Navtemadlin for Brain Cancer

Recruiting at 10 trial locations

Overseen By Roy E. Strowd

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must be taking: Corticosteroids

Must not be taking: EIAEDs, Herbal medicines, CYP3A4 substrates, QT prolonging drugs

Disqualifiers: Uncontrolled illness, Active infection, Cardiac arrhythmia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

86 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of navtemadlin in treating patients with glioblastoma (brain cancer) that is newly diagnosed or has come back (recurrent). Navtemadlin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before participating. If you are on enzyme-inducing anti-epileptic drugs, you must stop them at least 10 days before starting the trial. Additionally, you cannot use herbal or non-traditional medications, and certain drugs that interact with the trial medication must be switched to alternatives at least 14 days prior to the trial.

What makes the drug Navtemadlin unique for treating brain cancer?

Navtemadlin is unique because it targets a specific protein interaction in cancer cells, potentially offering a new approach for treating brain cancer, unlike traditional therapies that may not address this specific mechanism. ^{1 2 3 4 5}

Who Is on the Research Team?

Eudocia Lee

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed or recurrent glioblastoma who can swallow pills, have a certain level of physical function (Karnofsky status >= 60%), and normal organ function. Women must not be pregnant and agree to contraception. No other cancer treatments are allowed close to the start of the trial, and no history of severe allergies to similar drugs.

Inclusion Criteria

Creatinine =< institutional ULN

Patients must have MRI within 21 days before starting treatment; patients must be able to tolerate MRI with gadolinium

My glioblastoma has returned or worsened after radiation or chemotherapy.

Exclusion Criteria

I am not taking any medication that reacts badly with the trial drug.

I am HIV-positive and not on antiretroviral therapy.

I have recovered from major side effects of my previous treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part I

Patients with recurrent glioblastoma receive navtemadlin (KRT-232) orally once daily for 2 days, followed by surgery and continued treatment post-recovery.

21 days per cycle

Multiple visits for treatment and monitoring

Treatment Part II

Patients with newly diagnosed glioblastoma undergo radiation therapy and receive navtemadlin (KRT-232) for 6 weeks.

6 weeks

Daily visits for radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 5 years

Every 2 months for the first 2 years, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Navtemadlin

Trial Overview The study tests navtemadlin's safety, tolerable doses, and its ability to reach brain tumors in patients undergoing radiation therapy. It includes MRI scans and biospecimen collection to assess how well navtemadlin works against glioblastoma.

How Is the Trial Designed?

Group I: Treatment (MDM2 inhibitor AMG 232 [KRT-232]) Experimental Treatment 4 Interventions

See Detailed Description

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 19 pediatric and 13 adult ependymomas, a high percentage of pediatric cases (95% for EphA2 and Survivin, 84% for IL-13Rα2) showed overexpression of tumor-associated antigens, indicating potential targets for immunotherapy.

The consistent expression of these antigens in both pediatric and adult ependymomas supports the feasibility of using a peptide-based vaccine targeting these antigens in clinical trials to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased expression of tumor-associated antigens in pediatric and adult ependymomas: implication for vaccine therapy. Yeung, JT., Hamilton, RL., Okada, H., et al.[2021]

Citations

1. England pubmed.ncbi.nlm.nih.gov

A designer peptide against the EAG2-Kvβ2 potassium channel targets the interaction of cancer cells and neurons to treat glioblastoma. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Plasma and cerebrospinal fluid pharmacokinetic study of BNP1350 in nonhuman primates. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

A rare case of malignant pediatric ectomesenchymoma arising from the falx cerebri. [2017]

4. United States pubmed.ncbi.nlm.nih.gov

Increased expression of tumor-associated antigens in pediatric and adult ependymomas: implication for vaccine therapy. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Testosterone Promotes Glioblastoma Cell Proliferation, Migration, and Invasion Through Androgen Receptor Activation. [2023]