Everolimus With and Without Temozolomide in Adult Low Grade Glioma

Low Grade Glioma Clinical Trial

Official title: PI3K/mTOR 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

Clinical Trial Summary

The purpose of this study is to find out what effects, good and/or bad, everolimus (RAD001, also known as Afinitor®) alone or with temozolomide has on the patient and the patient's 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.

Clinical Trial Description

PRIMARY OBJECTIVES:

Arm 1: To assess progression-free survival in patients with previously untreated alpha-thalassemia/mental retardation, X-linked (ATRX) lost and/or 1p/19q intact, phosphatidylinositol 3-kinase (PI3K)/Mechanistic 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 and/or 1p/19q intact, PI3K/mTOR pathway-non-activated LGG treated with everolimus and TMZ.

Arm 3: To assess progression-free survival in patients with previously untreated ATRX intact and/or 1p/19q 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 presence/absence 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 "1p/19q" (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 patient's tumor is 1p/19q 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 patient's tumor is 1p/19q intact and p-PRAS40 negative, the patient will be assigned to Treatment Arm 2. If the patient's tumor is 1p/19q 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. ;

Related Conditions & MeSH terms

• Astrocytoma
• Glioma
• Low Grade Glioma
• Mixed Oligoastrocytomas
• Oligodendroglioma
• Oligodendrogliomas
• World Health Organization (WHO) Grade II Astrocytomas

• NCT number: NCT02023905
• Study type: Interventional
• Source: University of California, San Francisco
• Status: Terminated
• Phase: Phase 2
• Start date: March 19, 2014
• Completion date: September 30, 2021