Symptoms and General Pathology

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Craniopharyngioma

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Neuroectodermal Tumors, Primitive

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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

For \< 30 kg: 12 mg/kg IV every 2 weeks; For ≥30 kg: 8 mg/kg IV every 2 weeks

Tocilizumab

Leonie Mikael, PhD

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

Rebecca Ronsley, MD

Neevika Manoharan, MBBS

Tim Hassall, MBBS

Santosh Valvi, MBChB

Eric Bouffet, MD

Genevieve Legault, MD

Olaf Witt, MD

Jasper van der Lugt, MD, PhD

Darren Hargrave, MD

Kathleen H Dorris, MD

Todd C Hankinson, MD

ACTEMRA (tocilizumab) is an IL-6 receptor antagonist used for the treatment of adult Rheumatoid Arthritis as well as Polyarticular (PJIA) and Systemic (SJIA) Juvenile Idiopathic Arthritis. 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 IL-6 pathway blockers may have efficacy in the control of ACP. We hypothesize that the IL6- receptor antagonist ACTEMRA (tocilizumab) will be safe and effective at inducing tumor response in children with residual ACP.

In this study, up to 38 patients will receive tocilizumab at the dose approved for pediatric Systemic Juvenile Idiopathic Arthritis (\< 30 kg: 12 mg/kg IV every 2 weeks; ≥30 kg: 8 mg/kg IV every 2 weeks). Therapy 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 unresectable ACP who may have been previously treated with radiation (Stratum 1, 18 patients) or without radiation (Stratum 2, 18 patients).

ACTEMRA® for the Treatment of Pediatric Adamantinomatous Craniopharyngioma

Phase 2 Study of Systemic IL-6 Receptor Antagonist ACTEMRA® (Tocilizumab) for the Treatment of Progressive/Recurrent 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 systemic tocilizumab (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 systemic tocilizumab (Stratum 2).

To measure the concentrations of IL-6, IL-8, IL-10, CXCL1, CXCR2, IDO-1 and IL-6R using a combination of ELISA, RNAseq, immunohistochemistry and immunofluorescence in cyst fluid or tumor tissue or blood. 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, tocilizumab-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 tocilizumab following progression after radiation (Stratum 1).

To assess one-year progression-free survival (PFS) rates for patients with ACP who are treated with tocilizumab who have not previously received radiation (Stratum 2).

Children's Hospital Colorado

Nationwide Children's Hospital

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

Binimetinib Oral Tablet [Mektovi]

Leonie Mikael

Sarah Leary, MD

Santosh Valvi, MBBS

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).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
ACTEMRA® for the Treatment of Pediatric Adamantinomatous Craniopharyngioma	NCT05233397	Adamantinomatou... Recurrent Adama...	Tocilizumab	1 Year - 25 Years	Nationwide Children's Hospital
MEKTOVI® for the Treatment of Pediatric Adamantinomatous Craniopharyngioma	NCT05286788	Adamantinous Cr... Recurrent Adama...	Binimetinib Ora...	1 Year - 25 Years	Nationwide Children's Hospital

Spots Global Cancer Trial Database for recurrent adamantinomatous craniopharyngioma