Table 1.
Development of combination therapy using epigenetic drugs for the treatment of GBM.
| Clinical Trials Identifier | Clinical Trial Phase | Intervention/Treatment | Condition | Status | Primary Endpoint | Secondary Endpoint | References |
|---|---|---|---|---|---|---|---|
| NCT00268385 | Phase I | Vorinostat + TMZ | GBM | Active | MTD (maximum tolerated dose) of Vorinostat with TMZ | 1. Efficacy in terms of anti-tumor activity based on clinical, radiographic, and biologic assessments 2. Plasma pharmacokinetic parameters of Vorinostat |
[51] |
| NCT00731731 | Phase I/II | Vorinostat + TMZ + RT | Newly diagnosed GBM | Active | 1. MTD of Vorinostat (Phase I) 2. Overall Survival (OS) (Phase II) |
1. Time to tumor progression (Phase II) 2. Incidence of adverse events (Phase II) |
[52] |
| NCT00555399 | Phase I/II | Vorinostat + TMZ + isotretinoin | Recurrent GBM | Completed | MTD | [53] | |
| NCT01738646 | Phase II | Vorinostat + Bevacizumab | Recurrent GBM | Completed | Six-month progression-free survival (PFS) | 1. Radiographic response 2. Median PFS 3. Median OS |
[54] |
| NCT01266031 | Phase I/II | Vorinostat + Bevacizumab | Recurrent GBM | Completed | 1. PFS at 6 Months 2. MTD of Oral Vorinostat used with Bevacizumab |
1. Time to Tumor Progression 2. OS 3. Effects of Bevacizumab with and without Vorinostat upon biomarkers 4. Mean symptom interference at the time of clinical evaluation 5. Radiological response |
[55] |
| NCT00762255 | Phase I | Vorinostat + Bevacizumab + irinotecan | Recurrent GBM | Completed | MTD | 1. PFS at 6 months 2. Number of participants with adverse events |
[56] |
| NCT00939991 | Phase I/II | Vorinostat + TMZ + Bevacizumab | Recurrent GBM | Completed | 1. Determination of MTD (Phase I) 2. 6-month PFS (Phase II) |
1. Radiographic response (Phase II) 2. PFS (Phase II) 3. OS (Phase II) 4. Number of patients with Grade 2 or greater, treatment-related toxicities (Phase II) |
[57] |
| NCT01236560 | Phase II/III | Vorinostat + TMZ + Bevacizumab | Young newly diagnosed GBM | Active | 1. MTD of Vorinostat 2. Event-free survival |
1. OS 2. Cumulative incidence of disease progression in each treatment arm |
[58] |
| NCT00641706 | Phase II | Vorinostat + Bortezomib | Recurrent GBM | Completed | PFS at 6 Months | 1. OS 2. Time to tumor progression 3. Proportion of confirmed tumor response |
[59] |
| NCT01110876 | Phase I/II | Vorinostat + TMZ + Enlotinib | Recurrent GBM | Terminated | MTD of Vorinostat in combination with escalating doses of erlotinib and TMZ | PFS | [60] |
| NCT03426891 | Phase I | Vorinostat + Pembrolizumab + TMZ + RT | GBM | Active | MTD | OS | [61] |
| NCT02137759 | Phase II | Belinostat + TMZ + RT | Newly diagnosed GBM | Active | 1. PFS 2. MTD |
1. PFS 2. OS 3. IDS-SR score change |
[62] |
| NCT00302159 | Phase II | Valproic acid + TMZ + RT | GBM | Completed | 1. Median PFS 2. Percentage of participants with PFS at 6, 12, and 24 months 3. Number of participants with best response 4. Median OS 5. Percentage of participants with OS at 6, 12, and 24 months |
Number of participants with adverse events | [63] |
| NCT00879437 | Phase II | Valproic acid + Bevacizumab + RT | GBM | Terminated | One-year event-free survival | 1. Median EFS 2. Median OS 3. Partial response in diffuse intrinsic pontine Glioma 4. Partial response in high-grade Gliomas 5. Complete response in high-grade Gliomas |
[64] |
| NCT02648633 | Phase I | Valproic acid + Nivolumab + RT | GBM | Completed | 1. Feasibility based on number of subjects who complete 4 doses of nivolumab 2. Incidence of adverse events |
1. Clinical response rate 2. Incidence of pseudoprogressions |
[65] |
| NCT01817751 | Phase II | Valproic acid + sorafenib tosylate + sildenafil citrate | GBM | Active | PFS | 1. Overall best response rate 2. OS 3. Incidence of adverse events |
[66] |
| NCT03243461 | Phase III | Valproic acid + TMZ | GBM | Active | Comparison of effects of Valproine acid with respect to historical control group | [67] | |
| NCT00859222 | Phase I/II | Bevacizumab + Panobinostat | Recurrent GBM | Completed | 1. LBH589 MTD (Phase I) 2. Dose limiting toxicity (Phase I) 3. PFS at 6 months (Phase II) |
1. Best radiographic response 2. PFS (Phase II) 3. OS (Phase II) |
[68] |
| NCT03684811 | Phase I/II | Azacitidine + FT-2102 | GBM | Active | 1. Number of participants with dose limiting toxicity (Phase 1) 2. Doses recommended for future studies (Phase 1) 3. Objective response rate of FT-2102 single agent or in combination with Azacitidine (Phase 2) |
Phase 1 and 2: 1. OS 2. Time to response (TTR) 3. Time to tumor progression 4. Duration of response (DOR) 5. PFS 6. Drug level within CSF |
[69] |
| NCT04614909 | Early Phase I | Olaparib + TMZ + RT | Newly diagnosed GBM | Active | Systemic plasma PK profile parameters | 1. PFS participants with demonstrated PK effects 2. OS 3. Drug-related toxicity 4. Adverse events 5. Treatment-emergent adverse events 6. Deaths |
[70] |
| NCT02152982 | Phase II/III | Veliparib + TMZ | Newly diagnosed GBM | Active | OS | 1. Interaction with Optune device 2. PFS 3. Objective tumor response 4. Overall adverse event rates for grade 3 or higher adverse events 5. Change in quality of life (QOL) |
[71] |
| NCT01026493 | Phase I/II | Veliparib + TMZ | Recurrent GBM | Completed | 1. MTD (Phase I) 2. 6-month PFS rate for patients with measurable disease after surgery (Phase II) |
Phase II: 1. Objective response rate for patients with measurable disease after surgery 2. OS |
[72] |
| NCT03581292 | Phase II | Veliparib + TMZ + RT | GBM | Active | Event-free Survival | 1. Objective response 2. OS |
[73] |