Table 1. Overview of a selection of clinical trials targeting the mTOR-pathway in brain tumor patients.

Entity	Compound	Inclusion	Phase	NCT number	Status
low grade glioma	RAD-001	chemotherapy refractory low grade glioma; children/adults	II	NCT01158651	Active, not recruiting
low grade glioma	RAD-001	recurrent low-grade glioma; adults	II	NCT00823459	Recruiting
low grade glioma	RAD-001	recurrent low-grade glioma; children/adults	II	NCT01734512	Recruiting 1
low-grade glioma	RAD-001	chemotherapy refractory low grade glioma; children/adults	II	NCT00782626	Completed no results available
high-grade glioma	CCI-779+ Perifosine	recurrent/progressive high-greade glioma; adults	I/II	NCT01051557	Active, not recruiting
low-grade glioma	RAD-001 +/- Temozolomide	low-grade glioma; adults	II	NCT02023905	Recruiting
high-grade glioma	RAD-001 +/- Sorafenib	recurrent high-grade glioma; adults	I/II	NCT01434602	Recruiting
high-grade glioma	Rapamycin +Erlotinib	recurrent high-grade glioma; adults	I/II	NCT00509431	Completed no results available
low-grade glioma	RAD-001	recurrent or progressive low grade glioma; adults	II	NCT00831324	Recruiting 2
high-grade glioma	CCI-779+Erlotinib	resurrent high-grade glioms; adults	I/II	NCT00112736	Completed no results available
low-grade glioma	Rapamycin +Tarceva	low-grade glioma with or without NF1-type children/adults	I	NCT00901849	Enrolling by invitation
high-grade glioma	CCI-779	high-grade glioma; adults	I/II	NCT00022724	Completed no results available
Glioblastoma /Gliosarcoms	Rapamycin +Erlotinib	recurrent Glioblastoma / Gliosarcoma; adults	II	NCT00672243	Completed has results
Glioblastoma /Gliosarcoms	RAD-001 +Gleevec +Hydroxyurea	recurrent Glioblastoma / Gliosarcoma; adults	I	NCT00613132	Completed no results available
high-grade glioma	AZD8055	recurrent high grade glioma; adults	I	NCT01316809	Completed no results available
Ependymoma	RAD-001	recurrent or progressive ependymoma; children, adults	II	NCT02155920	Not yet recruiting no results available 3
Glioblastoma	RAD-001	recurrent Glioblastoma; adults	II	NCT00515086	Terminated has results 4
SEGA	RAD-001	SEGAs with Tuberous Sclerosis Complex; children/adults	I/II	NCT00411619	Active, not recruiting
SEGA	RAD-001	SEGAs with Tuberous Sclerosis Complex; children/adults	III	NCT00789828	Active, not recruiting has results
Gliolastoma Prostate Cancer	RAD-001 +Gefitinib	progressive Glioblastoma; adults	I/II	NCT00085566	Completed no results available 5
Glioblastoma	RAD-001 +Temozolomide	newly diagnosed Glioblastoma; adults	I/II	NCT00553150	Active, not recruiting 6
Meningioma	RAD-001 +Bevacizumab	refractory, progressive intracranial meningioma; adults	II	NCT00972335	Active, not recruiting 7
Meningioma /Schwannoma	RAD-001	NF-type 2 / vestibular schwannoma / meningioma; adults	0	NCT01880749	Recruiting
NF-type 2	RAD-001	NF-type 2 patients; children and adults	II	NCT01419639	Active, not recruiting

Some study protocols point on the issue of using tissue biomarkers for additional evaluation of treatment-response as follows:

¹Exploration of associations with pS6 positivity and outcome is planned

²Correlation of phosphorylated PKB/Akt and PTEN expression with response is planned

³Correlation of tumor objective response rate to established immunohistochemical biomarkers of mTOR pathway activation, including pS6, p4EBP1, pPRAS40, pp70S6K and PTEN is planned

⁴Use of Biomarkers: Phosphatase and tensin homolog (PTEN) and Epidermal Growth Factor Receptor (EGFR)

⁵ Comparison of clinical outcome compared to immunohistochemical markers related to the EGFR and PTEN-PI3K-AKT pathways at baseline is planned

⁶ Evaluation of laboratory variables (phospho-Akt, PTEN status, MGMT expression and promoter methylation status)

⁷Correlation of the activity of the treatment regimen with expression of selected intra-tumoral biomarkers

(AZD8055: ATP-competitive mammalian target of rapamycin kinase inhibitor)