Symptoms and General Pathology

All Conditions

Neoplasms

Musculoskeletal Diseases

Rare Diseases

Recurrence

Craniopharyngioma

Adamantinoma

Ameloblastoma

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Bone Neoplasms

Bone Diseases

Neuroepithelioma

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 oral continuous dosing 32 mg/m2 PO BID for 4 weeks

Binimetinib Oral Tablet [Mektovi]

Leonie Mikael

Kathleen Dorris, MD

Eugene Hwang, MD

Ashley Plant, MD

Susan Chi, MD

David H Ashley

Peter de Blank, MD

Maryam Fouladi, MD

Patricia Baxter, MD

Sarah Leary, MD

Neevika Manoharan, MBBS

Tim Hassall, MBBS

Santosh Valvi, MBBS

Eric Bouffet, MD

Genevieve Legault, MD

Olaf Witt, MD

Jasper van der Lugt, MD, PhD

Darren Hargrave, MD

Kathleen H Dorris

Todd C Hankinson

Maryam Fouladi

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.

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).

MEKTOVI® for the Treatment of Pediatric Adamantinomatous Craniopharyngioma

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

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).

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).

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.

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

To assess one-year progression-free survival (PFS) rates for patients with ACP who are treated with binimetinib following progression after radiation (Stratum 1).

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).

Children's Hospital Colorado

Nationwide Children's Hospital

Spots Global Cancer Trial Database for binimetinib oral tablet [mektovi]