NCT00255658

Sorafenib and Temsirolimus in Treating Patients With Unresectable or Metastatic Solid Tumors

Phase I, Pharmacokinetic and Pharmacodynamic Study of BAY 43-9006 (Sorafenib) in Combination With CCI-779 (Temsirolimus) in Advanced Solid Malignancies

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial is studying the side effects and best dose of temsirolimus when given together with sorafenib in treating patients with unresectable or metastatic solid tumors. Sorafenib and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving sorafenib together with temsirolimus may kill more tumor cells.

Detailed description

PRIMARY OBJECTIVES: I. To characterize the safety and the toxicities of BAY 43-9006 (sorafenib) administered continuously twice daily by oral route in combination with CCI-779 (temsirolimus) administered intravenously once weekly in advanced solid malignancies. II. To determine the maximum-tolerated dose (MTD) and recommended dose for the phase II study (RD) of this regimen. III. To describe the pharmacokinetic behavior of BAY 43-9006 (sorafenib) and CCI-779 (temsirolimus) when combined. SECONDARY OBJECTIVES: I. To evaluate the relationship between pharmacokinetic (PK) parameters of exposure and drug effect on biological surrogates of proliferation, cell survival, differentiation and angiogenesis in peripheral blood mononuclear cells (PBMCs) and tumor tissue where the tumor is accessible for biopsy. II. To analyze the biologic effects of BAY 43-9006 and CCI-779 on downstream targets of the P13K/Akt/mTOR and Raf signaling pathways. III. To evaluate preliminary antitumor activity of the combination. OUTLINE: This is an open-label, dose-escalation study of temsirolimus. Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. They also receive oral sorafenib\* twice daily starting on day 8 of course 1. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. NOTE: \*On the days of the temsirolimus infusion, temsirolimus should be taken concurrently with the morning dose of sorafenib. 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. Up to 12 patients are treated at the MTD. After completion of study treatment, patients are followed for 4 weeks.

Conditions

• Unspecified Adult Solid Tumor, Protocol Specific

Interventions

Type	Name	Description
DRUG	sorafenib tosylate	Given orally
DRUG	temsirolimus	Given IV
OTHER	laboratory biomarker analysis	Correlative studies

Timeline

• Start date: 2005-09-01
• Primary completion: 2007-04-01
• Completion: 2007-04-01
• First posted: 2005-11-21
• Last updated: 2015-04-15

Locations

1 site across 1 country: United States