Clinical trial NCT00329719
Conditions: Adult Glioblastoma Adult Gliosarcoma Recurrent Adult Brain Neoplasm
Sponsor: National Cancer Institute (NCI)
Start date: 2006-03-24; Completion date: 2013-02-02
Enrollment: 115 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This phase I/II trial studies the side effects and best dose of temsirolimus when given together with sorafenib tosylate and to see how well they work in treating patients with glioblastoma that has come back. Sorafenib tosylate may stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as temsirolimus, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sorafenib tosylate and temsirolimus may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving sorafenib tosylate with temsirolimus may kill more tumor cells.

Detailed description:
Primary Objective -

Phase I (closed to accrual as of 01/11/2008):

To establish a maximum tolerable dose of temsirolimus in combination with sorafenib in patients with recurrent glioblastoma not receiving enzyme-inducing anticonvulsants (EIACs).

Phase II (closed to accrual as of 12/07/2012):

To assess the efficacy of temsirolimus and sorafenib in the treatment of recurrent glioblastoma in non-EIAC patients as measured by progression-free survival status at six months (PFS6).

Secondary Objectives -

Phase I (closed to accrual as of 01/11/2008):

I. To define the safety profile of temsirolimus and sorafenib in non-EIAC patients.

II. To assess the evidence of antitumor activity.

Phase II (closed to accrual as of 12/07/2012):

I. To assess the safety and toxicities of temsirolimus and sorafenib in the above-noted patient populations.

Outline: This is a multicenter, phase I, dose-escalation study followed by a phase II study.

Phase I (Arm A): Patients receive sorafenib orally (PO) twice daily (BID) on days 1-28 and temsirolimus intravenously (IV) over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of temsirolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Phase II: Patients are assigned to 1 of 3 treatment groups.

Group 1 (Arm B): Patients receive sorafenib and temsirolimus as in phase I at the MTD. (patients not undergoing surgery)

Group 2 (Arm C): Patients receive sorafenib PO BID on days 1-8 (15 doses) and temsirolimus IV at the MTD on day 1. Patients undergo surgery on day 8. (patients undergoing surgery) After recovering from surgery, patients receive sorafenib and temsirolimus as in phase I at the MTD.

Group 3 (Arm D): Patient receive sorafenib and temsirolimus as in phase I at the MTD. (patients who have received prior anti-vascular endothelial growth factor \[VEGF\] therapy and are not undergoing surgery)

Biopsy or resected tissue and blood are collected prior to treatment (usually at diagnosis) and analyzed for biomarkers. After completion of study treatment, patients are followed every 6 months for 5 years and then annually thereafter.

Arms: arm 1: Patients receive sorafenib tosylate and temsirolimus as in Phase I. arm 2: Patients receive sorafenib tosylate PO BID on days 1-8 and temsirolimus IV over 30 minutes on day 1. Patients undergo surgery on day 8. After recovering from surgery, patients receive sorafenib tosylate and temsirolimus as in Phase I. arm 3: Patients who have received prior anti-VEGF therapy and are not undergoing surgery receive sorafenib tosylate and temsirolimus as in Phase I.
Interventions: intervention 1: Conventional Surgery intervention 2: Laboratory Biomarker Analysis intervention 3: Sorafenib Tosylate intervention 4: Temsirolimus
Intervention descriptions: intervention 1: Undergo surgery intervention 2: Correlative studies intervention 3: Given PO intervention 4: Given IV

Protocol documents: