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Immunotherapy (Nivolumab and Ipilimumab) Before and After Surgery for the Treatment of Recurrent or Progressive High Grade Glioma in Children and Young Adults

2020-04-01 04:26:54 | BioPortfolio

Summary

This phase I trial studies the side effects of nivolumab and ipilimumab 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 and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Description

PRIMARY OBJECTIVES:

I. To measure the relative changes in cell cycle-related genetic signature of the tumor microenvironment post administration of neoadjuvant nivolumab and placebo, ipilimumab and placebo, and nivolumab and ipilimumab in children and young adults with recurrent or progressive high grade glioma (HGG) when compared to a cohort of archived non-treated recurrent pediatric HGG samples.

II. To characterize the safety and tolerability of neoadjuvant nivolumab and placebo, neoadjuvant ipilimumab and placebo, and neoadjuvant ipilimumab and nivolumab followed by adjuvant ipilimumab and 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 and placebo, ipilimumab and placebo, or nivolumab and ipilimumab followed by adjuvant nivolumab and ipilimumab.

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 and placebo, ipilimumab and placebo, or nivolumab and ipilimumab followed by adjuvant nivolumab and ipilimumab.

EXPLORATORY OBJECTIVES:

I. To measure relative changes in interferon gamma associated genetic signature within the tumor microenvironment post administration of neoadjuvant nivolumab and placebo, ipilimumab and placebo, or nivolumab and ipilimumab 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 for each treatment arm.

III. To measure TIL density post administration of neoadjuvant nivolumab and placebo compared to neo-adjuvant ipilimumab and placebo, and neoadjuvant nivolumab and ipilimumab 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 and placebo, neoadjuvant ipilimumab and placebo, or neoadjuvant ipilimumab and nivolumab followed by adjuvant ipilimumab and nivolumab.

V. To evaluate the association between advanced magnetic resonance imaging (MRI) parameters (apparent diffusion coefficient (ADC) on diffusion weighted imaging (DWI), relative cerebral blood volume (rCBV) on dynamic susceptibility contrast (DSC) perfusion MRI, pre-contrast T1 shortening on T1-weighed images, and/or magnetization transfer ratio with asymmetric analysis (MTRasym) on pH-weighted amine chemical exchange saturation transfer (CEST)-echo planar imaging (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 and placebo, ipilimumab and placebo, or nivolumab and ipilimumab 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 placebo, neoadjuvant ipilimumab and placebo, or neoadjuvant ipilimumab and nivolumab, and evaluate the differences between the three arms as well as between each group 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 and placebo, neoadjuvant ipilimumab and placebo, or neoadjuvant ipilimumab and nivolumab followed by adjuvant ipilimumab and 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 and placebo, neoadjuvant ipilimumab and placebo, or neoadjuvant ipilimumab and nivolumab followed by adjuvant ipilimumab and nivolumab.

OUTLINE: Patients are randomized to 1 of 3 groups.

GROUP A:

NEOADJUVANT: Patients receive nivolumab intravenously (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.

GROUP B:

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.

GROUP C:

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.

After completion of study treatment, patients are followed up at 30 days and then every 2 months for up to 24 months.

Study Design

Conditions

Glioblastoma

Intervention

Ipilimumab, Nivolumab, Placebo Administration, Quality-of-Life Assessment, Questionnaire Administration

Location

University of California, San Francisco
San Francisco
California
United States
94115

Status

Not yet recruiting

Source

University of California, San Francisco

Results (where available)

View Results

Links

Published on BioPortfolio: 2020-04-01T04:26:54-0400

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