Immunotherapy Before and After Surgery for Treatment of Recurrent or Progressive High Grade Glioma in Children and Young Adults
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT04323046 |
Recruitment Status :
Recruiting
First Posted : March 26, 2020
Last Update Posted : April 17, 2024
|
Tracking Information | |||||||||
---|---|---|---|---|---|---|---|---|---|
First Submitted Date ICMJE | March 24, 2020 | ||||||||
First Posted Date ICMJE | March 26, 2020 | ||||||||
Last Update Posted Date | April 17, 2024 | ||||||||
Actual Study Start Date ICMJE | October 2, 2020 | ||||||||
Estimated Primary Completion Date | March 1, 2026 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
|
||||||||
Original Primary Outcome Measures ICMJE |
|
||||||||
Change History | |||||||||
Current Secondary Outcome Measures ICMJE |
|
||||||||
Original Secondary Outcome Measures ICMJE |
|
||||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | Immunotherapy Before and After Surgery for Treatment of Recurrent or Progressive High Grade Glioma in Children and Young Adults | ||||||||
Official Title ICMJE | 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) | ||||||||
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. | ||||||||
Detailed Description | PRIMARY OBJECTIVES: I. To measure the relative changes in cell cycle-related genetic signature of the tumor microenvironment post administration of neoadjuvant nivolumab in children and young adults with recurrent or progressive HGG when compared to a cohort of archived non-treated recurrent pediatric HGG samples. II. To characterize the safety and tolerability of neoadjuvant nivolumab followed by adjuvant nivolumab in children and young adults with recurrent or progressive HGG. SECONDARY OBJECTIVES: I. To determine the 6 month and 12 month overall survival (OS) in children and young adults with recurrent or progressive HGG treated with neoadjuvant nivolumab followed by adjuvant nivolumab. II. To determine the 6 month and 12 month progression-free survival (PFS) in children and young adults with recurrent or progressive HGG treated with neoadjuvant nivolumab followed by adjuvant nivolumab. EXPLORATORY OBJECTIVES: I. To measure relative changes in interferon gamma associated genetic signature within the tumor microenvironment post administration of neoadjuvant nivolumab in children and young adults with recurrent or progressive HGG compared to archived non-treated recurrent pediatric HGG samples. II. To explore the correlation of interferon-gamma-associated genetic signature, cell cycle-related genetic signature and infiltrating T lymphocyte (TIL) density and clonality with clinical responses. III. To measure TIL density post administration of neoadjuvant nivolumab in children and young adults with recurrent or progressive HGG. IV. To estimate the objective response rate (ORR) in children and young adults with recurrent or progressive HGG treated with neoadjuvant nivolumab followed by adjuvant nivolumab. V. To evaluate the association between advanced MRI parameters (ADC on DWI, rCBV on dynamic susceptibility contrast (DSC) perfusion MRI, pre-contrast T1 shortening on T1-weighed images, and/or MTRasym on pH-Weighted Amine CEST-EPI) and tumor and peripheral blood immune responses. VI. To measure relative change in peripheral T-cell response and post administration of neo-adjuvant nivolumab in children and young adults with recurrent or progressive HGG. VII. To measure PD-1 and PDL-1 expression by immunohistochemistry for children and young adults with recurrent or progressive HGG post neoadjuvant nivolumab and evaluate the differences between the treatment cohort and archived non-treated recurrent pediatric HGG samples. VIII. To explore the correlation of tumor mutational load with clinical response for children and young adults with recurrent or progressive HGG treated with neoadjuvant nivolumab followed by adjuvant nivolumab. IX. To assess Quality of Life (QOL) and cognitive measures in children and young adults with recurrent or progressive HGG treated with neoadjuvant nivolumab followed by adjuvant nivolumab. X. 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. XI. To assess on therapy toxicity in the context of race, ethnicity and other health related social risks. OUTLINE: Neoadjuvant nivolumab followed by adjuvant nivolumab evaluation. NEOADJUVANT TREATMENT: Participants will receive a single infusion of nivolumab of 3 mg/kg 14± 5 days prior to surgery. When scheduling, please keep in mind that the two pre-surgical plasma samples (day of neoadjuvant dose and day of surgery) should be drawn greater than 10 days apart. Tumor samples will be obtained at time of surgery. The tissue from this surgery (fresh, frozen and FFPE) and the archived tissue (FFPE) from the most recent surgery prior to registration revealing HGG will be processed so as to best achieve the primary, secondary and exploratory objectives. ADJUVANT TREATMENT: Infusion Cycle #1 should begin as soon as participant has recovered from surgery and has been tapered off of steroids. A maximum dexamethasone dose of 0.1 mg/kg/day is allowed, but preferably have been discontinued (inhaled or topical use of steroids is allowed). Maintenance Cycle 1+ Day 1 & 15: Participants will receive nivolumab (3mg/kg) IV every 2 weeks until progression or development of unacceptable toxicities or withdrawal. Blood samples will be obtained as pharmacodynamic markers throughout the study (Day 1 of every other cycle). Dose interruptions and symptomatic management will occur based upon preset adverse event determination. After completion of study treatment, patients are followed up at 30 days and then every 2 months for up to 5 years. |
||||||||
Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Phase 1 | ||||||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
||||||||
Condition ICMJE |
|
||||||||
Intervention ICMJE |
|
||||||||
Study Arms ICMJE | Experimental: Neoadjuvant nivolumab and adjuvant nivolumab
NEOADJUVANT: 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:
|
||||||||
Publications * | Not Provided | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||||||
Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE |
20 | ||||||||
Original Estimated Enrollment ICMJE |
45 | ||||||||
Estimated Study Completion Date ICMJE | March 1, 2029 | ||||||||
Estimated Primary Completion Date | March 1, 2026 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
|
||||||||
Sex/Gender ICMJE |
|
||||||||
Ages ICMJE | 6 Months to 25 Years (Child, Adult) | ||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||
Contacts ICMJE |
|
||||||||
Listed Location Countries ICMJE | Australia, Israel, Switzerland, United States | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT04323046 | ||||||||
Other Study ID Numbers ICMJE | 190815 NCI-2020-01502 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) PNOC 0019 ( Other Identifier: University of California, San Francisco ) |
||||||||
Has Data Monitoring Committee | Yes | ||||||||
U.S. FDA-regulated Product |
|
||||||||
IPD Sharing Statement ICMJE |
|
||||||||
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 | Pacific Pediatric Neuro-Oncology Consortium | ||||||||
Investigators ICMJE |
|
||||||||
PRS Account | University of California, San Francisco | ||||||||
Verification Date | April 2024 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |