A Phase I/2 Study of GTI-2040 Combined With Docetaxel In Metastatic Or Unresectable Locally Advanced Non-Small Cell Lung Cancer
I. Determine the recommended phase II dose of GTI-2040 and docetaxel in patients with
recurrent, metastatic, or unresectable locally advanced non-small cell lung cancer, prostate
cancer, or other solid tumors (phase I study closed to accrual as of 8/5/2004).
II. Determine the toxicity of this regimen in these patients. III. Determine the objective
tumor response rate in patients treated with this regimen.
IV. Determine the stable disease rate, time to disease progression, objective response
duration, and duration of stable disease in patients treated with this regimen.
V. Determine the pharmacokinetics of GTI-2040 when administered in combination with
docetaxel in these patients.
VI. Correlate the pharmacokinetics of GTI-2040 with the biological and toxic effects of this
regimen in these patients.
VII. Correlate baseline and post-treatment levels of ribonucleotide reductase activity in
tumor biopsies and peripheral blood mononuclear cells and tumoral expression of c-myc, ras,
pRAF1, pMAPK, and markers of apoptosis with clinical outcome in patients treated with this
OUTLINE: This is an open-label, dose-escalation, multicenter study.
Phase I (closed to accrual as of 8/5/2004): Patients receive GTI-2040 IV continuously on
days 1-14. Patients also receive docetaxel IV over 1 hour on day 3 during course 1 and on
day 1 for all subsequent courses. Courses repeat every 21 days in the absence of disease
progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of GTI-2040 and docetaxel until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 3 or 2 of 6
patients experience dose-limiting toxicity. The recommended phase II dose (RP2D) is defined
as the dose preceding the MTD.
Phase II: Patients receive GTI-2040 and docetaxel at the RP2D as in phase I.
Patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 12-48 patients (12-18 for phase I [closed to accrual as of
8/5/2004] and 15-30 for phase II) will be accrued for this study within 4-16 months.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of patients experiencing dose limiting toxicities (DLTs), graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 (Phase I)
Up to day 21
Princess Margaret Hospital Phase 2 Consortium
United States: Food and Drug Administration