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MEKTOVI® for the Treatment of Pediatric Adamantinomatous Craniopharyngioma

PHASE2RECRUITING

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 details:

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 \<25 years with measurable ACP who may have been previously treated with radiation (Stratum 1, 18 patients) or without radiation (Stratum 2, 18 patients).

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  1. Patients must be ≥ 12 months and ≤ 25 years of age at the time of study enrollment.
  2. Patients with histologically-confirmed adamantinomatous craniopharyngioma (ACP).
  3. Patients must have measurable disease.
  4. Patients with progressive or recurrent ACP who demonstrate cystic and/or solid recurrence or progression at least 6 months post completion of radiation therapy.
  5. Patients with measurable ACP who have undergone surgery but have NOT previously undergone irradiation.
  6. Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age.
  7. Patients must have recovered or stabilized from the acute toxic effects of prior treatments.
  8. Adequate Bone Marrow Function.
  9. Adequate Renal Function.
  10. Adequate Liver Function.
  11. Adequate Cardiac Function.
  12. Adequate Neurologic Function.
  13. All patients and/or their parents or legally authorized representatives must sign a written informed consent.

Exclusion criteria

  1. Pregnant or breast-feeding women will not be entered on this study.
  2. Patients with a history of serious gastrointestinal disease, including inflammatory bowel disease or gastrointestinal perforation.
  3. Patients who are unable to swallow, retain or absorb oral medications.
  4. 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.
  5. Patients who are currently receiving another investigational drug are not eligible.
  6. Patients who are currently receiving other anti-cancer agents are not eligible.
  7. Patients who have an uncontrolled infection are not eligible.
  8. Patients who have received any live or attenuated vaccinations within three months prior to start of therapy are not eligible.
  9. Any significant concurrent medical or surgical condition that would jeopardize the patient's safety or ability to complete the study.
  10. Patients who have a history of Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus or Tuberculosis infection are not eligible.
  11. Patients who have received a prior solid organ transplantation are not eligible.
  12. 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.
  13. Patients who have a history of alcohol, drug, or chemical abuse within 6 months of screening.
  14. Patients who have had surgery within the last 6 weeks or who have concerns for poor postsurgical wound healing.
  15. 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.

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE2

trial

Study ID

NCT05286788

Intervention or treatment

DRUG: Binimetinib Oral Tablet [Mektovi]

Conditions

  • Adamantinous Craniopharyngioma
  • Recurrent Adamantinomatous Craniopharyngioma

  • Condition: Adamantinous Craniopharyngioma, Recurrent Adamantinomatous Craniopharyngioma

  • DRUG: Binimetinib Oral Tablet [Mektovi]

  • Randwick, New South Wales, Australia and more

  • Sponsor: Nationwide Children's Hospital

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Are you running this trial?

If you're a clinic or sponsor, you can claim this study

Research sites nearby

Closest Location:

Sydney Children's Hospital

Select from list below to view details:

  • Sydney Children's Hospital

    Randwick, New South Wales, Australia

  • Queensland Children's Hospital

    South Brisbane, Queensland, Australia

  • Perth Children's Hospital

    Perth, Western Australia, Australia

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Who is running the clinical trial?

NCH

Nationwide Children's Hospital

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?

Participant Group/ArmIntervention/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]

    What is the study measuring?

    Primary Outcome

    MeasureDescriptionTime Frame
    Sustained objective response rate of patients with recurrent/progressive previously irradiated ACP to treatment with oral binimetinibTo 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 binimetinibTo 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

    MeasureDescriptionTime Frame
    Biological effects of binimetinib on ACP tumor tissue and cyst fluid.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
    Toxicities associated with tocilizumab in children with ACPTo 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 ACP24 months
    PFS of ACP patients treated with binimetinib after radiationTo 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 radiationTo 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
    Are you running this trial?If you're a clinic or sponsor, you can claim this study.
    Claim this trial

    References

    Clinical Trials Gov: MEKTOVI® for the Treatment of Pediatric Adamantinomatous Craniopharyngioma

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