University of Alabama at Birmingham, Children's of Alabama 35233 Birmingham United StatesRekrutierend» Google-Maps Ansprechpartner: Girish Dhall, MD Phone: 205-638-9285 E-Mail: gdhall@peds.uab.edu
Katie Metrock, MD E-Mail: kmetrock@peds.uab.edu» Ansprechpartner anzeigenChildren's Hospital of Los Angeles 90027 Los Angeles United StatesRekrutierend» Google-Maps Ansprechpartner: Tom Davidson, MD Phone: 323-361-8147 E-Mail: tdavidson@chla.usc.edu» Ansprechpartner anzeigenRady Children's Hospital 92123 San Diego United StatesRekrutierend» Google-Maps Ansprechpartner: Megan Paul, MD E-Mail: mrpaul@rchsd.org» Ansprechpartner anzeigen
University of California, San Francisco 94115 San Francisco United StatesRekrutierend» Google-Maps Ansprechpartner: Sabine Mueller, MD, Phd E-Mail: Sabine.Mueller@ucsf.edu» Ansprechpartner anzeigenChildren's National Hospital 20310 Washington United StatesRekrutierend» Google-Maps Ansprechpartner: Lindsay Kilburn, MD Phone: 202-476-5973 E-Mail: lkilburn@cnmc.org» Ansprechpartner anzeigenUniversity of Florida 32611 Gainesville United StatesRekrutierend» Google-Maps Ansprechpartner: Elias Sayour, MD, PhD Phone: 352-294-8347 E-Mail: elias.sayour@neurosurgery.ufl.edu» Ansprechpartner anzeigenRiley Children's Hospital 46202 Indianapolis United StatesRekrutierend» Google-Maps Ansprechpartner: Scott Coven, DO, MPH Phone: 317-944-8784 E-Mail: scoven@iu.edu» Ansprechpartner anzeigenJohns Hopkins University 21287 Baltimore United StatesRekrutierend» Google-Maps Ansprechpartner: Kenneth Cohen, MD, MBA Phone: 410-614-5055 E-Mail: kcohen@jhmi.edu
Eric Raabe, MD E-Mail: eraabe2@jhmi.edu» Ansprechpartner anzeigenDana Farber Cancer Institute 02215 Boston United StatesRekrutierend» Google-Maps Ansprechpartner: Susan Chi, MD Phone: 617-632-2291 E-Mail: susan_chi@dfci.harvard.edu» Ansprechpartner anzeigenWashington University St. Louis 63110 Saint Louis United StatesRekrutierend» Google-Maps Ansprechpartner: Mohamed Abdelbaki, MD Phone: 314-286-2790 E-Mail: mohameda@wustl.edu» Ansprechpartner anzeigenHackensack Meridian Children's Health at Joseph M. Sanzari Children's Hospital 07601 Hackensack United StatesRekrutierend» Google-Maps Ansprechpartner: Derek Hanson, MD Phone: 551-996-5437 E-Mail: derek.hanson@hmhn.org» Ansprechpartner anzeigenDoernbecher Children's Hospital Oregon Health & Science University 97239 Portland United StatesRekrutierend» Google-Maps Ansprechpartner: Linda Stork, MD Phone: 503-494-1543 E-Mail: storkl@ohsu.edu
Matthew Miller, MD E-Mail: milmatth@ohsu.edu» Ansprechpartner anzeigenUniversity of Utah 84113 Salt Lake City United StatesRekrutierend» Google-Maps Ansprechpartner: Nicholas Whipple, MD E-Mail: nicholas.whipple@hsc.utah.edu
1. Percentage change in cell cycle-related genetic signature (Time Frame - From screening to surgery visit (neoadjuvant treatment groups); at time of recurrent high grade glioma (HGG) tissue collection (for archived non-treated samples)): Will assess the percentage change in cell cycle-related genetic signature post administration of neoadjuvant treatments when compared to archived recurrent pediatric HGG group. The number of participants with high cell cycle gene signature (positive median gene set variation analysis (GSVA) score) will be tabulated. Variables involved in the primary analyses will be examined graphically and summarized by descriptive statistics.
2. Proportion of participants with treatment-related adverse events (Time Frame - Up to 2 years): Adverse events will be monitored throughout the trial and graded in severity according to the guidelines outlined in the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 from initiation of study treatment until 2 years after treatment discontinuation or until study treatment related adverse events resolve or return to baseline, Adverse experiences (specific terms as well as system organ class terms) and predefined limits of change in laboratory, and vital sign parameters that are not pre-specified as events of interest will be summarized with descriptive statistics (counts, percentage, mean, standard deviation, etc.).
Secondary outcome:
1. Overall survival (Time Frame - Up to 12 months): Survival will be assessed at 6 months and 12 months from the time of enrollment until the time of death. Kaplan-Meier survival analyses will be performed. Medians together with 2-sided 95% confidence intervals will be computed using a log-log transformation.
2. Progression-free survival (PFS) (Time Frame - Up to 12 months): PFS is defined as the time of enrollment until the time of progressive disease or death. Kaplan-Meier survival analyses will be performed. Medians together with 2-sided 95% confidence intervals will be computed using a log-log transformation.
Experimental: Group A (neoadjuvant nivolumab and placebo) NEOADJUVANT: Patients receive nivolumab IV over 30 minutes and placebo IV over 30 minutes 14 days before undergoing standard of care surgical resection.
ADJUVANT COMBINATION INFUSION: After recovery from surgery (no more than 35 days afterwards), patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
ADJUVANT MAINTENANCE: After completion of combination infusion, patients receive nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Experimental: Group B (neoadjuvant nivolumab and ipilimumab) NEOADJUVANT: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes 14 days before undergoing standard of care surgical resection.
ADJUVANT COMBINATION INFUSION: After recovery from surgery (no more than 35 days afterwards), patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
ADJUVANT MAINTENANCE: After completion of combination infusion, patients receive nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Experimental: Group C (neoadjuvant placebo and ipilimumab) NEOADJUVANT: Patients receive placebo IV over 30 minutes and ipilimumab IV over 30 minutes 14 days before undergoing standard of care surgical resection.
ADJUVANT COMBINATION INFUSION: After recovery from surgery (no more than 35 days afterwards), patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
ADJUVANT MAINTENANCE: After completion of combination infusion, patients receive nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.