MEKTOVI for Pediatric Craniopharyngioma

Recruiting in Palo Alto (17 mi)

+21 other locations

Overseen by Maryam Fouladi, MD

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Nationwide Children's Hospital

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

Disqualifiers: Pregnancy, Gastrointestinal disease, Uncontrolled infection, others

No Placebo Group

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests MEKTOVI, a pill that targets cancer growth proteins, in children and young adults with a recurring brain tumor called Adamantinomatous Craniopharyngioma. The drug works by blocking signals that make cancer cells grow.

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.

What data supports the effectiveness of the drug MEKTOVI (Binimetinib) for treating pediatric craniopharyngioma?

Research shows that MEK inhibitors like binimetinib have been effective in treating craniopharyngiomas, particularly those with specific genetic mutations. Similar drugs, when used in combination with BRAF inhibitors, have shown positive responses in patients with papillary craniopharyngioma, suggesting potential effectiveness for MEKTOVI in similar cases. ^{1 2 3 4 5}

Is MEKTOVI (Binimetinib) safe for use in humans?

The safety of MEKTOVI (Binimetinib) has been evaluated in combination with other drugs for conditions like BRAF-mutant tumors, showing effectiveness, but specific safety data for MEKTOVI alone in humans is not detailed in the provided research. ^{1 3 4 5 6}

Research Team

Holly Lindsay, MD

Principal Investigator

Children's Hospital Colorado

Todd C Hankinson, MD

Principal Investigator

Children's Hospital Colorado

Maryam Fouladi, MD

Principal Investigator

Nationwide Children's Hospital

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Binimetinib (MEK Inhibitor)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Catherine Krawczeski

Nationwide Children's Hospital

Chief Medical Officer

MD

Timothy C. Robinson

Nationwide Children's Hospital

Chief Executive Officer since 2019

BSc in Psychology and Business Administration from Indiana University

Children's Hospital Colorado

Collaborator

Trials

121

Recruited

5,135,000+

Jena Hausmann

Children's Hospital Colorado

Chief Executive Officer since 2015

Master’s degree in Healthcare Administration from the University of Minnesota, B.A. in Political Science from Colorado College

David Brumbaugh

Children's Hospital Colorado

Chief Medical Officer since 2024

MD

Findings from Research

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 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]

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]

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]

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]

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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Medical Therapy for Craniopharyngiomas. [2022]

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

Craniopharyngioma: a roadmap for scientific translation. [2021]

4. England pubmed.ncbi.nlm.nih.gov

BRAF-V600E mutant papillary craniopharyngioma dramatically responds to combination BRAF and MEK inhibitors. [2018]

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

Prognostic Factors and Treatment Impact on Overall Survival in Adult Craniopharyngioma. [2023]

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

Dabrafenib as a diagnostic and therapeutic strategy for the non-surgical management of papillary craniopharyngioma. [2023]