Clinical Trial 18647

Cancer Type: Neurologic Oncology
Interventions:BMS-936558 (Nivolumab); Nivolumab; Placebo; Temodal (Temozolomide); Temozolomide

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Solmaz Sahebjam

Overview

Study Title

A Randomized Phase 2 Single Blind Study of Temozolomide plus Radiation Therapy combined with Nivolumab or Placebo in Newly Diagnosed Adult Subjects with MGMT-Methylated (tumor O6-methylguanine DNA methyltransferase) Glioblastoma

Summary

The purpose of this study is to test the effectiveness (how well the drug works), safety, and tolerability of an investigational drug called nivolumab (also known as BMS-936558). Nivolumab is an antibody (a type of human protein) that is being tested to see if it will allow the body's immune system to work against tumor cells. The effectiveness of nivolumab in glioblastoma (GBM or brain cancer) will be determined by comparing the survival of participants who receive the investigational drug nivolumab combined with temozolomide and radiotherapy compared with those who receive temozolomide with radiotherapy (a recommended therapy for newly diagnosed GBM) and placebo. Another purpose of this study is to test how well investigators can detect the expression of a biomarker known as PD-L1. This type test is known as an in vitro diagnostic, or IVD. The IVD in this study is an investigational device.

Objective

Objectives: Primary Objective: To compare overall survival (OS) of subjects with newly-diagnosed MGMT-methylated, partially methylated, or indeterminate GBM treated with RT plus TMZ combined with nivolumab or placebo. Secondary Objective: To compare progression-free survival (PFS) of subjects with newly-diagnosed MGMT-methylated, partially methylated, or indeterminate GBM treated with RT plus TMZ with nivolumab or placebo. Exploratory Objectives: To evaluate the safety and tolerability of RT+TMZ combined with nivolumab or placebo. To assess immune-related tumor effects during nivolumab treatment using histopathology and advanced imaging in conjunction with other studies of nivolumab in GBM. To assess neurocognitive function of RT+TMZ with nivolumab or placebo using the Neurologic Assessment in Neuro-Oncology (NANO) Scale and the Cogstate tool. To evaluate health-related quality of life using the EQ-5D3L and the European Organization for Research and Treatment of Care General Cancer Module (QLQ-C30) and brain cancer module (QLQ-BN20). To investigate the association between biomarkers in the peripheral blood and tumor tissue, such as PD-L1 expression, with safety and efficacy in subjects treated with nivolumab. To evaluate the pharmacodynamic activity of nivolumab in the peripheral blood and tumor tissue as measured by flow cytometry, immunohistochemistry, soluble factor analysis, and gene expression (microarray technology, quantitative RT-PCR). To characterize the PK of nivolumab and explore exposure-response relationships. To characterize the immunogenicity of nivolumab in this setting. Where statistically appropriate, to combine data from this study with other studies of nivolumab in GBM.

Inclusion Criteria

  • Males and Females, age ≥ 18 years old
  • Newly diagnosed brain cancer or tumor called glioblastoma or GBM
  • Karnofsky performance status of ≥ 70 (able to take care of self)
  • Substantial recovery from surgery resection
  • Tumor test result shows tumor O-6-methylguanine DNA methyltransferase (MGMT) methylated or indeterminate tumor subtype
  • Other protocol defined inclusion criteria could apply

  • Exclusion Criteria

  • Biopsy-only of GBM with less than 20% of tumor removed
  • Prior treatment for GBM (other than surgical resection)
  • Any known tumor outside of the brain
  • Recurrent or secondary GBM
  • Active known or suspected autoimmune disease
  • Other protocol defined exclusion criteria could apply