Table 1.

Clinical trials involving optic pathway glioma that are currently in progress

Trial name Registration number	Primary objective	Trial design	Estimated study completion	Sample size	Patient age	Intervention	Comparison	Primary outcome	Country (primary institution)
Phase 0/I pharmacological trials
Pediatric Neuro-Oncology Consortium (PNOC)-002: Safety, Phase 0, and Pilot Efficacy Study of Vemurafenib, an Oral Inhibitor of BRAFV600E, in Children and Young Adults with Recurrent/Refractory BRAFV600E- or BRAF Ins T Mutant Brain Tumors NCT01748149	Assess safety and establish maximum tolerated and recommended phase II dose of vemurafenib in recurrent or refractory gliomas containing the BRAFV600E or BRAF Ins T mutation	Open label Non-randomised Single group Phase 0/I	December 2020	40	0–25 years	Drug: vemurafenib	Dose escalation	Maximum tolerated dose, toxicity, pharmacokinetics and objective response. Then intratumoural drug concentration	USA (UCSF)
Phase I pharmacological trials
A Phase I Study of TAK-580 (MLN2480) for Children with Low-Grade Gliomas and other RAS/RAF/MEK/ERK Pathway Activated Tumors NCT03429803	Determine safety of treatment and appropriate dosage of TAK-580 in children and adolescent participants with LGG	Open label Non-randomised Single group Phase I	December 2024	53	1–25 years	Drug: TAK-580 (MLN2480)	N/A: safety analysis	Dose-limiting toxicity and progression-free survival	USA (Dana-Farber)
A Phase I Trial of Pomalidomide for Children with Recurrent, Progressive, or Refractory CNS Tumors NCT02415153	Determine best dosage of pomalidomide in treating younger patients with recurrent, progressive or refractory CNS tumours	Open label Non-randomised Single group Phase I	March 2020	42	3–20 years	Drug: pomalidomide	N/A: safety analysis	Maximum tolerated dose and recommended phase II dose, toxicity, pharmacokinetics	USA (NCI)
Sirolimus in Combination with Metronomic Therapy in Children with Recurrent and Refractory Solid Tumors: A Phase I Study NCT01331135	Investigate anti-tumour activity, optimal dosing and toxicity of sirolimus in combination with other chemotherapy in recurrent or refractory solid tumours	Open label Non-randomised Single group Phase I	April 2021	24	0–30 years	Drug: sirolimus	Dose escalation	Maximum tolerated dose and recommended phase II dose	USA (Emory)
Anti-Angiogenic Therapy After Autologous Stem Cell Rescue (ASCR) for Pediatric Solid Tumors NCT01661400	Assess feasibility and safety of using anti-angiogenic drugs after autologous stem cell transplant	Open label Non-randomised Sequential assignment Phase I	February 2020	12	6 months–21 years	Drugs: cyclophosphamide and thalidomide	Control versus cyclophosphamide versus thalidomide	Toxicity and best overall response	USA (WUSM)
Phase I/Ib Trial of Combined 5’Azacytidine and Carboplatin for Recurrent/Refractory Pediatric Brain and Solid Tumors NCT03206021	Determine maximum tolerated dose and initial efficacy of 5′azacytidine in combination with carboplatin	Open label Non-randomised Parallel assignment Phase I	July 2021	54	1–18 years	Drug: 5′azacytidine	Dose escalation then expansion	Maximum tolerated dose and feasibility of treatment	Canada (SickKids)
A Phase Ib Dose Escalation Study of Abemaciclib in Combination with Temozolomide and Irinotecan (Part A) and Abemaciclib in Combination with Temozolomide (Part B) in Pediatric and Young Adult Patients with Relapsed/Refractory Solid Tumors NCT04238819	Determine safety and effectivity of abemaciclib in combination with irinotecan and/or temozolomide	Open label Non-randomised Single group Phase I	February 2022	60	0–18 years	Drug: abemaciclib	Dose escalation then dose expansion	Toxicity, pharmacokinetics and response rate	USA (Eli Lilly)
