Ignite Creation Date:
2025-12-24 @ 2:25 PM
Ignite Modification Date:
2026-01-02 @ 4:31 AM
Study NCT ID:
NCT03557359
Status:
COMPLETED
Last Update Posted:
2025-11-03
First Post:
2018-05-17
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Nivolumab for Recurrent or Progressive IDH Mutant Gliomas
Sponsor:
Fabio Iwamoto, MD
Organization:
Study Overview
Official Title:
A Phase II, Open Label, Single Arm Study of Nivolumab for Recurrent or Progressive IDH Mutant Gliomas With Prior Exposure to Alkylating Agents
Status:
COMPLETED
Status Verified Date:
2025-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The objective of this study is to determine response rates (partial and complete responses) to nivolumab of recurrent or progressive IDH mutant (grades 2, 3 or 4) gliomas with prior exposure to alkylating agents.
Detailed Description:
Gliomas are the most common malignant primary brain tumor in adults. Their clinical presentation is heterogeneous and prognosis is dependent on both the grade of the tumor and the molecular subtype. Somatic mutations in Isocitrate dehydrogenase 1 (IDH1) or, less commonly, Isocitrate dehydrogenase 2 (IDH2) genes have emerged as an important prognostic factor in gliomas and are associated with longer survival.
Regardless of initial grade, recurrence and transformation into higher grade tumors is almost universal. There is high unmet medical need in treating recurrent gliomas as there is currently no established standard of care therapy. Recent trials of IDH inhibitors in IDH mutant gliomas and programmed cell death protein 1 (PD-1) and PD-L1 inhibitors in recurrent gliomas have been disappointing. Multiple studies in other cancers have demonstrated that hypermutated tumors are associated with response to immunotherapeutic agents, including anti-CTLA4 agents in melanoma, anti-PD1 therapy in bladder cancer, and anti-programmed-cell-death protein 1 (anti-PD1) therapy in lung, and colorectal cancer.
There is evidence to suggest that gliomas with somatic IDH mutations are more prone to develop hypermutation after exposure to alkylating agents than IDH wildtype tumors, providing strong scientific rationale for establishing nivolumab as a treatment option in this subgroup of patients.
Regardless of initial grade, recurrence and transformation into higher grade tumors is almost universal. There is high unmet medical need in treating recurrent gliomas as there is currently no established standard of care therapy. Recent trials of IDH inhibitors in IDH mutant gliomas and programmed cell death protein 1 (PD-1) and PD-L1 inhibitors in recurrent gliomas have been disappointing. Multiple studies in other cancers have demonstrated that hypermutated tumors are associated with response to immunotherapeutic agents, including anti-CTLA4 agents in melanoma, anti-PD1 therapy in bladder cancer, and anti-programmed-cell-death protein 1 (anti-PD1) therapy in lung, and colorectal cancer.
There is evidence to suggest that gliomas with somatic IDH mutations are more prone to develop hypermutation after exposure to alkylating agents than IDH wildtype tumors, providing strong scientific rationale for establishing nivolumab as a treatment option in this subgroup of patients.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: