Ignite Creation Date:
2025-12-24 @ 3:15 PM
Ignite Modification Date:
2025-12-27 @ 9:51 PM
Study NCT ID:
NCT03405792
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-10-28
First Post:
2018-01-12
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Study Testing The Safety and Efficacy of Adjuvant Temozolomide Plus TTFields (Optune®) Plus Pembrolizumab in Patients With Newly Diagnosed Glioblastoma (2-THE-TOP)
Sponsor:
University of Florida
Organization:
Study Overview
Official Title:
Phase 2, Single Arm, Historically Controlled Study Testing The Safety and Efficacy of Adjuvant Temozolomide Plus TTFields (Optune®) Plus Pembrolizumab in Patients With Newly Diagnosed Glioblastoma (2-THE-TOP)
Status:
ACTIVE_NOT_RECRUITING
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:
2-THE-TOP
Brief Summary:
Glioblastoma multiforme (GBM) is the most common and deadliest primary malignant neoplasm of the central nervous system in adults. Despite an aggressive multimodality treatment approach including surgery, radiation therapy and chemotherapy, overall survival remains poor. Pembrolizumab has recently been approved in the United States for the treatment of patients with advanced and metastatic non-small cell lung cancer, recurrent or metastatic head and neck squamous cell carcinoma, locally advanced urothelial carcinoma, classical Hodgkin lymphoma, unresectable or metastatic melanoma
This study is being performed to determine whether the triple combination of pembrolizumab when added to TTFields (Optune®) and adjuvant temozolomide increases progression-free survival (PFS) in patients with newly diagnosed GBM as compared to historical control data.
This study is being performed to determine whether the triple combination of pembrolizumab when added to TTFields (Optune®) and adjuvant temozolomide increases progression-free survival (PFS) in patients with newly diagnosed GBM as compared to historical control data.
Detailed Description:
Patients with newly-diagnosed GBM who undergo maximal safe resection (biopsy alone is eligible) followed by standard chemoradiation will be eligible for this trial.
Four weeks after completing chemoradiation, patients will undergo baseline standard of care MRI. Four to six weeks after finishing chemoradiation, patients will start monthly cycles of adjuvant TMZ. A minimum of 6 and maximum of 12 cycles of adjuvant TMZ will be given. Treatment with Optune will start at approximately the same time as the first cycle of adjuvant TMZ and continue until second disease progression or a maximum of 2 years. Within one week after starting Cycle 2 of adjuvant TMZ and Optune therapy, patients will begin open-label treatment with pembrolizumab every 3 weeks until first disease progression or unacceptable toxicities or 2 years, whichever comes first.
At first progression, patients will be allowed to continue with Optune therapy combined with any other therapy, which may include pembrolizumab, per standard of care at the discretion of the treating physician. Surgical resection or biopsy of first recurrent tumor for confirmation of recurrence is allowed within the protocol.
All patients will be seen before Cycle 1 of TMZ, before cycle 2 of TMZ, before starting the second dose of pembrolizumab, and every 3 weeks before each subsequent pembrolizumab dose at an outpatient clinic until they complete all 12 cycles of adjuvant TMZ or discontinue TMZ due to toxicity or first progression.
Medical follow-up will continue for 30 days after treatment termination. After this visit, mortality will be assessed based on telephone interviews with the patients or the patients' caregivers every 3 months.
Four weeks after completing chemoradiation, patients will undergo baseline standard of care MRI. Four to six weeks after finishing chemoradiation, patients will start monthly cycles of adjuvant TMZ. A minimum of 6 and maximum of 12 cycles of adjuvant TMZ will be given. Treatment with Optune will start at approximately the same time as the first cycle of adjuvant TMZ and continue until second disease progression or a maximum of 2 years. Within one week after starting Cycle 2 of adjuvant TMZ and Optune therapy, patients will begin open-label treatment with pembrolizumab every 3 weeks until first disease progression or unacceptable toxicities or 2 years, whichever comes first.
At first progression, patients will be allowed to continue with Optune therapy combined with any other therapy, which may include pembrolizumab, per standard of care at the discretion of the treating physician. Surgical resection or biopsy of first recurrent tumor for confirmation of recurrence is allowed within the protocol.
All patients will be seen before Cycle 1 of TMZ, before cycle 2 of TMZ, before starting the second dose of pembrolizumab, and every 3 weeks before each subsequent pembrolizumab dose at an outpatient clinic until they complete all 12 cycles of adjuvant TMZ or discontinue TMZ due to toxicity or first progression.
Medical follow-up will continue for 30 days after treatment termination. After this visit, mortality will be assessed based on telephone interviews with the patients or the patients' caregivers every 3 months.
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?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| OCR16397 | OTHER | University of Florida | View |