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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
57
Given orally
University of Alabama at Birmingham
Birmingham, Alabama, United States
RECRUITINGProgression free survival rate (PFS)
Progression-free survival is defined as the time of documented response until disease progression as defined by Response assessment in neuro-oncology criteria (RANO) criteria. PFS will be reported by overall group at 12 months.
Time frame: Up to 12 months
Changes in scores on the Physical functioning subscale of the Pediatric Quality of Life Inventory (PedsQL) over time
Scores over time from the PedsQL 4.0 Generic Core physical function domain rating form, which have multidimensional child self-report and parent proxy report scales to assess health-related quality of life (QOL) in children, adolescents, and young adults ages 2 - 25 years will be reported. Physical functioning, is the sub-scale of interest for this protocol. Items on the physical functioning sub-scale are scored on a 5-point Likert scale with raw scores ranging from 0- 4. Items are reversed scored and linearly transformed to a 0-100 scale. If more than 50% of the items in the scale are missing, the Scale Scores should not be computed. Higher scores indicate a higher level of physical functioning
Time frame: Up to 12 months
Proportion of participants with visual deficits over time
Teller acuity testing using Teller Acuity Cards® (TAC) II will be performed on every time participants undergo a radiographic disease assessment. Visual acuity (VA) testing will be performed in each eye separately at a distance of 55 centimeters in all participants. The tester will use the "two down, one up" protocol to achieve the best VA score. Acuity will be reported in logarithm of the minimum angle of resolution (logMAR). Visual field testing will be performed by confrontation and reported as the number of quadrants (0, 1, 2, 3, or 4) with visual field deficits. Optic discs will be assessed for the presence or absence of pallor and edema.The proportion of participants with recorded visual deficits over time based on these assessments will be reported.
Time frame: Up to 5 years
Proportion of participants with neuroendocrine deficits
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Rady Children's Hospital/University of California, San Diego
San Diego, California, United States
RECRUITINGUniversity of California, San Francisco
San Francisco, California, United States
RECRUITINGUniversity of Florida
Gainesville, Florida, United States
RECRUITINGAnn & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States
RECRUITINGRiley Hospital for Children at Indiana University Health
Indianapolis, Indiana, United States
RECRUITINGJohn Hopkins University
Baltimore, Maryland, United States
RECRUITINGDana-Farber/Boston Children's Harvard Medical School
Boston, Massachusetts, United States
RECRUITINGUniversity of Michigan
Ann Arbor, Michigan, United States
RECRUITINGChildren's Minnesota
Minneapolis, Minnesota, United States
RECRUITING...and 7 more locations
The proportion of participants with presence of new neuroendocrine deficits defined as hypothalamic obesity, diabetes insipidus, growth hormone deficiency, adrenal insufficiency from baseline will be reported.
Time frame: Up to 5 years