Ignite Creation Date:
2024-05-06 @ 2:21 AM
Last Modification Date:
2024-10-26 @ 11:17 AM
Study NCT ID:
NCT02023905
Status:
TERMINATED
Last Update Posted:
2022-12-29
First Post:
2013-12-24
Brief Title:
Everolimus With and Without Temozolomide in Adult Low Grade Glioma
Sponsor:
University of California San Francisco
Organization:
University of California San Francisco
Study Overview
Official Title:
PI3KmTOR Pathway Activation Selected Phase II Study of Everolimus RAD001 With and Without Temozolomide in the Treatment of Adult Patients With Supratentorial Low-Grade Glioma
Status:
TERMINATED
Status Verified Date:
2022-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Sponsor decision
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to find out what effects good andor bad everolimus RAD001 also known as Afinitor alone or with temozolomide has on the patient and the patients low-grade glioma Everolimus is being investigated as an anticancer agent based on its potential to prevent tumor cells from growing and multiplying Specifically there is a protein called mTOR that we think helps many tumors to grow and everolimus blocks the effect of mTOR Temozolomide is also an anticancer agent that prevents tumor cells from growing and multiplying
Detailed Description:
PRIMARY OBJECTIVES
Arm 1 To assess progression-free survival in patients with previously untreated alpha-thalassemiamental retardation X-linked ATRX lost andor 1p19q intact phosphatidylinositol 3-kinase PI3KMechanistic target of rapamycin mTOR pathway-activated low grade-glioma LGG treated with everolimus
Arm 2 To assess progression-free survival in patients with previously untreated ATRX lost andor 1p19q intact PI3KmTOR pathway-non-activated LGG treated with everolimus and TMZ
Arm 3 To assess progression-free survival in patients with previously untreated ATRX intact andor 1p19q co-deleted LGG treated with everolimus
SECONDARY OBJECTIVES
1 To assess overall and progression-free survival distributions Arms 1 2 3
2 To assess the objective response rate to treatment Arms 1 2 3
3 To further delineate the safety profile of the combination of everolimus and TMZ Arm 2
4 To assess whether treatment Arms 1 2 3 provides clinical benefit by reducing seizure frequency
EXPLORATORY OBJECTIVES
1 Pending adequate funding to assess the ability of metabolic and physiologic imaging parameters such as magnetic resonance MR spectroscopy perfusion-weighted imaging and diffusion-weighted imaging to predict clinically relevant endpoints such as time to progression and survival
2 To assess for an association between the presenceabsence of clonal or subclonal genetic mutations in the PI3K pathway and Median progression-free survival PFS Objective Response Rate ORR phosphatase and tensin homolog PTEN gene methylation and the immunohistochemical measurements of the PI3K pathway activation in patients treated with everolimus or TMZ and everolimus
3 To longitudinally assess quality of life QoL in low-grade glioma patients over the course of treatment with everolimus Arms 1 3
OUTLINE
Patients will be assigned to one of 3 treatment arms based on two characteristics of their tumor called 1p19q this is a test of the tumor chromosomes and p-PRAS40 this is a test of a pathway in the tumor called mTOR If the patients tumor is 1p19q intact and the phosphorylation of proline-rich Ak strain transforming AKT substrate of 40 kDa encoded by the gene AKT1S1 p-PRAS40 positive the patient will be assigned to Treatment Arm 1 If the patients tumor is 1p19q intact and p-PRAS40 negative the patient will be assigned to Treatment Arm 2 If the patients tumor is 1p19q co-deleted regardless of the p-PRAS40 result the patient will be assigned to Treatment Arm 3
All patients will be observed for safety for 30 days following the last dose of everolimus After completion of study treatment patients whose tumors have not progressed will be followed with interval MRIs for an additional 2 years and thereafter as per the discretion of the managing physician Patients off protocol therapy will continue to be followed for survival only
Arm 1 To assess progression-free survival in patients with previously untreated alpha-thalassemiamental retardation X-linked ATRX lost andor 1p19q intact phosphatidylinositol 3-kinase PI3KMechanistic target of rapamycin mTOR pathway-activated low grade-glioma LGG treated with everolimus
Arm 2 To assess progression-free survival in patients with previously untreated ATRX lost andor 1p19q intact PI3KmTOR pathway-non-activated LGG treated with everolimus and TMZ
Arm 3 To assess progression-free survival in patients with previously untreated ATRX intact andor 1p19q co-deleted LGG treated with everolimus
SECONDARY OBJECTIVES
1 To assess overall and progression-free survival distributions Arms 1 2 3
2 To assess the objective response rate to treatment Arms 1 2 3
3 To further delineate the safety profile of the combination of everolimus and TMZ Arm 2
4 To assess whether treatment Arms 1 2 3 provides clinical benefit by reducing seizure frequency
EXPLORATORY OBJECTIVES
1 Pending adequate funding to assess the ability of metabolic and physiologic imaging parameters such as magnetic resonance MR spectroscopy perfusion-weighted imaging and diffusion-weighted imaging to predict clinically relevant endpoints such as time to progression and survival
2 To assess for an association between the presenceabsence of clonal or subclonal genetic mutations in the PI3K pathway and Median progression-free survival PFS Objective Response Rate ORR phosphatase and tensin homolog PTEN gene methylation and the immunohistochemical measurements of the PI3K pathway activation in patients treated with everolimus or TMZ and everolimus
3 To longitudinally assess quality of life QoL in low-grade glioma patients over the course of treatment with everolimus Arms 1 3
OUTLINE
Patients will be assigned to one of 3 treatment arms based on two characteristics of their tumor called 1p19q this is a test of the tumor chromosomes and p-PRAS40 this is a test of a pathway in the tumor called mTOR If the patients tumor is 1p19q intact and the phosphorylation of proline-rich Ak strain transforming AKT substrate of 40 kDa encoded by the gene AKT1S1 p-PRAS40 positive the patient will be assigned to Treatment Arm 1 If the patients tumor is 1p19q intact and p-PRAS40 negative the patient will be assigned to Treatment Arm 2 If the patients tumor is 1p19q co-deleted regardless of the p-PRAS40 result the patient will be assigned to Treatment Arm 3
All patients will be observed for safety for 30 days following the last dose of everolimus After completion of study treatment patients whose tumors have not progressed will be followed with interval MRIs for an additional 2 years and thereafter as per the discretion of the managing physician Patients off protocol therapy will continue to be followed for survival only
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2014-00749 | REGISTRY | NCI Clinical Trials Reporting Program CTRP | None |
| 131012 | OTHER | None | None |