MEKTOVI® for the Treatment of Pediatric Adamantinomatous Craniopharyngioma

April 3, 2026 updated by: Nationwide Children's Hospital

Phase 2 Study of the MEK Inhibitor MEKTOVI® (Binimetinib) for the Treatment of Pediatric Adamantinomatous Craniopharyngioma

MEKTOVI (binimetinib) is an oral, highly selective reversible inhibitor of mitogen-activated extracellular signal regulated kinase 1 (MEK1) and MEK2. The biological activity of binimetinib that has been evaluated bith in vitro and in vivo in a wide variety of tumor types In this Phase II, the drug will be used to treat pediatric patients diagnosed with recurrent Adamantinomatous Craniopharyngioma including patients who have undergone surgery and/or radiation therapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Adamantinomatous Craniopharyngioma (ACP) is a highly debilitating pediatric brain tumor that lacks medical anti-tumor therapies. Current therapy, which depends largely on surgery and radiation, is associated with poor quality of life and becomes more challenging and risky in the setting of recurrent disease. Recent discoveries regarding the biological characteristics of ACP indicate that available agents, including Mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway inhibitors may have efficacy in the control of ACP. Binimetinib is one such agent.

In this study, up to 38 patients will receive oral binimetinib at the recommended phase 2 pediatric dose (RP2D) of 32 mg/m2/dose PO every 12 hours for 4 weeks which represents one cycle. Cycles will last 28 days and treatment may continue for up to two years (26 cycles).

It will be a multi-center Phase 2 trial with two strata for patients aged >1 year and <39 years with measurable ACP who may have been previously treated with radiation (Stratum 1, 19 patients) or without radiation (Stratum 2, 19 patients, NOT CURRENTLY ENROLLING).

Study Type

Interventional

Enrollment (Estimated)

38

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • New South Wales
      • Randwick, New South Wales, Australia, 2031
    • Queensland
      • South Brisbane, Queensland, Australia, 4101
    • Western Australia
      • Perth, Western Australia, Australia, 6000
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V6H 3N
        • Recruiting
        • British Columbia Children's Hospital
        • Contact:
    • Quebec
      • Montreal, Quebec, Canada
  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20010
    • Florida
      • Miami, Florida, United States, 33155
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Recruiting
        • Cincinnati Children's Hospital Medical Center
        • Contact:
      • Columbus, Ohio, United States, 43205

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 25 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age: Patients must be ≥ 12 months and ≤ 39 years of age at the time of study enrollment.
  2. Diagnosis: Patients with histologically-confirmed adamantinomatous craniopharyngioma (ACP) Histologic confirmation of ACP may be made on solid tumor or, if no solid tumor can be safely obtained, cyst fluid with classic ACP characteristics of thick, cholesterol-rich, greenish-brown liquid in the context of imaging features consistent with craniopharyngioma, including lobulated, cystic/solid mass with calcifications that originates in the sellar/suprasellar region.

  3. Disease Status: Patients must have measurable disease.

    • Stratum 1: Patients with progressive or recurrent ACP who demonstrate cystic and/or solid recurrence or progression at least 6 months post completion of radiation therapy
    • Stratum 2 (NOT CURRENTLY ENROLLING): Patients with measurable ACP who have undergone surgery but have NOT previously undergone irradiation (but may have received prior systemic or intracystic therapy). Progressive disease is allowed but not required.
  4. Performance Level: Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix I). Note: Neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.

  5. Prior Therapy: Patients must have recovered or stabilized from the acute toxic effects of prior treatments

    • Biologic (anti-neoplastic agent): At least 7 days must have elapsed after the last (systemic or intracystic) dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair
    • Immunotherapy: At least 42 days after the completion of any type of systemic immunotherapy, e.g. tumor vaccines.
    • Monoclonal antibodies: At least 21 days after the last dose of a monoclonal antibody.
    • Radiation therapy: Patients must have had their last (conventional or hypofractionated) fraction of: a) Focal irradiation > 6 months prior to enrollment and b) No prior craniospinal irradiation is permitted.
    • Corticosteroids: Patients receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to enrollment
    • Myelosuppressive systemic therapy: At least 21 days must have elapsed after the last systemic myelosuppressive therapy.
    • Surgery: At least 6 weeks must have elapsed since major or intermediate surgery. Major surgery includes major craniotomy for tumor resection of cyst fenestration, organ resection, and exploratory laparotomy. Intermediate procedures include ventriculoperitoneal shunt placement, stereotactic brain biopsy, and intraventricular catheter placement. Minor procedures that are not excluded include skin biopsy/incision and drainage, bone marrow aspirate, and central venous catheter placement, ommaya aspirations, lumbar punctures, and nasal endoscopy to remove packing.

  6. Organ Function Requirements

    Adequate Bone Marrow Function Defined as:

    • Peripheral absolute neutrophil count (ANC) ≥1000/mm3
    • Platelet count ≥100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
    • Hemoglobin >8 g/dL (may be transfused)

    Adequate Renal Function Defined as:

    • Creatinine clearance or radioisotope GFR > 70ml/min/1.73 m2 or

    • A serum creatinine based on (Schwartz et al. J. Peds, 106:522, 1985) age/gender as follows:

      1. to < 2 years: maximum serum creatinine 0.6 mg/dL for males and females. 2 to < 6 years: maximum serum creatinine 0.8 mg/dL for males and females. 6 to < 10 years: maximum serum creatinine 1.0 mg/dL for males and females. 10 to < 13 years: maximum serum creatinine 1.2 mg/dL for males and females. 13 to < 16 years: maximum serum creatinine 1.5 mg/dL for males and 1.4 mg/dL for females. ≥ 16 years: maximum serum creatinine 1.7 mg/dL for males and 1.4 mg/dL for females.

