NCT00119236

17-AAG and Irinotecan in Treating Patients With Locally Advanced or Metastatic Solid Tumors

An Open-Labeled Non-Randomized Phase I Study of 17-N-allylamino-17-demethoxy Geldanamycin (17AAG) Administered With Irinotecan (CPT-11) in Patients With Advanced Solid Tumors

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 48 (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 17-AAG and irinotecan in treating patients with locally advanced or metastatic solid tumors. Drugs used in chemotherapy, such as 17-AAG and irinotecan, work in different ways to stop the growth of tumor cells either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

Detailed description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of combined 17AAG and irinotecan given weekly for two weeks in a 21-day cycle that can be used for future phase II studies. SECONDARY OBJECTIVES: I. To explore the effects of the combination on the expression of Hsp90 client proteins in peripheral mononuclear cells and tumor tissues. Tumor biopsies will be performed before and after 17AAG treatment in 12 patients at the MTD ("Expanded Cohort") only. II. To investigate the clinical pharmacokinetics of intravenous 17AAG, irinotecan, and their metabolites, in this combination. III. To obtain preliminary data on the therapeutic activity of 17AAG in combination with irinotecan in patients with advanced solid tumors. IV. To obtain preliminary result in the relationship between tumor response and p53-status. OUTLINE: This is an open-label, non-randomized, dose-escalation study. Patients receive irinotecan IV over 30 minutes followed by 17-N-allylamino-17-demethoxygeldanamycin (17-AAG)\* IV over 2 hours on days 1 and 8. Treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving stable or improved disease after course 2 may receive additional courses of treatment. NOTE: \*17-AAG is administered on days 2 and 8 during course 2 for patients treated at non-maximum tolerated doses (MTD) (dose-escalation portion) and on day 8 only during course 1 for patients treated at the MTD (expanded cohort).Cohorts of 3-6 patients receive escalating doses of 17-AAG and irinotecan until the 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. An additional 12 patients are treated at the MTD.

Conditions

• Unspecified Adult Solid Tumor, Protocol Specific

Interventions

Type	Name	Description
DRUG	tanespimycin
DRUG	irinotecan hydrochloride

Timeline

• Start date: 2005-05-01
• Primary completion: 2008-10-01
• First posted: 2005-07-13
• Last updated: 2013-06-04

Locations

1 site across 1 country: United States