MEKTOVI for Pediatric Craniopharyngioma

Recruiting at 23 trial locations

Overseen By Kelsey H Troyer, PhD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Nationwide Children's Hospital

Must not be taking: Investigational drugs, Anti-cancer agents

Disqualifiers: Pregnancy, Gastrointestinal disease, Uncontrolled infection, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

38 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called binimetinib (also known as MEKTOVI) to determine its effectiveness for children and young adults with a rare brain tumor called adamantinomatous craniopharyngioma. The researchers aim to assess the drug's efficacy in individuals who have undergone surgery or radiation but still experience tumor growth. Suitable candidates for the trial are those under 25 diagnosed with this specific tumor type, who have seen it recur or grow after treatment. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on other anti-cancer agents or investigational drugs, and if you're on corticosteroids, the dose must be stable or decreasing for at least 7 days before joining.

Is there any evidence suggesting that MEKTOVI is likely to be safe for pediatric patients with craniopharyngioma?

Research has shown that binimetinib, also known as MEKTOVI, has been tested for safety in treating various tumor types. This pill targets specific proteins that promote tumor growth. In past studies, most participants tolerated binimetinib well. Common side effects included mild skin rash and nausea. Serious side effects were rare, but some patients experienced changes in heart rhythm, which doctors monitored closely.

This trial is in an early stage and aims to gather more safety information for children with craniopharyngioma, a type of brain tumor. While some safety data is available, ongoing research will provide a better understanding. Binimetinib is approved for other conditions in adults, indicating a known safety profile, but its effects in children with this specific condition are still under study. Participants will be closely monitored throughout the trial to ensure their safety. ^{1 2 3 4 5}

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

Researchers are excited about binimetinib for pediatric craniopharyngioma because it offers a new approach by targeting the MEK pathway, which is crucial in cell growth and survival. Unlike traditional treatments such as surgery and radiation, which can have significant long-term side effects, binimetinib is a targeted therapy that may offer a more precise mechanism of action with potentially fewer side effects. This specificity not only opens up the possibility for better management of tumor growth but also provides hope for improved quality of life for young patients facing this challenging condition.

What evidence suggests that MEKTOVI might be an effective treatment for pediatric craniopharyngioma?

Research has shown that MEK inhibitors like binimetinib may help treat craniopharyngiomas, a type of brain tumor. These drugs block a pathway in cells that can cause tumors to grow. Binimetinib specifically targets proteins called MEK1 and MEK2, which are part of this pathway. In this trial, patients with craniopharyngiomas, especially those with certain genetic changes, will receive binimetinib. Although more research is needed, early findings suggest that binimetinib could be effective for children with recurring adamantinomatous craniopharyngioma. ^{1 3 4 5 6}

Who Is on the Research Team?

Todd C Hankinson, MD

Principal Investigator

Children's Hospital Colorado

Maryam Fouladi, MD

Principal Investigator

Nationwide Children's Hospital

Holly Lindsay, MD

Principal Investigator

Children's Hospital Colorado

Are You a Good Fit for This Trial?

This trial is for kids and young adults aged 1 to 25 with recurrent Adamantinomatous Craniopharyngioma, a type of brain tumor. They must have measurable disease, stable health conditions, and meet specific organ function criteria. Those who've had recent surgery or certain treatments aren't eligible.

Inclusion Criteria

Patients must have measurable disease

I have ACP, had surgery, but no prior radiation. I may have had other treatments.

I have waited the required time after my last therapy dose.

Exclusion Criteria

I do not have any major health or surgical issues that could affect my safety or participation in the study.

I haven't had live vaccines recently and don't have an uncontrolled infection.

I have not had recent surgery, substance abuse issues, or specific infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral binimetinib at the recommended phase 2 pediatric dose of 32 mg/m2/dose PO every 12 hours for 4 weeks per cycle, with treatment continuing for up to two years (26 cycles).

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of progression-free survival and adverse events.

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Binimetinib

Trial Overview The trial tests MEKTOVI (binimetinib), an oral drug that blocks specific enzymes in cancer cells. It's given to patients who've had previous surgeries or radiation therapy for their brain tumors. The study aims to see how well it works in these young patients.

How Is the Trial Designed?

Group I: Stratum 1 and Stratum 2 Experimental Treatment 1 Intervention

Stratum 1: Patients with progressive or recurrent adamantinomatous craniopharyngiomas following radiation therapy. Stratum 2: Patients with measurable adamantinomatous craniopharyngioma who have undergone surgery but have not previously received radiation therapy. Progressive disease is allowed but not required

Binimetinib is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation

Approved in European Union as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600 mutation

Approved in Canada as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation

Approved in Japan as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600 mutation

Who Is Running the Clinical Trial?

