GTI-2040 and Gemcitabine in Treating Patients With Metastatic or Unresectable Solid Tumors

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.

Inclusion criteria

• Histologically or cytologically confirmed solid tumor

• Metastatic or unresectable disease for which standard curative or palliative measures do not exist or are no longer effective
• Measurable or evaluable disease
• No known active or progressive brain metastases or primary brain tumors
• Performance status - ECOG 0-2
• Performance status - Karnofsky 60-100%
• More than 12 weeks
• Hemoglobin > 9 g/dL
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Bilirubin ≤ 2 times upper limit of normal (ULN)
• AST and ALT ≤ 3 times ULN (5 times ULN if hepatic metastases are present)
• Creatinine ≤ 2.0 mg/dL
• Creatinine clearance ≥ 50 mL/min
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior allergic reaction attributed to compounds of similar chemical or biological composition to study drugs
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other condition (e.g., dementia or developmental delay) that would preclude giving informed consent
• No other concurrent uncontrolled illness that would preclude study participation
• Prior biologic therapy allowed
• No concurrent biologic therapy
• No concurrent immunotherapy
• No concurrent routine filgrastim (G-CSF) or sargramostim (GM-CSF)
• Prior gemcitabine allowed
• Prior investigational chemotherapy allowed
• At least 4 weeks since prior chemotherapy (6 weeks for mitomycin, carmustine, or nitrosoureas) and recovered
• No other concurrent chemotherapy
• Concurrent hormonal therapy (e.g., luteinizing hormone-releasing hormone agonists) for prostate cancer is allowed
• At least 4 weeks since prior radiotherapy and recovered
• No prior radiotherapy to more than 25% of bone marrow
• No concurrent radiotherapy
• Recovered from prior surgery
• No other concurrent investigational therapy
• No other concurrent anticancer therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent long-term oral anticoagulation therapy (e.g., warfarin)

• Prophylactic warfarin to maintain central venous access patency allowed