A Phase 1 Study of Entinostat, an Oral Histone Deacetylase Inhibitor, in Pediatric Patients with Recurrent or Refractory Solid Tumors, Including CNS Tumors and Lymphoma NCT02780804	Determine the maximum tolerated and recommended dose of entinostat in children with recurrent or refractory solid tumours	Open label Non-randomised Single group Phase I	April 2022	36	1–21 years	Drug: entinostat	Dose escalation then dose expansion	Maximum tolerated dose, toxicity and pharmacokinetics	USA (NCI)
A Phase I Study of Mebendazole for the Treatment of Pediatric Gliomas NCT01837862	Determine maximally tolerated dose of mebendazole in combination with vincristine, carboplatin and temozolomide (for LGG) OR bevacizumab and irinotecan (for HGG)	Open label Non-randomised Parallel assignment Phase I	April 2020	36	1–21 years	Drug: mebendazole	Dose escalation then dose expansion	Toxicity and response rate of participants	USA (Janssen)
Phase I/II pharmacological trials
A Phase 1 and Phase II and Re-Treatment Study of AZD6244 for Recurrent or Refractory Pediatric Low Grade Glioma NCT01089101	Phase I: maximum tolerated dose and recommended phase II dose of selumetinib. Phase II: objective response and disease stabilisation rates with selumetinib treatment	Open label Non-randomised Single group Phase I/II	December 2020	180	3–21 years	Drug: selumetinib (AZD6244)	Dose escalation then dose expansion	Toxicity and response rate of participants	USA (NCI)
Phase I/II Trial of Dabrafenib, Trametinib, and Hydroxychloroquine (HCQ) for BRAF V600E-mutant or Trametinib and HCQ for BRAF Fusion/Duplication Positive or NF1-associated Recurrent or Progressive Gliomas in Children and Young Adults NCT04201457	Phase I: maximum tolerated and recommended phase II dose of HCQ with dabrafenib and/or trametinib in young patients with recurrent or progressive glioma Phase II: response rate	Open label Non-randomised Parallel assignment Phase I/II	February 2025	75	1–30 years	Drug: hydroxychloroquine	Dose escalation then dose expansion	Maximum tolerated dose and response rate	USA (PBTC)
A Phase 2 Study of Trametinib for Patients with Pediatric Glioma or Plexiform Neurofibroma With Refractory Tumor and Activation of the MAPK/ERK Pathway. NCT03363217	Asses response rate of paediatric glioma and plexiform neurofibroma (PN) to trametinib	Open label Non-randomised Parallel assignment Phase I/II	June 2026	150	1 month–25 years	Drug: trametinib	N/A	Objective response rate	Canada (St Justine’s Hospital)
An Open-Label, Dose-Escalation, Phase I/II Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of the MEK Inhibitor Trametinib in Children and Adolescents Subjects with Cancer or Plexiform Neurofibromas and Trametinib in Combination with Dabrafenib in Children and Adolescents with Cancers Harboring V600 Mutations NCT02124772	Establish safe dose and effectivity of trametinib monotherapy and in combination with dabrafenib in young patients	Open label Non-randomised Sequential assignment Phase I/II	December 2020	142	1 month–17 years	Drug: trametinib	Dose escalation	Safe dose, toxicity and response rate	USA (Novartis)
A Phase 1/2 Study of Lenvatinib in Combination with Everolimus in Recurrent and Refractory Pediatric Solid Tumors, Including CNS Tumors NCT03245151	Determine safety, optimal dose and response rate of lenvatinib combined with everolimus in paediatric patients with recurrent/refractory solid tumours	Open label Non-randomised Parallel assignment Phase I/II	May 2022	120	2–21 years	Drug: lenvatinib	Dose escalation then dose expansion	Maximum tolerated dose, recommended phase II dose, toxicity and response rate	USA (Eisai Inc)
