Nivolumab and Tovorafenib for Treatment of Craniopharyngioma in Children and Young Adults (PNOC029)
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ClinicalTrials.gov Identifier: NCT05465174 |
Recruitment Status :
Recruiting
First Posted : July 19, 2022
Last Update Posted : March 29, 2024
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Tracking Information | |||||||
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First Submitted Date ICMJE | July 15, 2022 | ||||||
First Posted Date ICMJE | July 19, 2022 | ||||||
Last Update Posted Date | March 29, 2024 | ||||||
Actual Study Start Date ICMJE | September 12, 2022 | ||||||
Estimated Primary Completion Date | March 1, 2027 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | ||||||
Change History | |||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | Nivolumab and Tovorafenib for Treatment of Craniopharyngioma in Children and Young Adults | ||||||
Official Title ICMJE | Nivolumab and Tovorafenib for the Treatment of Newly Diagnosed or Recurrent Craniopharyngioma in Children and Young Adults | ||||||
Brief Summary | The current study assesses the tolerability and efficacy of combination therapy with PD-1 (nivolumab) and 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 statistic. 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 Groups (newly diagnosed craniopharyngioma, recurrent craniopharyngioma without histological diagnosis) with 3 treatment arms within each group (Neoadjuvant nivolumab, Neoadjuvant Tovorafenib, Neoadjuvant combination nivolumab plus Tovorafenib). There will also be a separate Non-biopsy/resection arm within the Recurrent Craniopharyngioma group. Participants will be randomized in a 1:1:1 and will receive one dose of assigned drug prior to planned biopsy or resection. Participants with measurable disease will then continue on combination maintenance therapy. Participants may continue treatment for up to 24 months total and will be followed up for 3 years after enrollment into the study. |
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Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 2 | ||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Recruiting | ||||||
Estimated Enrollment ICMJE |
56 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Estimated Study Completion Date ICMJE | March 1, 2028 | ||||||
Estimated Primary Completion Date | March 1, 2027 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE | Inclusion Criteria: Newly Diagnosed Participants:
Recurrent Participants:
Radiation:
All Participants:
Exclusion Criteria: Newly Diagnosed Participants: - Participants should not have undergone any previous tumor-directed therapy. Recurrent Participants:
All Participants:
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Sex/Gender ICMJE |
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Ages ICMJE | 1 Year to 39 Years (Child, Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United States | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT05465174 | ||||||
Other Study ID Numbers ICMJE | 210828 NCI-2022-05356 ( Registry Identifier: NCI Clinical Trials Reporting Program (CTRP) ) |
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Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | Sabine Mueller, MD, PhD, University of California, San Francisco | ||||||
Original Responsible Party | Same as current | ||||||
Current Study Sponsor ICMJE | Sabine Mueller, MD, PhD | ||||||
Original Study Sponsor ICMJE | Same as current | ||||||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | University of California, San Francisco | ||||||
Verification Date | March 2024 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |