Ignite Creation Date:
2024-05-06 @ 2:51 AM
Last Modification Date:
2024-10-26 @ 11:24 AM
Study NCT ID:
NCT02142803
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-03-01
First Post:
2014-05-16
Brief Title:
TORC12 Inhibitor MLN0128 and Bevacizumab in Treating Patients With Recurrent Glioblastoma or Advanced Solid Tumors
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Phase 1 Study of MLN0128 and Bevacizumab in Patients With Recurrent Glioblastoma and Other Solid Tumors
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-08
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:
None
Brief Summary:
This phase I trial studies the side effects and best dose of raptorrictor-mammalian target of rapamycin mTOR TORC12 inhibitor MLN0128 when given in combination with bevacizumab in treating patients with glioblastoma a type of brain tumor or a solid tumor that has spread and not responded to standard treatment TORC12 inhibitor MLN0128 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth Monoclonal antibodies such as bevacizumab may interfere with the ability of tumor cells to grow and spread Bevacizumab may also stop the progression of tumors by blocking the growth of new blood vessels necessary for tumor growth
Detailed Description:
PRIMARY OBJECTIVES
I To determine the maximum tolerated dose and recommended phase 2 dose MTDRP2D of daily oral MLN0128 TORC12 inhibitor INK128 when administered with bevacizumab in patients with advanced solid tumors including recurrent glioblastoma GBM
II To evaluate the overall safety and tolerability of the combination of MLN0128 and bevacizumab
SECONDARY OBJECTIVES
I To assess the preliminary anti-tumor activity of the combination of MLN0128 and bevacizumab as determined by response rate RR progression-free survival PFS and overall survival OS
II To assess tolerability throughout study therapy with MLN0128 and bevacizumab including beyond the MTD interval with the following measures of cumulative treatment-related toxicities frequency of toxicities leading to missed doses or delays percentage of cycles given or not within 7 days of their scheduled times percentage of actual planned dosage administration percentage of patients that discontinue study drugs due to treatment related toxicity
TERTIARY OBJECTIVES
I To assess cerebrospinal fluid CSF penetration of MLN0128 in combination with bevacizumab in patients with recurrent GBM by evaluating the plasma and CSF concentrations of MLN0128 in the absence and presence of bevacizumab
II To perform archival tumor analysis for markers of dysregulated cell signaling that may predict response to mechanistic target of rapamycin mTOR inhibitor therapy such as epidermal growth factor receptor EGFR expression by immunohistochemistry IHC and amplification by fluorescent in situ hybridization FISH phosphatase and tensin homolog PTEN expression by IHC and deletion by FISH phosphorylated p-protein kinase B AKT p-ribosomal protein S6 kinase S6K p-eukaryotic translation initiation factor 4E binding protein 1 4EBP p-mTOR and p-mitogen-activated protein kinase 1 Erk in patients with recurrent GBM
III To analyze select phosphorylated proteins ERK AKT mTOR 4EBP1 glycogen synthase kinase 3-beta GSK3beta ribosomal protein S6 kinase 70kDa polypeptide 2 p70S6K rS6 from tumor biopsies obtained at baseline and after treatment with MLN0128 from endometrial and ovarian cancer patients enrolled in stage 2
IV To analyze circulating plasma levels of angiogenic growth factors before during and after treatment with MLN0128 and bevacizumab V To perform genetic mutation analysis and proteomic analysis of tissue from biopsies of endometrial and ovarian cancer patients including analysis of Kirsten rat sarcoma viral oncogene homolog KRAS v-raf murine sarcoma viral oncogene homolog B BRAF phosphatidylinositol-45-bisphosphate 3-kinase catalytic subunit alpha PIK3CA v-akt murine thymoma viral oncogene homolog 1 AKT1 and PTEN
OUTLINE This is a dose-escalation study of MLN0128
Patients receive TORC12 inhibitor MLN0128 orally PO once daily QD and bevacizumab intravenously IV over 30-90 minutes on days 1 and 15 Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
After completion of study treatment patients are followed up for 30 days and then annually thereafter
I To determine the maximum tolerated dose and recommended phase 2 dose MTDRP2D of daily oral MLN0128 TORC12 inhibitor INK128 when administered with bevacizumab in patients with advanced solid tumors including recurrent glioblastoma GBM
II To evaluate the overall safety and tolerability of the combination of MLN0128 and bevacizumab
SECONDARY OBJECTIVES
I To assess the preliminary anti-tumor activity of the combination of MLN0128 and bevacizumab as determined by response rate RR progression-free survival PFS and overall survival OS
II To assess tolerability throughout study therapy with MLN0128 and bevacizumab including beyond the MTD interval with the following measures of cumulative treatment-related toxicities frequency of toxicities leading to missed doses or delays percentage of cycles given or not within 7 days of their scheduled times percentage of actual planned dosage administration percentage of patients that discontinue study drugs due to treatment related toxicity
TERTIARY OBJECTIVES
I To assess cerebrospinal fluid CSF penetration of MLN0128 in combination with bevacizumab in patients with recurrent GBM by evaluating the plasma and CSF concentrations of MLN0128 in the absence and presence of bevacizumab
II To perform archival tumor analysis for markers of dysregulated cell signaling that may predict response to mechanistic target of rapamycin mTOR inhibitor therapy such as epidermal growth factor receptor EGFR expression by immunohistochemistry IHC and amplification by fluorescent in situ hybridization FISH phosphatase and tensin homolog PTEN expression by IHC and deletion by FISH phosphorylated p-protein kinase B AKT p-ribosomal protein S6 kinase S6K p-eukaryotic translation initiation factor 4E binding protein 1 4EBP p-mTOR and p-mitogen-activated protein kinase 1 Erk in patients with recurrent GBM
III To analyze select phosphorylated proteins ERK AKT mTOR 4EBP1 glycogen synthase kinase 3-beta GSK3beta ribosomal protein S6 kinase 70kDa polypeptide 2 p70S6K rS6 from tumor biopsies obtained at baseline and after treatment with MLN0128 from endometrial and ovarian cancer patients enrolled in stage 2
IV To analyze circulating plasma levels of angiogenic growth factors before during and after treatment with MLN0128 and bevacizumab V To perform genetic mutation analysis and proteomic analysis of tissue from biopsies of endometrial and ovarian cancer patients including analysis of Kirsten rat sarcoma viral oncogene homolog KRAS v-raf murine sarcoma viral oncogene homolog B BRAF phosphatidylinositol-45-bisphosphate 3-kinase catalytic subunit alpha PIK3CA v-akt murine thymoma viral oncogene homolog 1 AKT1 and PTEN
OUTLINE This is a dose-escalation study of MLN0128
Patients receive TORC12 inhibitor MLN0128 orally PO once daily QD and bevacizumab intravenously IV over 30-90 minutes on days 1 and 15 Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
After completion of study treatment patients are followed up for 30 days and then annually thereafter
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2014-01118 | REGISTRY | None | None |
| 14-079 | None | None | None |
| 9552 | OTHER | None | None |
| 9552 | OTHER | None | None |
| P30CA006516 | NIH | None | None |
| U01CA062490 | NIH | None | None |
| U01CA076576 | NIH | None | None |
| UM1CA186709 | NIH | None | None |
| UM1CA186712 | NIH | CTEP | httpsreporternihgovquickSearchUM1CA186712 |