NCT00372736

AEG35156 and Docetaxel in Treating Patients With Locally Advanced, Metastatic, or Recurrent Solid Tumors

A Phase I Study of AEG35156 Given as a 2 Hour Intravenous Infusion in Combination With Docetaxel in Patients With Solid Tumours

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 27 (actual)
• Sponsor: NCIC Clinical Trials Group · Network
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. AEG35156 may help docetaxel work better by making tumor cells more sensitive to the drug. PURPOSE: This phase I trial is studying the side effects and best dose of AEG35156 when given together with docetaxel in treating patients with locally advanced, metastatic, or recurrent solid tumors.

Detailed description

OBJECTIVES: Primary * Determine the maximum tolerated dose and define a recommended phase II dose of AEG35156 in combination with docetaxel in patients with locally advanced, metastatic, or recurrent solid tumors. Secondary * Determine the qualitative and quantitative toxicities of AEG35156 in combination with docetaxel given and define the duration and reversibility of those toxicities. * Determine the pharmacokinetic profile of this regimen. * Assess, preliminarily, the antitumor activity of this regimen in these patients. * Assess the pharmacodynamic effects of AEG35156 on X-linked inhibitor of apoptosis levels and apoptosis in peripheral blood mononuclear cells and in tumor tissue of these patients. * Evaluate M30/M65 cytokeratin 18 level (a marker of apoptosis/necrosis of epithelial tumors) in serum of these patients. OUTLINE: This is a multicenter, open-label, dose-escalation study of AEG35156. Patients receive AEG35156 IV over 2 hours on days -1, 0, 1, 8, and 15 during course 1 and on days 1, 8, and 15 of all subsequent courses. Patients also receive docetaxel IV over 1 hour on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of AEG35156 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. Additional patients receive AEG35156 at the recommended phase II dose (RPTD). Blood is drawn periodically for pharmacokinetic and pharmacodynamic studies. Samples are examined by flow cytometry, immunoenzyme methods, and reverse transcriptase-polymerase chain reaction for biological markers. Tumor tissue (archival and fresh) is collected from patients treated at the RPTD and examined by immunohistochemical methods and biological marker analysis. After completion of study treatment, all patients are followed at 4 weeks. Patients with response or stable disease ongoing are followed every 3 months thereafter until relapse/progression. Patients with protocol-related toxicity also followed q 3 months until resolution to ≤ grade 2. 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	AEG35156	After a recommended phase II dose (RPTD) of AEG35156 has been determined with docetaxel 75 mg/m2, patients will be accrued to the RPTD-1 plus docetaxel 100 mg/m2, and possibly RPTD plus docetaxel 100 mg/m2, to determine the RPTD of AEG35156 in combination with docetaxel 100 mg/m2 given every three weeks.
DRUG	docetaxel	After a recommended phase II dose (RPTD) of AEG35156 has been determined with docetaxel 75 mg/m2, patients will be accrued to the RPTD-1 plus docetaxel 100 mg/m2, and possibly RPTD plus docetaxel 100 mg/m2, to determine the RPTD of AEG35156 in combination with docetaxel 100 mg/m2 given every three weeks.
GENETIC	protein expression analysis	Cycle 1: Pre-dose on Days -2, 1, 8 and 15; repeat every 2-4 days if LFTs \> 5 x ULN1 Cycle 2: Prior to each infusion; repeat every 2-4 days if LFTs \> 5 x ULN1
GENETIC	reverse transcriptase-polymerase chain reaction	Data will be summarized by descriptive statistics relevant to each of the proposed pharmacodynamic studies.
OTHER	flow cytometry	Data will be summarized by descriptive statistics relevant to each of the proposed pharmacodynamic studies.
OTHER	immunoenzyme technique	Data will be summarized by descriptive statistics relevant to each of the proposed pharmacodynamic studies.
OTHER	immunohistochemistry staining method	The plasma concentration/ time data will be analysed using non-compartmental methods. The pharmacokinetic parameters to be determined for AEG35156 include the maximum observed plasma concentration (Cmax), the half-life (T1/2), and mean residence time (MRT).
OTHER	laboratory biomarker analysis	The plasma concentration/ time data will be analysed using non-compartmental methods. The pharmacokinetic parameters to be determined for AEG35156 include the maximum observed plasma concentration (Cmax), the half-life (T1/2), and mean residence time (MRT).

Timeline

• Start date: 2006-07-27
• Primary completion: 2009-03-24
• Completion: 2012-01-06
• First posted: 2006-09-07
• Last updated: 2023-08-04

Locations

3 sites across 1 country: Canada