Ignite Creation Date:
2025-12-25 @ 3:39 AM
Ignite Modification Date:
2026-02-22 @ 7:50 AM
Study NCT ID:
NCT02530502
Status:
TERMINATED
Last Update Posted:
2023-11-18
First Post:
2015-08-19
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Radiation Therapy With Temozolomide and Pembrolizumab in Treating Patients With Newly Diagnosed Glioblastoma
Sponsor:
Northwestern University
Organization:
Study Overview
Official Title:
Phase I Trial of Radiation Therapy Plus Temozolomide With MK-3475 in Patients With Newly Diagnosed Glioblastoma (GBM)
Status:
TERMINATED
Status Verified Date:
2023-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
The protocol was amendment to be stopped after phase I (phase 2 removed from protocol)
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of phase I trial is to determine the safest, most effective dose of MK-3475 (pembrolizumab), when used with radiotherapy and temozolomide for treating newly diagnosed patients with glioblastoma (GBM). Temozolomide binds to the deoxyribonucleic acid (DNA), changes it, and triggers the death of tumor cells. MK-3475 is an investigational drug, it is not currently approved by the Federal Drug Administration (FDA) for use in treating GBM but it is approved for treating melanoma. MK-3475 works by targets the local tumor immune-protection in solid tumors. It is hoped the addition of MK-3475 to the usual treatment for GBM will improve the current treatment.
Detailed Description:
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of radiation therapy (RT) + temozolomide (TMZ) + MK-3475 (pembrolizumab) followed by MK-3475 + TMZ x 6 cycles (1 cycle is 9 weeks), MK-3475 can continue for an additional 12 months.
SECONDARY OBJECTIVES:
Safety of MK-3475 in GBM.
TERTIARY OBJECTIVES:
I. To determine if there is a correlation of programmed cell death 1 (PD1) or programmed cell death 1 ligand 1 (PDL1) expression and T-cell infiltrate in pathology from first and, if applicable, second surgical specimens with outcome.
II. Assess changes in peripheral T-cell activation and tryptophan metabolites. III. Correlate o-6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) status with outcome.
OUTLINE: This is a phase I, dose-escalation study of pembrolizumab, followed by a phase II study.
RT PORTION: Patients undergo focal RT over 42 days, and receive concurrent temozolomide orally (PO) once daily (QD) on days 1-42 and pembrolizumab IV over 30 minutes on days 1, 22, and 43.
POST-RT: After completion of RT, patients receive temozolomide PO QD on days 1-5 and 29-34 of course 1 and days 1-5 and 29-33 of subsequent courses, and pembrolizumab IV over 30 minutes on days 1, 22, and 43. Treatment repeats every 9 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. After 6 courses, patients deriving benefit may continue to receive pembrolizumab for an additional 12 months.
After completion of study treatment, patients are followed up every 2-4 months.
I. To determine the maximum tolerated dose (MTD) of radiation therapy (RT) + temozolomide (TMZ) + MK-3475 (pembrolizumab) followed by MK-3475 + TMZ x 6 cycles (1 cycle is 9 weeks), MK-3475 can continue for an additional 12 months.
SECONDARY OBJECTIVES:
Safety of MK-3475 in GBM.
TERTIARY OBJECTIVES:
I. To determine if there is a correlation of programmed cell death 1 (PD1) or programmed cell death 1 ligand 1 (PDL1) expression and T-cell infiltrate in pathology from first and, if applicable, second surgical specimens with outcome.
II. Assess changes in peripheral T-cell activation and tryptophan metabolites. III. Correlate o-6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) status with outcome.
OUTLINE: This is a phase I, dose-escalation study of pembrolizumab, followed by a phase II study.
RT PORTION: Patients undergo focal RT over 42 days, and receive concurrent temozolomide orally (PO) once daily (QD) on days 1-42 and pembrolizumab IV over 30 minutes on days 1, 22, and 43.
POST-RT: After completion of RT, patients receive temozolomide PO QD on days 1-5 and 29-34 of course 1 and days 1-5 and 29-33 of subsequent courses, and pembrolizumab IV over 30 minutes on days 1, 22, and 43. Treatment repeats every 9 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. After 6 courses, patients deriving benefit may continue to receive pembrolizumab for an additional 12 months.
After completion of study treatment, patients are followed up every 2-4 months.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2015-00736 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| STU00200883 | None | None | View | |
| NU 15C01 | OTHER | Northwestern University | View | |
| P30CA060553 | NIH | None | https://reporter.nih.gov/quic… | View |