Table 1.
Histone deacetylases inhibitors in clinical trial for brain cancer treatment
|
Compound
|
Class
|
Target
|
Conditions
|
Phase of clinical trial
|
Study title
|
| Entinostat | iHDAC (benzamide derivates) | Class I | Brain stem neoplasm | Phase I | Entinostat in Treating Pediatric Patients With Recurrent or Refractory Solid Tumors |
| Pineal region neoplasm | |||||
| Recurrent lymphoma | |||||
| Recurrent malignant solid neoplasm | |||||
| Recurrent primary central nervous system neoplasm | |||||
| Recurrent visual pathway glioma | |||||
| Refractory lymphoma | |||||
| Refractory malignant solid neoplasm | |||||
| Refractory primary central nervous system neoplasm | |||||
| Refractory visual pathway glioma | |||||
| Panobinostat (LBH589) | iHDAC (hydroxymic acids) | Class I, II, IV | Recurrent glioma | Phase I | Panobinostat and Stereotactic Radiation Therapy in Treating Patients With Brain Tumors |
| High-grade meningioma | |||||
| Brain metastasis | |||||
| Panobinostat (LBH589) | iHDAC (hydroxymic acids) | Class I, II, IV | Diffuse intrinsic pontine glioma | Phase I | Phase I Study of Marizomib + Panobinostat for Children With DIPG |
| Pediatric brainstem glioma | |||||
| Pediatric brainstem gliosarcoma recurrent pediatric cancer | |||||
| Pediatric brain tumor | |||||
| Diffuse glioma | |||||
| Panobinostat (LBH589) | iHDAC (hydroxymic acids) | Class I, II, IV | Recurrent malignant gliomas | Phase II | Phase II Trial of LBH589 (Panobinostat) in Adult Patients With Recurrent Malignant Gliomas |
| Valproic Acid | iHDAC (fatty acid derivates) | Class I, II | GBM WHO grade IV | Phase III | International Cooperative Phase III Trial of the HIT-HGG Study Group (HIT-HGG-2013) |
| Diffuse midline glioma histone 3 K27M WHO grade IV | |||||
| Anaplastic astrocytoma WHO grade III | |||||
| Diffuse intrinsic pontine glioma | |||||
| Gliomatosis cerebri | |||||
| Valproic Acid | iHDAC (fatty acid derivates) | Class I, II | Brain metastasis | Phase I | Phase I Study of Temozolomide, Valproic Acid and Radiation Therapy in Patients With Brain Metastases |
| Valproic Acid | iHDAC (fatty acid derivates) | Class I, II | Neuroectodermal tumor | Phase I | Valproate and Etoposide for Patients With Neuronal Tumors and Brain Metastases |
| Brain metastases | |||||
| Advanced cancer | |||||
| Valproic Acid | iHDAC (fatty acid derivates) | Class I, II | Brain tumors | Phase II | Valproic Acid With Temozolomide and Radiation Therapy to Treat Brain Tumors |
| High grade gliomas | |||||
| Vorinostat (SAHA) | iHDAC (hydroxymic acids) | Pan-HDAC | Brain cancer | Phase I/II | Phase I/II Vorinostat, Erlotinib and Temozolomide for Recurrent Glioblastoma Multiforme |
| GBM multiforme | |||||
| Vorinostat (SAHA) | iHDAC (hydroxymic acids) | Pan-HDAC | Adult giant cell GBM | Phase II | Vorinostat and Bortezomib in Treating Patients With Progressive, Recurrent Glioblastoma Multiforme |
| Adult GBM | |||||
| Adult gliosarcoma | |||||
| Recurrent adult brain tumor | |||||
| Vorinostat (SAHA) | iHDAC (hydroxymic acids) | Pan-HDAC | Adult giant cell GBM | Phase II | Vorinostat in Treating Patients With Progressive or Recurrent Glioblastoma Multiforme |
| Adult GBM | |||||
| Adult gliosarcoma | |||||
| Recurrent adult brain tumor | |||||
| Vorinostat (SAHA) | iHDAC (hydroxymic acids) | Pan-HDAC | Recurrent GBM multiforme | Phase II | Ph II SAHA and Bevacizumab for Recurrent Malignant Glioma Patients |
| Malignant glioma | |||||
| Adult brain tumor | |||||
| Vorinostat (SAHA) | iHDAC (hydroxymic acids) | Pan-HDAC | Brain cancer | Phase I | Phase I Vorinostat Concurrent With Stereotactic Radiosurgery (SRS) in Brain Metastases From Non-Small Cell Lung Cancer |
| Neoplasm metastasis | |||||
| Lung cancer | |||||
| Carcinoma, non-small-cell lung | |||||
| Vorinostat (SAHA) | iHDAC (hydroxymic acids) | Pan-HDAC | Brain tumor | Phase I/II | Suberoylanilide Hydroxamic Acid (SAHA), Bevacizumab, Daily Temozolomide for Recurrent Malignant Gliomas |
| GBM | |||||
| Vorinostat (SAHA) | iHDAC (hydroxymic acids) | Pan-HDAC | Brain metastases | Phase I | Study of the Combination of Vorinostat and Radiation Therapy for the Treatment of Patients With Brain Metastases |
| Vorinostat (SAHA) | iHDAC (hydroxymic acids) | Pan-HDAC | Adult GBM | Not applicable | Magnetic Resonance Spectroscopy Imaging in Predicting Response to Vorinostat and Temozolomide in Patients With Recurrent or Progressive Glioblastoma |
| Depression | |||||
| Recurrent adult brain tumor | |||||
