NCT00275093

Temsirolimus in Treating Patients With Metastatic Solid Tumor or Lymphoma That Cannot Be Removed By Surgery Who Have Different Levels of Liver Function

A Phase I Pharmacokinetic and Pharmacodynamic Study of Temsirolimus (CCI-779) in Patients With Advanced Malignancies and Normal and Impaired Liver Function: An NCI Organ Dysfunction Working Group Study

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 130 (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 in treating patients with metastatic solid tumor or lymphoma that cannot be removed by surgery who have different levels of liver function. Temsirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Temsirolimus may have different effects in patients who have changes in their liver function

Detailed description

PRIMARY OBJECTIVES: I. To evaluate the safety, tolerability, and to establish the maximum tolerated recommended dose (RD) CCI-779 (temsirolimus) in cohorts of patients with varying degrees of hepatic dysfunction (mild, moderate, and severe) in order to provide appropriate dosing recommendations for CCI-779 (temsirolimus) in this population. SECONDARY OBJECTIVES: I. To characterize the pharmacokinetic (PK) profile of CCI-779 (temsirolimus) in patients with varying degrees of hepatic function. II. To determine if the pharmacodynamic (PD) profile of CCI-779 (temsirolimus) as measured by drug effects on p70s6 kinase and p4EBP1 phosphorylation and other markers of mTOR inhibition in peripheral blood mononuclear cells (PBMC) is altered in patients with varying degrees of hepatic function. III. To document the non-dose limiting toxicities and any anti-tumor efficacy associated with administration of CCI-779 (temsirolimus) in this patient population. IV. To compare the NCI ODWG criteria and the Child-Pugh classification of hepatic dysfunction in terms of their predictive value in reducing interpatient variability in the PK and PD of CCI-779 (temsirolimus). OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to hepatic function (normal vs mild dysfunction vs moderate dysfunction vs severe dysfunction vs liver transplant). Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Courses repeat 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. Up to 12 patients are treated at the MTD. After completion of study treatment, patients are followed periodically for 30 days.

Conditions

• Hepatic Complications
• Lymphoma
• Unspecified Adult Solid Tumor, Protocol Specific

Interventions

Type	Name	Description
DRUG	temsirolimus	Given IV
OTHER	laboratory biomarker analysis	Correlative studies
OTHER	pharmacological study	Correlative studies

Timeline

• Start date: 2005-12-01
• Primary completion: 2008-03-01
• First posted: 2006-01-11
• Last updated: 2013-01-30

Locations

1 site across 1 country: United States