This phase I trial is studying the side effects and best dose of GTI-2040 and gemcitabine in treating patients with metastatic or unresectable solid tumors. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. GTI-2040 may stop the growth of tumor cells by blocking the enzymes necessary for their growth and by making tumor cells more sensitive to gemcitabine
OBJECTIVES: Primary I. Determine the toxicity profile and maximum tolerated dose of GTI-2040 and gemcitabine in patients with metastatic or unresectable solid tumors. Secondary I. Determine the pharmacokinetics and pharmacodynamics of this regimen in these patients. OUTLINE: This is an open-label, dose-escalation study. Patients receive GTI-2040 IV continuously on days 2-16 of course 1 and on days 1-16 of all subsequent courses and gemcitabine IV over 30 minutes on days 1, 8, and 15 of course 1 and on days 2, 9, and 16 of all subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of GTI-2040 and gemcitabine 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. Once the MTD is determined, 10 additional patients are treated at that dose. PROJECTED ACCRUAL: Approximately 18-40 patients will be accrued for this study within 6-20 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
San Antonio, Texas, United States
Maximum tolerated dose (MTD) of GTI-2040 and gemcitabine hydrochloride, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v3.0
Time frame: Up to day 28
Adverse events, graded according to the NCI CTC v3.0
Time frame: Up to 2 years
Levels of gemcitabine triphosphate (dFdCTP) in terms of pharmacokinetics of gemcitabine hydrochloride
Time frame: Days 1, 2, 8, and 15 (course 1), days 1, 2, 9, and 16 (course 2)
Levels of ribonucleotide reductase R2 and protein expression
Student t-tests will be employed.
Time frame: Days 1, 2, 8, and 15 (course 1), days 1, 2, 9, and 16 (course 2)
Levels of apoptotic markers and cell cycle regulatory proteins
Student t-tests will be employed.
Time frame: Days 1, 2, 8, and 15 (course 1), days 1, 2, 9, and 16 (course 2)
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