| Vorinostat (SAHA) | iHDAC (hydroxymic acids) | Pan-HDAC | Adult anaplastic astrocytoma | Phase I | Vorinostat and Temozolomide in Treating Patients With Malignant Gliomas |
| Adult anaplastic oligodendrogliomaAdult giant cell GBM | |||||
| Adult GBM | |||||
| Adult gliosarcomaAdult mixed glioma | |||||
| Recurrent adult brain neoplasm | |||||
| Vorinostat (SAHA) | iHDAC (hydroxymic acids) | Pan-HDAC | Medulloblastoma | Phase I | Vorinostat Combined With Isotretinoin and Chemotherapy in Treating Younger Patients With Embryonal Tumors of the Central Nervous System |
| Pineoblastoma | |||||
| Supratentorial embryonal tumor | |||||
| Vorinostat (SAHA) | iHDAC (hydroxymic acids) | Pan-HDAC | Brain metastasis | Phase II | Vorinostat and Concurrent Whole Brain Radiotherapy for Brain Metastasis |
| Vorinostat (SAHA) | iHDAC (hydroxymic acids) | Pan-HDAC | Adult anaplastic astrocytoma | Phase I | High-Dose Vorinostat and Fractionated Stereotactic Body Radiation Therapy in Treating Patients With Recurrent Glioma |
| Adult anaplastic oligodendroglioma | |||||
| Adult giant cell GBM | |||||
| Adult GBM | |||||
| Adult gliosarcoma | |||||
| Adult mixed glioma | |||||
| Recurrent adult brain neoplasm | |||||
| Vorinostat (SAHA) | iHDAC (hydroxymic acids) | Pan-HDAC | GBM | Phase I | Pembrolizumab and Vorinostat Combined With Temozolomide for Newly Diagnosed Glioblastoma |
| Brain tumor | |||||
| GBM | |||||
| Vorinostat (SAHA) | iHDAC (hydroxymic acids) | Pan-HDAC | Brain stem glioma | Phase II/III | Vorinostat, Temozolomide, or Bevacizumab in Combination With Radiation Therapy Followed by Bevacizumab and Temozolomide in Young Patients With Newly Diagnosed High-Grade Glioma |
| Cerebral astrocytoma | |||||
| Childhood cerebellar anaplastic astrocytoma | |||||
| Childhood cerebral anaplastic astrocytoma | |||||
| Childhood spinal cord neoplasm | |||||
| Vorinostat (SAHA) | iHDAC (hydroxymic acids) | Pan-HDAC | Adult GBM | Not applicable | Magnetic Resonance Spectroscopy Imaging in Predicting Response to Vorinostat and Temozolomide in Patients With Recurrent or Progressive Glioblastoma |
| Depression | |||||
| Recurrent adult brain tumor | |||||
| Vorinostat (SAHA) | iHDAC (hydroxymic acids) | Pan-HDAC | Adult anaplastic astrocytoma | Phase I | Vorinostat and Temozolomide in Treating Patients With Malignant Gliomas |
| Adult anaplastic oligodendroglioma | |||||
| Adult giant cell GBM | |||||
| Adult GBM | |||||
| Adult gliosarcoma | |||||
| Adult mixed glioma | |||||
| Recurrent adult brain neoplasm | |||||
| Vorinostat (SAHA) | iHDAC (hydroxymic acids) | Pan-HDAC | Medulloblastoma | Phase I | Vorinostat Combined With Isotretinoin and Chemotherapy in Treating Younger Patients With Embryonal Tumors of the Central Nervous System |
| Pineoblastoma | |||||
| Supratentorial embryonal tumor | |||||
| Vorinostat (SAHA) | iHDAC (hydroxymic acids) | Pan-HDAC | Brain metastasis | Phase II | Vorinostat and Concurrent Whole Brain Radiotherapy for Brain Metastasis |
| Vorinostat (SAHA) | iHDAC (hydroxymic acids) | Pan-HDAC | Adult anaplastic astrocytoma | Phase I | High-Dose Vorinostat and Fractionated Stereotactic Body Radiation Therapy in Treating Patients With Recurrent Glioma |
| Adult anaplastic oligodendroglioma | |||||
| Adult giant cell GBM | |||||
| Adult GBM | |||||
| Adult gliosarcoma | |||||
| Adult mixed glioma | |||||
| Recurrent adult brain neoplasm | |||||
| Vorinostat (SAHA) | iHDAC (hydroxymic acids) | Pan-HDAC | GBM | Phase I | Pembrolizumab and Vorinostat Combined With Temozolomide for Newly Diagnosed GBM |
| Brain tumor | |||||
| GBM | |||||
| Vorinostat (SAHA) | iHDAC (hydroxymic acids) | Pan-HDAC | Brain stem glioma | Phase II/III | Vorinostat, Temozolomide, or Bevacizumab in Combination With Radiation Therapy Followed by Bevacizumab and Temozolomide in Young Patients With Newly Diagnosed High-Grade Glioma |
| Cerebral astrocytoma | |||||
| Childhood cerebellar anaplastic astrocytoma | |||||
| Childhood cerebral anaplastic astrocytoma | |||||
| Childhood spinal cord neoplasm | |||||
| Vorinostat (SAHA) | iHDAC (hydroxymic acids) | Pan-HDAC | Childhood atypical teratoid/rhabdoid tumor | Phase I | Vorinostat and Temozolomide in Treating Young Patients With Relapsed or Refractory Primary Brain Tumors or Spinal Cord Tumors |
| Childhood central nervous system choriocarcinoma | |||||
| Childhood central nervous system embryonal tumor and other |
HDAC: Histone deacetylases; iHDAC: HDAC inhibitors; DIPG: Diffuse intrinsic pontine gliomas; WHO: World Health Organization; Ph: Phase; SRS: Stereotactic radiosurgery; GBM: Glioblastoma.