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Recruited

5,228,000+

Children's Hospital Colorado

Collaborator

Trials

121

Recruited

5,135,000+

Published Research Related to This Trial

Recent advances in understanding the molecular mechanisms of craniopharyngiomas have led to promising medical therapies, particularly for adamantinomatous craniopharyngiomas (ACPs) and papillary craniopharyngiomas (PCPs), which are characterized by distinct genetic mutations.

Targeted treatments, such as MEK inhibitors for ACPs and BRAF inhibitors for PCPs, have shown favorable responses in patients, indicating a shift towards personalized medicine for managing these rare tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical Therapy for Craniopharyngiomas. Alexandraki, KI., Xekouki, P.[2022]

A patient with a BRAF-V600E mutant papillary craniopharyngioma showed significant tumor reduction and neurological improvement after treatment with a combination of BRAF and MEK inhibitors (dabrafenib and trametinib) following unsuccessful radiation therapy.

Despite the successful tumor response, the patient experienced permanent panhypopituitarism, highlighting the need to consider potential long-term side effects of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BRAF-V600E mutant papillary craniopharyngioma dramatically responds to combination BRAF and MEK inhibitors. Roque, A., Odia, Y.[2018]

A 59-year-old man with a suspected papillary craniopharyngioma showed a significant response to the BRAF inhibitor dabrafenib, achieving near complete tumor regression after 6.5 months of treatment, highlighting the efficacy of this targeted therapy for tumors with BRAF V600 mutations.

Dabrafenib not only served as a therapeutic option but also aided in confirming the diagnosis of the tumor, suggesting its potential role in both treatment and diagnosis for patients with similar conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dabrafenib as a diagnostic and therapeutic strategy for the non-surgical management of papillary craniopharyngioma. Lin, AL., Tabar, V., Young, RJ., et al.[2023]

In a study of 666 adult patients with craniopharyngioma, factors such as older age, lack of insurance, and larger tumor size were linked to worse overall survival, highlighting the importance of these demographics in treatment outcomes.

Patients who underwent gross total resection (GTR) or subtotal resection (STR) with adjuvant radiotherapy experienced significantly improved overall survival, while endoscopic resection methods had lower GTR rates but did not affect overall survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic Factors and Treatment Impact on Overall Survival in Adult Craniopharyngioma. Awad, M., Butterfield, JT., Dhawan, S., et al.[2023]

Vemurafenib combined with cobimetinib has shown effectiveness in treating patients with BRAF-mutant papillary craniopharyngioma, a type of brain tumor.

This combination therapy targets specific mutations, suggesting a tailored approach to treatment that could improve outcomes for affected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BRAF-MEK Inhibition Is Effective in BRAFV600E-Mutant Papillary Craniopharyngioma. [2023]

Recent research has identified distinct molecular profiles in craniopharyngiomas, leading to the classification of two subtypes: adamantinomatous and papillary, which can inform targeted treatment strategies.

Targeted inhibitors for the overactive B-Raf signaling found in the papillary subtype show promise for treating recurrent craniopharyngiomas, suggesting a shift towards personalized therapies based on the tumor's molecular characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Craniopharyngioma: a roadmap for scientific translation. Gupta, S., Bi, WL., Giantini Larsen, A., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11937174/

Current clinical trials for craniopharyngiomas - PubMed Central Patients are treated with binimetinib, an oral, highly-selective MEK1/MEK2 inhibitor, twice a day for up to two years. The primary endpoint of ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCT05286788

Binimetinib for the Treatment of Pediatric Progressive or ... This phase II trial tests how well binimetinib works in treating patients with adamantinomatous craniopharyngioma (ACP) that has grown, spread, or gotten worse.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05286788

NCT05286788 | MEKTOVI® for the Treatment of Pediatric ... Phase 2 Study of the MEK Inhibitor MEKTOVI® (Binimetinib) for the Treatment of Pediatric Adamantinomatous Craniopharyngioma. Conditions. Adamantinous ...

4. nicklauschildrens.org nicklauschildrens.org/medical-services/research-institute/open-clinical-trials/onc23127-(connect2108)

The Nicklaus Children's Research Institute Study Details. Phase 2 Study of the MEK Inhibitor MEKTOVI® (Binimetinib) for the Treatment of Pediatric Adamantinomatous Craniopharyngioma.

5. withpower.com withpower.com/trial/phase-2-adamantinoma-5-2022-fad29

MEKTOVI for Pediatric Craniopharyngioma Research shows that MEK inhibitors like binimetinib have been effective in treating craniopharyngiomas, particularly those with specific genetic mutations.

6. cincinnatichildrens.org cincinnatichildrens.org/service/c/clinical-trials/studies/connect2108-9723

CONNECT2108: MEKTOVI® for the Treatment of Pediatric ... The drug will be used to treat pediatric patients diagnosed with recurrent Adamantinomatous Craniopharyngioma including patients who have undergone surgery and ...