NCT00368914

Sirolimus in Treating Patients With Metastatic or Unresectable Solid Tumors

Pharmacodynamic-Guided Dose Finding Study of Rapamycin (Rapamune®, Sirolimus) in Adult Patients With Solid Tumors

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Sirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I trial is studying the side effects and best dose of sirolimus in treating patients with metastatic or unresectable solid tumors.

Detailed description

OBJECTIVES: Primary * Determine the pharmacodynamic optimal dose of sirolimus, by evaluating p70\^s6 kinase inhibition in peripheral blood mononuclear cells (PBMC) and normal skin, in patients with metastatic or unresectable solid tumors. * Correlate target inhibition in tumor tissue with PBMC and normal skin target inhibition in patients whose tumors are amenable to sequential tumor biopsies. Secondary * Characterize the pharmacokinetics of sirolimus in these patients * Determine the pharmacodynamic effects of sirolimus on tumor, normal skin, and normal oral mucosa of these patients * Correlate the pharmacodynamic effects of sirolimus with pharmacokinetics and clinical effects. * Correlate the Akt signaling pathway with pharmacodynamic endpoints. * Explore pharmacokinetic-pharmacodynamic and toxicodynamic relationships of sirolimus in these patients. * Quantify the toxicity of sirolimus in these patients. * Evaluate, preliminarily, the activity of sirolimus in these patients. OUTLINE: This is a prospective, dose-escalation study. Patients receive oral sirolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of sirolimus 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. The pharmacodynamic optimal dose is considered the dose at which 10 patients are treated without requiring further dose escalation. Patients undergo blood collection, tumor tissue and normal skin biopsies, and oral mucosal smears periodically for pharmacodynamic, pharmacokinetic, and biomarker correlative studies. After completion of study treatment, patients are followed at 4 weeks. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Conditions

• Unspecified Adult Solid Tumor, Protocol Specific

Interventions

Type	Name	Description
DRUG	sirolimus
OTHER	laboratory biomarker analysis
OTHER	pharmacological study
PROCEDURE	biopsy

Timeline

• Start date: 2004-12-01
• Primary completion: 2009-06-01
• Completion: 2009-06-01
• First posted: 2006-08-29
• Last updated: 2010-08-09

Locations

1 site across 1 country: United States