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Study Description

MEKTOVI (binimetinib) is a medicine taken by mouth that helps block certain signals in the body that make some tumors grow. In this Phase II study, the drug will be used to treat children diagnosed with Adamantinomatous Craniopharyngioma (ACP), a type of brain tumor. This tumor can be very challenging to treat, and current options like surgery and radiation can affect the patient's quality of life, especially when the tumor comes back.

Recent research shows that ACP might respond to medicines like binimetinib that block specific pathways in the body.

Up to 38 children will take binimetinib in pill form, twice a day for 4 weeks (1 cycle), and treatment could continue for up to two years. The trial will include children aged 1 to 25, some of whom have already had radiation therapy.

The goal is to see if this medicine can help control the tumor and improve their quality of life.

Inclusion Criteria

• Patients must be between 1 and 25 years old.
• Must have a confirmed Adamantinomatous Craniopharyngioma (ACP), either from a solid tumor or cyst fluid.
• Must have a measurable tumor that can be seen on scans:
  • Stratum 1: Patients whose tumor came back or got worse at least 6 months after finishing radiation therapy.
  • Stratum 2: Patients who have had surgery but have not had radiation (they may have had other treatments before).
• Patients must be able to do at least half of their usual activities, even if they use a wheelchair.
• Must have recovered from any side effects of previous treatments.
• Previous Treatments:
  • At least 7 days since the last dose of any biologic treatment (anti-tumor therapy).
  • At least 42 days since any immunotherapy (e.g. cancer vaccines).
  • At least 21 days since a monoclonal antibody treatment.
  • At least 6 months since focused radiation and no history of radiation to the whole brain/spine.
  • Corticosteroids: If on dexamethasone, the dose must be stable or reducing for at least 1 week.
  • Chemotherapy: At least 21 days since the last round of chemotherapy.
  • Surgery: At least 6 weeks since any surgery.
• Blood counts and organ function requirements must meet certain safety levels before treatment.
• Patient and/or their parent/guardian must agree to join the study by signing a consent form.

Additional inclusion and exclusion criteria may apply and will be discussed with you by the study team. 

Publications

• Foreman NK, Faestel PM, Pearson J, Disabato J, Poole M, Wilkening G, Arenson EB, Greffe B, Thorne R. Health status in 52 long-term survivors of pediatric brain tumors. J Neurooncol. 1999 Jan;41(1):47-53. doi: 10.1023/a:1006145724500.
• Goldman S, Pollack IF, Jakacki RI, Billups CA, Poussaint TY, Adesina AM, Panigrahy A, Parsons DW, Broniscer A, Robinson GW, Robison NJ, Partap S, Kilburn LB, Onar-Thomas A, Dunkel IJ, Fouladi M. Phase II study of peginterferon alpha-2b for patients with unresectable or recurrent craniopharyngiomas: a Pediatric Brain Tumor Consortium report. Neuro Oncol. 2020 Nov 26;22(11):1696-1704. doi: 10.1093/neuonc/noaa119.
• Apps JR, Carreno G, Gonzalez-Meljem JM, Haston S, Guiho R, Cooper JE, Manshaei S, Jani N, Holsken A, Pettorini B, Beynon RJ, Simpson DM, Fraser HC, Hong Y, Hallang S, Stone TJ, Virasami A, Donson AM, Jones D, Aquilina K, Spoudeas H, Joshi AR, Grundy R, Storer LCD, Korbonits M, Hilton DA, Tossell K, Thavaraj S, Ungless MA, Gil J, Buslei R, Hankinson T, Hargrave D, Goding C, Andoniadou CL, Brogan P, Jacques TS, Williams HJ, Martinez-Barbera JP. Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK/ERK pathway as a novel therapeutic target. Acta Neuropathol. 2018 May;135(5):757-777. doi: 10.1007/s00401-018-1830-2. Epub 2018 Mar 14.
• Haston S, Pozzi S, Carreno G, Manshaei S, Panousopoulos L, Gonzalez-Meljem JM, Apps JR, Virasami A, Thavaraj S, Gutteridge A, Forshew T, Marais R, Brandner S, Jacques TS, Andoniadou CL, Martinez-Barbera JP. MAPK pathway control of stem cell proliferation and differentiation in the embryonic pituitary provides insights into the pathogenesis of papillary craniopharyngioma. Development. 2017 Jun 15;144(12):2141-2152. doi: 10.1242/dev.150490. Epub 2017 May 15.
• Bendell JC, Javle M, Bekaii-Saab TS, Finn RS, Wainberg ZA, Laheru DA, Weekes CD, Tan BR, Khan GN, Zalupski MM, Infante JR, Jones S, Papadopoulos KP, Tolcher AW, Chavira RE, Christy-Bittel JL, Barrett E, Patnaik A. A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor. Br J Cancer. 2017 Feb 28;116(5):575-583. doi: 10.1038/bjc.2017.10. Epub 2017 Feb 2.
• Watanabe K, Otsu S, Hirashima Y, Morinaga R, Nishikawa K, Hisamatsu Y, Shimokata T, Inada-Inoue M, Shibata T, Takeuchi H, Watanabe T, Tokushige K, Maacke H, Shiaro K, Ando Y. A phase I study of binimetinib (MEK162) in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2016 Jun;77(6):1157-64. doi: 10.1007/s00280-016-3019-5. Epub 2016 Apr 12.
• Patel K, Allen J, Zagzag D, Wisoff J, Radmanesh A, Gindin T, Nicolaides T. Radiologic response to MEK inhibition in a patient with a WNT-activated craniopharyngioma. Pediatr Blood Cancer. 2021 Mar;68(3):e28753. doi: 10.1002/pbc.28753. Epub 2020 Oct 19. No abstract available.