NCT05465174

Tovorafenib for Treatment of Craniopharyngioma in Children and Young Adults

Tovorafenib for the Treatment of Newly Diagnosed or Recurrent Craniopharyngioma in Children and Young Adults

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 57 (estimated)
• Sponsor: Sabine Mueller, MD, PhD · Academic / Other
• Sex: All
• Age: 1 Year – 39 Years
• Healthy volunteers: Not accepted

Summary

The current study assesses the tolerability and efficacy of monotherapy with pan-RAF-kinase (Tovorafenib) inhibition for the treatment of children and young adults with craniopharyngioma.

Detailed description

PRIMARY OBJECTIVE: I. To determine progression free survival and maintenance of quality of life at 12 months as based on physical function and compared to historical controls. SECONDARY OBJECTIVES: I. To identify proportion of participants with visual deficits at 1-year, 2-year, and 3-year follow-up. II. To identify proportion of participants with neuroendocrine deficits at 1-year, 2-year, and 3-year follow-up. EXPLORATORY OBJECTIVES: I. To assess Quality of Life (QOL) and cognitive measures in children and young adults with newly diagnosed or recurrent craniopharyngioma. II. To perform Immunohistochemistry (IHC)/Multiplexed ion beam imaging on pre-and post-treatment tumor tissue (as available), including at time of progression, to assess for patterns of protein density and spatial relationship in intact tumor tissue and elucidate changes in tumor tissue over the course of therapy and disease evolution. III. To perform single-cell (scRNA) RNA sequencing on pre- and post-treatment tumor tissue (as available), including at time of progression, to identify and characterize distinct cell subsets that make up the components of craniopharyngioma and elucidate changes in cell subsets over the course of therapy and disease evolution. IV. To perform proteomic analysis on pre- and post-treatment tumor tissue, including at time of progression, to characterize distinct proteins and transcriptome pathways that are active in different tumor compartments and elucidate changes in proteomic profiles over the course of therapy and disease evolution. V. To perform ELISA array/multiplex analysis on pre- and post-treatment cyst fluid, including at time of progression, to characterize distinct cytokine profiles and elucidate changes in cytokine profile over the course of therapy and disease evolution. VI. Microbiome and flow cytometry studies in the context of imaging and clinical outcomes using descriptive statistics. VII. To assess patient and/or proxy satisfaction with study participation via patient-reported outcome (PRO) measures. VIII. To assess patient and/or proxy satisfaction with study participation via patient-reported outcome (PRO) measures in the context of race ethnicity and other health related social risks. IX. To assess on therapy toxicity in the context of race, ethnicity and other health related social risks. TREATMENT GROUPS: Participants will be divided into 2 cohorts: newly diagnosed or recurrent craniopharyngioma, both planned for standard of care biopsy/resection. All newly diagnosed participants or recurrent craniopharyngioma without histologic diagnosis will be enrolled on a screening consent for central imaging review to ensure imaging supports diagnosis of craniopharyngioma before enrollment onto the treatment protocol. After enrollment onto treatment protocol, each patient in each arm will receive one dose of tovorafenib prior to planned biopsy or resection. Participants with measurable disease will then continue on maintenance therapy. Participants who have a gross total resection (GTR) will enter into the follow-up only phase.

Conditions

• Craniopharyngioma, Child
• Craniopharyngioma
• Recurrent Craniopharyngioma

Interventions

Type	Name	Description
DRUG	Tovorafenib	Given orally

Timeline

• Start date: 2022-09-12
• Primary completion: 2027-03-01
• Completion: 2028-03-01
• First posted: 2022-07-19
• Last updated: 2026-03-09

Locations

19 sites across 2 countries: United States, Australia

Regulatory

• FDA-regulated drug study