A Paediatric Phase I/II Study of Intermittent Dosing of The Mek-1 Inhibitor Selumetinib In Children with Neurofibromatosis Type-1 And Inoperable Plexiform Neurofibroma and/or Progressive Optic Pathway Glioma Intermittent Dosing of Selumetinib in Childhood NF1 Associated Tumours (INSPECT) NCT03326388	Phase I: evaluate maximum tolerated dose of selumetinib Phase II: response rate to selumetinib in NF1 inoperable plexiform neurofibroma and OPG	Open label Non-randomised Single group Phase I/II	December 2023	30	3–18 years	Drug: selumetinib	Dose escalation	Response rate of participants measured with 3D volumetric analysis/2D assessment of tumour size	UK (GOSH)
Phase I Study of MEK162 for Children with Progressive or Recurrent Cancer and a Phase II Study for Children with Low-Grade Gliomas and other Ras/Raf/MAP Pathway Activated Tumors NCT02285439	Phase I: determine best dose and safety of MEK162 in children and adolescents Phase II: define response rate	Open label Non-randomised Parallel assignment Phase I/II	January 2021	120	1–18 years	Drug: MEK162	Dose escalation	Maximum tolerated dose and response rate	USA (CHLA)
Phase II pharmacological trials
A Phase II, Open-Labeled, Multi-Center, Randomized Controlled Trial of Vinblastine +/- Bevacizumab for the Treatment of Chemotherapy-Naïve Children with Unresectable or Progressive Low-Grade Glioma (LGG) NCT02840409	Determine efficacy of adding bevacizumab to vinblastine in chemotherapy-naïve paediatric patients with progressive/unresectable LGG	Open label Randomised Parallel assignment Phase II	August 2026	150	6 months–18 years	Drug: bevacizumab	Vinblastine versus vinblastine plus bevacizumab	Response rate	Canada (SickKids)
Phase II Open-label Global Study to Evaluate the Effect of Dabrafenib in Combination with Trametinib in Children and Adolescent Patients with BRAF V600 Mutation Positive Low Grade Glioma (LGG) or Relapsed or Refractory High Grade Glioma (HGG) NCT02684058	Investigate effect of dabrafenib combined with trametinib in young patients with LGG BRAF V600 positive or relapsed or refractory HGG	Open label Non-randomised Single group Phase II	November 2021	142	1–17 years	Drug: dabrafenib	Dabrafenib and trametinib versus carboplatin and vincristine	Overall response rate	USA (Novartis)
NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) - Phase 2 Subprotocol of BVD-523FB (Ulixertinib) in Patients with Tumors Harboring Activating MAPK Pathway Mutations NCT03698994	Assess efficacy of ulixertinib in patients with mutations in the MAPK signalling pathway	Open label Non-randomised Single group Phase II	December 2025	49	1–21 years	Drug: ulixertinib	N/A	Objective response rate	USA (NCI)
Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors: A Pilot Study NCT03194906	Estimate participation rate in a study of memantine as a neuroprotective agent, rate of medication adherence and completion of cognitive assessments	Double blind Randomised Placebo controlled Parallel assignment Phase II	January 2021	50	6–21 years	Drug: memantine	Memantine versus placebo	Percentage who participate, complete 12 weeks of therapy and a minimum of 3 cognitive assessments	USA (St. Jude)
Phase II Study of Everolimus for Recurrent or Progressive Low-grade Gliomas in Children NCT01734512	Determine efficacy of everolimus in children with recurrent or progressive LGG	Open label Non-randomised Single group Phase II	January 2028	66	3–21 years	Drug: everolimus	N/A	Progression-free survival	USA (UCSF)
