Immunotherapy Before and After Surgery for Treatment of Recurrent or Progressive High Grade Glioma in Children and Young Adults
A Single Arm, Pilot of Neoadjuvant Checkpoint Inhibition Followed by Adjuvant Checkpoint Inhibition in Children and Young Adults With Recurrent or Progressive High Grade Glioma (HGG)
3 other identifiers
interventional
20
2 countries
20
Brief Summary
This phase I trial studies the side effects of nivolumab before and after surgery in treating children and young adults with high grade glioma that has come back (recurrent) or is increasing in scope or severity (progressive). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Oct 2020
Longer than P75 for phase_1
20 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 24, 2020
CompletedFirst Posted
Study publicly available on registry
March 26, 2020
CompletedStudy Start
First participant enrolled
October 2, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2029
ExpectedMay 4, 2025
May 1, 2025
5.4 years
March 24, 2020
May 2, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
Percentage change in cell cycle-related genetic signature
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.
From screening to surgery visit (neoadjuvant treatment groups); at time of recurrent high grade glioma (HGG) tissue collection (for archived non-treated samples)
Proportion of participants with treatment-related adverse events
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.).
Up to 2 years
Secondary Outcomes (2)
Overall survival
Up to 12 months
Progression-free survival (PFS)
Up to 12 months
Study Arms (1)
Neoadjuvant nivolumab and adjuvant nivolumab
EXPERIMENTALNEOADJUVANT: Patients receive nivolumab IV over 30 minutes 14 days before undergoing standard of care surgical resection. ADJUVANT MAINTENANCE: After completion of neoadjuvant 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.
Interventions
Given IV
Ancillary studies, given in person or online
Ancillary studies, given in person or online
Eligibility Criteria
You may qualify if:
- Participants with recurrent or progressive high-grade gliomas (HGG) (World Health Organization (WHO) grade III or grade IV) who are candidates for surgical tumor debulking will be enrolled in this trial
- All assessments are to occur within 14 days of registration except where otherwise noted. The participant and their legal parent/guardian must be thoroughly informed about all aspects of the study, including the study visit schedule and required evaluations and all regulatory requirements for informed consent. The written informed consent must be obtained from the participant and legal parent/guardian prior to enrollment
- Have a history of previously treated histologically confirmed World Health Organization grade III or IV HGG. Previous first line therapy with radiation and/or chemotherapy
- Have evidence of recurrence or progression of disease by MRI scan
- Participants must be adequate medical candidates for surgical resection. The intent of surgical resection is to allow both cytoreduction and tumor debulking as part of standard of care, and also collect a minimum of 100 mg of tumor tissue for the study tissue endpoints
- A primary goal of surgery must be cytoreduction, and not solely on diagnostic biopsy
- Age: Participants must be \> 6 months and \< 25 years of age at time of enrollment
- Karnofsky \>= 50 for participants \> 16 years of age and Lansky \>= 50 for participants =\< 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
- Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment (on stable or tapering dosing of steroids). A baseline detailed neurological exam should clearly document the neurologic status of the patient at the time of enrollment on the study.
- Prior Therapy: Participants must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the defined eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
- Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. At least 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
- An interval of at least 12 weeks from the completion of radiation therapy to registration unless there is unequivocal histologic confirmation of tumor progression
- Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events (AEs) are known to occur. The duration of this interval must be discussed with the study chair.
- Had their last dose of biologic (anti-neoplastic agent) ≥7 days prior to study registration, or beyond the time during which AEs are known to occur.
- Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): At least 7 days after the last dose of agent
- +22 more criteria
You may not qualify if:
- Current or planned participation in a study of an investigational agent or using an investigational device.
- Has a diagnosis of immunodeficiency.
- Has tumor primarily localized to the brainstem or spinal cord.
- Has presence of diffuse leptomeningeal disease or or disseminated/multi-focal disease, or extracranial disease.
- Has received systemic immunosuppressive treatments (such as methotrexate, chloroquine, azathioprine, etc.), aside from anti-neoplastic chemotherapy or systemic corticosteroids within six months of registration.
- Participants with a concurrent condition requiring systemic treatment with either corticosteroids (\> 0.25 mg/kg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses \> 0.25 mg/kg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
- Unable to taper steroids due to ongoing mass effect; a maximum dexamethasone dose of 0.1 mg/kg/day is allowed (4mg maximum), but preferably have been discontinued (inhaled or topical use of steroids is allowed).
- Has a known history of active TB (Bacillus tuberculosis).
- Has a known additional malignancy that is progressing or requires active treatment within 3 years of registration. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has known history of, or any evidence of active non-infectious pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a known hypersensitivity to any of the study therapy products.
- Has a known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
- NOTE: Testing for HIV must be performed at sites where mandated locally
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Sabine Mueller, MD, PhDlead
- Pediatric Neuro-Oncology Consortiumcollaborator
Study Sites (20)
University of Alabama at Birmingham, Children's of Alabama
Birmingham, Alabama, 35233, United States
Children's Hospital of Los Angeles
Los Angeles, California, 90027, United States
Rady Children's Hospital
San Diego, California, 92123, United States
University of California, San Francisco
San Francisco, California, 94115, United States
Children's National Hospital
Washington D.C., District of Columbia, 20310, United States
University of Florida
Gainesville, Florida, 32611, United States
Riley Children's Hospital
Indianapolis, Indiana, 46202, United States
Johns Hopkins University
Baltimore, Maryland, 21287, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Washington University St. Louis
St Louis, Missouri, 63110, United States
Hackensack Meridian Children's Health at Joseph M. Sanzari Children's Hospital
Hackensack, New Jersey, 07601, United States
Duke Children's Hospital & Health Center
Durham, North Carolina, 27705, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
University of Utah
Salt Lake City, Utah, 84113, United States
Sydney Children's Hospital
Sydney, New South Wales, 1291, Australia
The Children's Hospital at Westmead
Westmead, New South Wales, 2152, Australia
Queensland Children's Hospital
South Brisbane, Queensland, 4101, Australia
Women's and Children's Hospital
North Adelaide, South Australia, 5006, Australia
Royal Children's Hospital
Parkville, Victoria, 3052, Australia
Perth Children's' Hospital
Perth, Western Australia, 6009, Australia
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Tom Davidson (tdavidson@chla.usc.edu), MD
Children's Hospital Los Angeles
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
March 24, 2020
First Posted
March 26, 2020
Study Start
October 2, 2020
Primary Completion
March 1, 2026
Study Completion (Estimated)
March 1, 2029
Last Updated
May 4, 2025
Record last verified: 2025-05
Data Sharing
- IPD Sharing
- Will not share