    Adequate Liver Function Defined as:

    • Total bilirubin ≤ 1.5 × institutional upper limit of normal
    • AST (SGOT) ≤ 2.5 × institutional upper limit of normal
    • ALT (SGPT) ≤ 2.5 × institutional upper limit of normal

    Adequate Cardiac Function Defined as:

    • Left Ventricular Ejection Fraction greater than the institutional lower limit of normal by echocardiogram
    • QTc ≤ 480 msec (by Bazett formula)

    Adequate Neurologic Function Defined as:

    • Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment.
    • Patients with current seizure disorders may be enrolled if seizures are well-controlled on antiepileptic therapies.
  7. Informed Consent: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines

Exclusion Criteria:

  1. Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to unknown risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for at least 90 days after discontinuation of drug for females and at least 60 days for males. For females of childbearing potential, agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods (bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices; hormonal contraceptive methods must be supplemented by a barrier method) and agreement to refrain from donating eggs are required. For males of reproductive potential, agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm.

  2. Gastrointestinal Disease:

    • Patients with a history of serious gastrointestinal disease, including inflammatory bowel disease or gastrointestinal perforation
    • Patients who are unable to absorb enteral medications
    • Administration via NG/NJ/G-tube is allowed

  3. Concomitant Medications

    • Corticosteroids: Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible.
    • Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible.
    • Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible.

  4. Study Specific:

    • Patients who have an uncontrolled infection are not eligible.
    • Patients who have received any live or attenuated vaccinations within three months prior to start of therapy are not eligible.
    • Any significant concurrent medical or surgical condition that would jeopardize the patient's safety or ability to complete the study, including, but not limited to, disease of the nervous, renal, hepatic, cardiac (such as symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia), pulmonary, or endocrine system
    • Patients who have a history of Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus or Tuberculosis infection are not eligible.
    • Patients who have received a prior solid organ transplantation are not eligible.
    • Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
    • Patients who have a history of alcohol, drug, or chemical abuse within 6 months of screening.
    • Patients who have had surgery within the last 6 weeks or who have concerns for poor postsurgical wound healing.
    • Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to tocilizumab and its excipients are not eligible.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Stratum 1 and Stratum 2

Stratum 1: Patients with progressive or recurrent adamantinomatous craniopharyngiomas following radiation therapy.

Stratum 2 (NOT CURRENTLY ENROLLING): Patients with measurable adamantinomatous craniopharyngioma who have undergone surgery but have not previously received radiation therapy. Progressive disease is allowed but not required
Drug: Binimetinib Oral Tablet [Mektovi]
Binimetinib oral continuous dosing 32 mg/m2 PO BID for 4 weeks
Other Names:
  • MEKTOVI

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sustained objective response rate of patients with recurrent/progressive previously irradiated ACP to treatment with oral binimetinib
Time Frame: From Day 1 of treatment through 30 days following end of protocol treatment
To calculate the number of patients who experience sustained objective response rate [minor response (MR) + partial response (PR) + complete response (CR)] of patients with recurrent/progressive previously irradiated Adamantinomatous Craniopharyngioma to treatment with oral binimetinib (Stratum 1).
From Day 1 of treatment through 30 days following end of protocol treatment
Sustained objective response rate of patients with measurable ACP who have undergone surgery but have not been previously treated with radiation to treatment with oral binimetinib
Time Frame: From Day 1 of treatment through 30 days following end of protocol treatment
To calculate the number of patients who experience sustained objective response rate (MR + PR + CR) of patients with measurable Adamantinomatous Craniopharyngioma who have undergone surgery but have not been previously treated with radiation to treatment with oral binimetinib (Stratum 2).
From Day 1 of treatment through 30 days following end of protocol treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Toxicities associated with tocilizumab in children with ACP
Time Frame: 24 months
To calculate the number of participants with, as well as frequency and severity of, binimetinib-related Adverse Events as assessed by CTCAE v5.0 in children with recurrent or refractory ACP
24 months
PFS of ACP patients treated with binimetinib after radiation
Time Frame: 12 months
To assess one-year progression-free survival (PFS) rates for patients with ACP who are treated with binimetinib following progression after radiation (Stratum 1).
12 months
PFS of ACP patients treated with binimetinib who have not received radiation
Time Frame: 12 months
To assess one-year progression-free survival (PFS) rates for patients with ACP who are treated with binimetinib who have not previously received radiation (Stratum 2).
12 months
Biological effects of binimetinib on ACP tumor tissue and cyst fluid.
Time Frame: From Day 1 of treatment through 30 days following end of protocol treatment
To measure concentrations of various chemokines including IL-6, IL-8, IL-10 and CXCL1in cyst fluid or tumor or blood of ACP patients treated with binimetinib. Comparisons will be made with known levels in the literature and among patient samples from within the study.
From Day 1 of treatment through 30 days following end of protocol treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nationwide Children's Hospital

Collaborators

Children's Hospital Colorado

Investigators

  • Study Chair: Todd C Hankinson, MD, Children's Hospital Colorado
  • Principal Investigator: Maryam Fouladi, MD, Nationwide Children's Hospital
  • Study Chair: Holly Lindsay, MD, Children's Hospital Colorado

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 10, 2023

Primary Completion (Estimated)

April 10, 2027

Study Completion (Estimated)

April 10, 2027

Study Registration Dates

First Submitted

March 1, 2022

First Submitted That Met QC Criteria

March 9, 2022

First Posted (Actual)

March 18, 2022

Study Record Updates

Last Update Posted (Actual)

April 8, 2026

Last Update Submitted That Met QC Criteria

April 3, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CONNECT2108

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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