At a glance
ClinicalIndex Comparison Record- ✓Histologically confirmed glioblastoma, WHO Grade IV (variants allowed; lower-grade gliomas transformed to GBM are eligible if not previously treated)
- ✓Maximal safe resection (biopsy alone is allowed) plus concomitant radiotherapy and temozolomide (minimum 40 Gy radiation)
- ✓Adjuvant temozolomide and Optune start 4–6 weeks after last dose of concomitant chemotherapy or radiotherapy
- ✓Karnofsky performance status ≥70%
- ✕Prior anti-angiogenic agents (e.g., bevacizumab)
- ✕Prior checkpoint inhibitors or T-cell costimulation pathway inhibitors (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4)
- ✕Progressive disease per RANO criteria
- ✕Multifocal gliomas (distinct tumors without overlapping T2/FLAIR signal)
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
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)
In Brief
A Phase 2 clinical trial evaluating Temozolomide (TMZ), Optune System, and 1 other intervention for Glioblastoma and Glioblastoma, WHO Grade IV. Active but no longer recruiting, targeting 40 participants across 1 site.
Detailed 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.
Study Details
Timeline
Interventions
Patients will begin treatment with adjuvant TMZ at least 4 weeks but no more than 6 weeks from last dose of concomitant temozolomide or radiation therapy (the latter of the two). A minimum of 6 and maximum of 12 cycles of adjuvant TMZ will be given depending on tolerability and toxicity.
Patients will undergo 24-months of planned treatment with Optune therapy.
Pembrolizumab will be given intravenously every 3 weeks beginning on Day 1 of Cycle 2 of adjuvant TMZ. Treatment with pembrolizumab every 3 weeks until first disease progression or unacceptable toxicities or 2 years, whichever comes first.