A Phase II Trial of Poly-ICLC in the Management of Recurrent Pediatric Low Grade Gliomas NCT01188096	Determine safety and effectivity of poly-ICLC in young patients with LGG	Open label Non-randomised Single group Phase II	July 2019	23	0–21 years	Drug: poly-ICLC	N/A	Overall response rate	USA (UCSD)
Pilot Study of the MEK1/2 Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) for Adults with Neurofibromatosis Type 1 (NF1) and Cutaneous Neurofibromas (CNF) NCT02839720	Establish if selumetinib can result in volume decrease of cutaneous neurofibromas	Open label Non-randomised Single group Phase II	December 2021	24	18+ years	Drug: selumetinib	N/A	Change in tumour size	USA (NCI)
A Phase II Study of Pegylated Interferon alfa-2b in Children with Recurrent or Refractory and Radiographically or Clinically Progressive Juvenile Pilocytic Astrocytomas & Optic Pathway Gliomas NCT02343224	Response rate to pegylated interferon	Open label Non-randomised Single group Phase II	December 2021	20	3–25 years	Drug: pegylated interferon alfa-2b	N/A	Response rate of participants from baseline to 2 years	USA (Emory)
A Phase II Randomized Trial of Lenalidomide (NSC # 703813) in Pediatric Patients with Recurrent, Refractory or Progressive Juvenile Pilocytic Astrocytomas and Optic Pathway Gliomas NCT01553149	Response rate (complete or partial) to low- or high-dose lenalidomide	Open label Randomised Parallel assignment Phase II	June 2020	80	0–21 years	Drug: lenalidomide	Low-dose or high-dose lenalidomide	Objective best response rate	USA (NCI)
Phase III pharmacological trials
A Phase 3 Randomized Study of Selumetinib Versus Carboplatin/Vincristine in Newly Diagnosed or Previously Untreated Neurofibromatosis Type 1 (NF1) Associated Low-Grade Glioma NCT03871257	Assess selumetinib compared with treatment with carboplatin/vincristine (CV) for participants with NF1-associated low-grade glioma, and to assess if selumetinib is better than CV in improving vision in participants with LGG of the optic pathway	Open label Randomised Parallel assignment Phase III	May 2027	290	2–21 years	Drug: selumetinib	Selumetinib versus carboplatin and vincristine	Event-free survival and number of participants with visual improvement	USA (NCI)
A Phase 3 Randomized Non-Inferiority Study of Carboplatin and Vincristine Versus Selumetinib (NSC# 748727) in Newly Diagnosed or Previously Untreated Low-Grade Glioma (LGG) Not Associated with BRAFV600E Mutations or Systemic Neurofibromatosis NCT04166409	Determine efficacy of treatment with selumetinib compared with carboplatin and vincristine in untreated LGG (not NF1 or BRAFV600E associated)	Open label Randomised Parallel assignment Phase III	December 2026	200	2–12 years	Drug: selumetinib	Selumetinib versus carboplatin and vincristine	Event-free survival	USA (NCI)
Biological therapy trials
A Phase I Study of Ad-RTS-hIL-12, an Inducible Adenoviral Vector Engineered to Express hIL-12 in the Presence of the Activator Ligand Veledimex in Pediatric Brain Tumor Subjects NCT03330197	Assess safety and tolerability of intratumoural Ad-RTS-hIL-12 injection in combination with oral veledimex	Open label Non-randomised Sequential single groups Phase I	March 2021	24	0–21 years	Biological: Ad-RTS-hIL-12	N/A: safety analysis	Dose-limiting toxicity and safety of treatment	USA (Ziopharm)
Phase 1 Study of B7-H3-Specific CAR T Cell Locoregional Immunotherapy for Diffuse Intrinsic Pontine Glioma/Diffuse Midline Glioma and Recurrent or Refractory Pediatric Central Nervous System Tumors NCT04185038	Assess safety and feasibility of B7H3-specific CAR T cell administration via indwelling catheter into the tumour resection cavity or ventricular system in DIPG, DMG and recurrent or refractory CNS tumours	Open label Non-randomised Parallel assignment Phase I	May 2041	70	1–26 years	Biological: B7H3-specific CAR T cell	N/A: safety analysis	Successful delivery, toxicity and response rate	USA (Seattle Children’s)
