Navtemadlin for Brain Cancer

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and understand the side effects of a new treatment called navtemadlin for people with glioblastoma, a type of brain cancer. Navtemadlin blocks enzymes that help tumor cells grow. It targets individuals who have been newly diagnosed or whose cancer has returned. Those who have had glioblastoma, can manage daily life with some help, and haven't recently undergone certain treatments might be suitable for this trial. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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.

Is there any evidence suggesting that navtemadlin is likely to be safe for humans?

Research has shown that navtemadlin, also known as AMG 232, is generally safe for people. One study found that doses up to 240 mg did not cause serious safety issues. Navtemadlin blocks certain proteins that help tumors grow, potentially slowing or stopping cancer cell growth. Although this treatment remains in early testing, the data suggests it is safe for most people at the tested doses. Prospective trial participants might find this information reassuring regarding the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for brain cancer?

Navtemadlin is unique because it targets the MDM2 protein, which plays a crucial role in controlling cell growth and death. Unlike standard treatments for brain cancer, which often include surgery, radiation, and chemotherapy, Navtemadlin aims to inhibit this protein, potentially stopping the cancer cells from multiplying. Researchers are excited because this approach could offer a more targeted treatment option, possibly with fewer side effects compared to traditional methods. By focusing on the MDM2 pathway, Navtemadlin may provide a new avenue for treating brain cancer that current therapies do not address.

What evidence suggests that navtemadlin might be an effective treatment for brain cancer?

Research suggests that navtemadlin, also known as AMG 232, might help treat glioblastoma, a type of brain cancer. It stops the enzymes that tumor cells need to grow. Early studies have shown that navtemadlin affects tumor activity, with some patients reaching the necessary drug levels in their tumors. However, the average time without tumor growth was only 3.1 months. While these results are promising, more research is needed to fully understand its effectiveness. Participants in this trial will receive navtemadlin as part of the study treatment. ^{1 4 6 7 8}

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. clinicaltrials.gov clinicaltrials.gov/study/NCT03107780

NCT03107780 | Testing the Ability of AMG 232 (KRT ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12402800/

Preclinical Modeling of Navtemadlin Pharmacokinetics ... Our translational PK/efficacy model suggests that the minimum effective tumor exposures were achieved only in a minority of patients with GBM. Translational ...

3. dana-farber.org dana-farber.org/clinical-trials/17-453

Phase 0/I study of AMG 232 concentrations in brain tissue ... 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 ...

4. medrxiv.org medrxiv.org/content/10.1101/2024.08.12.24311893v1

Surgical window of opportunity trial reveals mechanisms ... Abstract. We investigated the effectiveness of navtemadlin (KRT-232) in treating recurrent glioblastoma. A surgical window-of-opportunity trial ...

5. science.org science.org/doi/10.1126/scitranslmed.adn6274

A window-of-opportunity trial reveals mechanisms ... Both 120 and 240 mg daily dosing achieved a pharmacodynamic impact, but median progression-free survival was 3.1 months. DNA sequencing of three ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7211202/

Phase 1 study of the MDM2 inhibitor AMG 232 in patients with ... Safety, pharmacokinetics, pharmacodynamics, and efficacy were assessed. Results AMG 232 had acceptable safety up to up to 240 mg. Three ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2012

Pre-clinical modeling of navtemadlin pharmacokinetics (PK ... An open-label, multicenter, phase 2 study of the safety and efficacy of navtemadlin (KRT-232) in patients with TP53 wild-type relapsed/ ...

8. veri.larvol.com veri.larvol.com/news/krt-232/drug

News - navtemadlin (KRT-232) The MDM2 inhibitor Navtemadlin arrests mouse tumor growth and potentiates radiotherapy. Our results support a threshold model for apoptosis induction that ...