OGX-011 and Docetaxel in Treating Patients With Metastatic or Locally Recurrent Solid Tumors
RATIONALE: OGX-011 may kill tumor cells by blocking some of the proteins that may cause tumor cells to grow. 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. Giving OGX-011 together with docetaxel may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of OGX-011 when given together with docetaxel in treating patients with metastatic or locally recurrent solid tumors.
Unspecified Adult Solid Tumor, Protocol Specific
Drug: custirsen sodium
Other: pharmacological study
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of a Second Generation Clusterin Antisense Oligonucleotide (OGX-011) in Combination With Docetaxel|
- Dose-limiting toxicity [ Designated as safety issue: Yes ]
- Recommended phase II dose of OGX-011 [ Designated as safety issue: Yes ]
- Pharmacokinetic profile [ Designated as safety issue: No ]
- Serum clusterin levels and clusterin expression in peripheral blood mononuclear cells and accessible tumors [ Designated as safety issue: No ]
- Objective response [ Designated as safety issue: No ]
|Study Start Date:||March 2003|
|Study Completion Date:||December 2009|
- Determine the dose-limiting toxicity and recommended phase II dose of OGX-011 when administered with docetaxel in patients with metastatic or locally recurrent solid tumors.
- Determine the pharmacokinetic profile of this regimen in these patients.
- Assess the effect of OGX-011 on serum clusterin levels and clusterin expression in peripheral blood mononuclear cells and accessible tumors.
- Assess objective response in patients treated with this regimen.
OUTLINE: This is an open-label, multicenter, dose-escalation study of OGX-011. Patients are sequentially assigned to 1 of 2 treatment schedules.
- Schedule A: Patients receive OGX-011 IV over 2 hours on days 1, 3, 5, 8, 15, 22, 29, and 36 of course 1 and once weekly in weeks 1-6 of all subsequent courses. Patients also receive docetaxel IV over 1 hour once weekly in weeks 1-5. Treatment repeats every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
- Schedule B: Patients receive OGX-011 IV over 2 hours on days -7, -5, -3, 1, 8, and 15 of course 1 and days 1, 8, and 15 of all subsequent courses. Patients also receive docetaxel IV over 1 hour on day 1. Treatment repeats every 3 weeks (course 1 is 4 weeks in duration) for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of OGX-011 (in each schedule) until the recommended phase II dose (RPTD) is determined. The RPTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients undergo serum collection periodically for pharmacokinetic and pharmacodynamic analysis.
After completion of study treatment, patients are followed at 4 weeks and then every 3 months thereafter.
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.