Clinical Trial: Sorafenib Combined With Erlotinib, Tipifarnib, or Temsirolimus in Treating Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase I/II Studies of BAY 43-9006 (Sorafenib) in Combination With OSI-774 (Erlotinib), R115777 (Tipifarnib) or CCI-779 (Temsirolimus) in Patients With Recurrent Glioblastoma Multiforme or

Brief Summary: This phase I/II trial is studying the side effects and best dose of erlotinib, tipifarnib, and temsirolimus when given together with sorafenib and to see how well they work in treating patients with recurrent glioblastoma multiforme or gliosarcoma. Sorafenib, erlotinib, tipifarnib, and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib and tipifarnib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving sorafenib together with erlotinib, tipifarnib, or temsirolimus may kill more tumor cells.

Detailed Summary:

PRIMARY OBJECTIVES:

I Determine the maximum tolerated dose (MTD) of tipifarnib, erlotinib hydrochloride, or temsirolimus in combination with a fixed dose of sorafenib in patients with recurrent glioblastoma mutiforme or gliosarcoma who are not taking enzyme-inducing antiepileptic drugs. (Phase I)

SECONDARY OBJECTIVES:

I. Characterize the safety profile of the doublet combinations of tipifarnib-sorafenib, erlotinib hydrochloride-sorafenib, and temsirolimus-sorafenib in patients with recurrent glioblastoma multiforme or gliosarcoma. (Phase I and II) II. Characterize the pharmacokinetics of these doublet combinations, evaluating single-agent pharmacokinetics of each agent and the combination pharmacokinetics to determine drug-drug interactions. (Phase I and II) III. Determine the efficacy of each of the doublet combinations, in terms of 6-month progression-free survival, in patients with recurrent glioblastoma multiforme or gliosarcoma. (Phase II) IV. Determine the efficacy of each of the doublet combinations, in terms of 12-month survival and objective tumor response, in patients with recurrent glioblastoma multiforme or gliosarcoma. (Phase II)

TERTIARY OBJECTIVES:

I. Perform exploratory correlative laboratory studies by examining tissue markers of signal transduction pathways by immunohistochemical analysis using tissue blocks obtained prior to initiation of protocol therapy, either from the time of diagnosis or subsequent tumor resection. (Phase II) II. Determine the relationship between tumor and blood biomarkers and clinical outcome of patients treated with the combination of targeted agents. (Phase II)

OUTLINE: This is a mu
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Maximally tolerated dose of the each combination agent combined with a fixed dose of BAY 43-9006 determined by dose-limiting toxicities (Phase I) [ Time Frame: 28 days ]
  • Progression-free survival (Phase II) [ Time Frame: 6 months ]
    Distributions will be estimated using Kaplan-Meier method.


Original Primary Outcome:

Current Secondary Outcome: Objective response rate (CR, PR, SD, PD) in patients with measurable disease (Phase II) [ Time Frame: Up to 5 years ]

The proportion of patients in each of the four response categories (CR, PR, SD, PD) will be computed and point estimates and confidence intervals will be provided.


Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: June 8, 2006
Date Started: April 2006
Date Completion:
Last Updated: December 28, 2016
Last Verified: December 2016