Tovorafenib for Treatment of Craniopharyngioma in Children and Young Adults
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age1-39
SponsorSabine Mueller, MD, PhD
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Newly diagnosed craniopharyngioma, as based on imaging characteristics and central radiology review. Participants will initially be screened within confines of a screening consent and only those participants with findings consistent with craniopharyngioma and without findings suggesting an indeterminate lesion or lesion of an alternative diagnosis (including abnormal tumor markers found in blood or cerebral spinal fluid (CSF), if completed as part of standard of care (SOC) work-up or if lesion concerning for alternate diagnosis) will move ahead with enrollment on the treatment protocol. Additionally, for participants that have undergone initial biopsy to confirm diagnosis, are within 6 weeks of radiographic diagnosis, and are planned to undergo follow up second surgery for additional tumor resection as per standard of care recommendations, these participants will also be considered eligible.
Participants must be surgical candidates for biopsy or resection and planned for standard of care biopsy or resection.
Recurrent craniopharyngioma, as based on histologic confirmation at time of initial diagnosis (participants with Adamantinomatous craniopharyngioma (ACP) will only be eligible for the recurrent arm).
Recurrent craniopharyngioma without prior histologic confirmation will initially be screened within confines of a screening consent and only those participants with findings consistent with craniopharyngioma and without findings suggesting an indeterminate lesion or lesion of an alternative diagnosis (including abnormal tumor markers found in blood or CSF, if completed as part of SOC work-up or if lesion concerning for alternate diagnosis) will move ahead with enrollment on the treatment protocol.
Disqualifiers
Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from acute adverse events due to agents administered more than 4 weeks earlier.
Participants must be at least 1 week since the completion of therapy with a biologic or small molecule agent. For any agent with known adverse events that can occur beyond 1 week after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur. Such participants should also be discussed with study chairs.
Participants should not have previously received any RAS-pathway, but have not received Tovorafenib will be eligible.
Rapidly progressive symptoms that require urgent surgery or radiation therapy, which would prevent central review and or preclude participation with tumor-directed medical management alone.
Trial design
Design model
Parallel
Treatments tested in this trial
Tovorafenib
DrugGiven orally
Treatment groups
57 Participants
are divided into 3 treatment groupsGroup A: Group 1: Neoadjuvant TovorafenibExperimental treatment 1 intervention
Group B: Group 2, Arm A: Neoadjuvant TovorafenibExperimental treatment 1 intervention
Group C: Group 2, Arm B: Non-biopsy/resection participantsExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Progression 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 months2
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 monthsSecondary outcomes
1
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 years2
Proportion of participants with neuroendocrine deficits
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 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Sabine Mueller, MD, PhD
Lead sponsor
University of California, San Francisco
Sponsor institution
Day One Biopharmaceuticals, Inc.
Collaborator
Source ClinicalTrials.gov