Radiotherapy-based trials
A Phase II Study of Proton Radiotherapy for Pediatric Brain Tumors Requiring Partial Brain Irradiation: An Assessment of Long Term Neurocognitive, Neuroendocrine an Ototoxicity Outcomes NCT01288235	Determine if proton radiotherapy has reduced long-term neuroendocrine and neurocognitive impact compared with standard radiation	Open label Non-randomised Single group Phase II	September 2022	100	1–25 years	Radiation: proton radiotherapy	Standard radiation versus proton radiotherapy	Endocrine dysfunction and neurocognitive sequelae	USA (MGH)
A Phase II Study of Hippocampal-Avoidance Using Proton Therapy in Low-Grade Glioma NCT04065776	Determine feasibility of reducing radiation therapy doses to the hippocampi using proton therapy	Open label Non-randomised Single group Phase II	May 2023	74	6–21 years	Radiation: hippocampal-avoidance proton therapy	N/A	Percentage of plans meeting first or second dose constraints	USA (St. Jude)
Diagnostic imaging trials
Developing Fast Pediatric Imaging NCT03761121	Development of improved MRI technologies to better measure brain tumour tissue volume	Open label Non-randomised Parallel assignment	September 2021	300	All	Other: Wave-CAIPI (controlled aliasing in parallel imaging)	N/A	Validation of Wave-CAIPI as a diagnostic tool	USA (Dana-Farber)
Pilot Study of [18F] Fluorodeoxyglucose Positron Emission Tomography- Magnetic Resonance Imaging (FDG-PET-MRI) in CNS and Extra-CNS Tumors of Patients with Neurofibromatosis-1 (NF1) NCT01800032	Acquire preliminary data and report differences in FDG-avidity in patients with NF1-associated optic glioma and plexiform neurofibroma	Observational Prospective cohort study (pilot)	December 2019	30	6+ years	Device: FDG-PET-MRI	Progressive versus non-progressive disease	Comparison of FDG-avidity between progressive and non-progressive lesion/disease	USA (Lineberger Centre)
Miscellaneous trials (genetic, social function, image-guided thermotherapy)
Frameshift Peptides of Children with Neurofibromatosis Type 1 (NF1) and Either Low-Grade Gliomas or Plexiform Neurofibromas NCT04212351	Establish if children and young adults with NF1 and LGGs or plexiform neurofibroma have a specific frameshift peptide profile for potential development of a disease-specific vaccine	Observational Prospective cohort study	April 2021	60	0–30 years	Genetic: frameshift array blood sample test	Active LGG versus plexiform neurofibroma, versus neither	Frameshift peptide protein profile in patients with NF1 and those who develop LGGs versus plexiform neurofibromas	USA (CNRI)
Components of Social Functioning in Survivors of Pediatric Brain Tumors NCT03361033	Observe social and neurocognitive functioning in paediatric survivors of brain tumours	Observational Prospective cohort study	February 2021	80	8–12 years	N/A	N/A	Predictors of social, cognitive and neurocognitive abilities on social interaction	USA (St. Jude)
A Pilot Study of Using MRI-Guided Laser Heat Ablation to Induce Disruption of the Peritumoral Blood Brain Barrier to Enhance Delivery and Efficacy of Treatment of Pediatric Brain Tumors NCT02372409	Assess and establish the window of maximal blood–brain barrier disruption post laser ablation	Open label Non-randomised Parallel assignment Phase I	October 2020	12	3–21 years	Device: MRI-guided laser ablation	MRI-guided laser ablation versus MRI-guided laser ablation plus doxorubicin and etoposide	Progression-free survival, overall survival and quality of life	USA (Washington University)