prior to baseline. Exclusion Criteria: * Any prior glioma or astrocytoma, or any prior cancer diagnosis resulting in irradiation of the skull or scalp * Significant bi-hemispheric disease or midline shift observed on post-operative MRI likely to result in rapid clinical deterioration * Those who have undergone diagnostic biopsy only for suspected primary brain cancer. * Those who are on other investigational agents at the time of screening and including patients on carmustine and/or gamma tiles * History of clinically significant ophthalmologic disorders * Impairment in gastrointestinal function or disease that may significantly alter the absorption of oral study drug * Clinically significant cardiovascular disease * History of recent (≤ 90 days) thromboembolic or cerebrovascular event * Known history of any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection, and/or detectable virus. * Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring antibiotics or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible. * Patients may not take any of the listed contraindicated medications for 7 days prior to the start of study drug, with the exception of dexamethasone; see section 5.6 "concomitant therapy": 1. Warfarin 2. Strong CYP2C9 or CYP3A4 inhibitors or inducers 3. P-glycoprotein inhibitors or inducers * Patients may not be on H2 blocker or PPI (Proton pump inhibitors) for 2 days prior to start of study drug. * Subjects with a history of hypersensitivity to any of the active or inactive ingredients (hydroxypropylmethylcellulose, mannitol, magnesium stearate) of the investigational products. * Pregnant or breastfeeding * Active or past medical history of interstitial lung disease (ILD)/pneumonitis, including drug-induced or radiation ILD/pneumonitis, pulmonary fibrosis, or adult respiratory distress syndrome (ARDS * History of medically significant rhabdomyolysis

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Conditions

The condition(s) this trial relates to.

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

How to take part

Only the study team decides who joins. These are the ways to reach them.

  1. The places running it

    3 sites in 2 countries. The list below names each one and where it is.

  2. The official record

    ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.

    Open the record ↗

  3. A doctor treating you

    A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.

Contacts and locations

Locations

  • Emory University

    Atlanta, Georgia, 30322, United States

  • Johns Hopkins SKCCC

    Baltimore, Maryland, 21287, United States

  • Universidad Central del Caribe

    Bayamón, 00960-6032, Puerto Rico

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