RATIONALE: 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.

PURPOSE: 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.

OBJECTIVES:

Primary

• Determine the toxicity profile and maximum tolerated dose of GTI-2040 and gemcitabine in patients with metastatic or unresectable solid tumors.

Secondary

• 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.

• Biological: GTI-2040
• Drug: gemcitabine hydrochloride

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 12 weeks

Hematopoietic

• Hemoglobin > 9 g/dL
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ 2 times upper limit of normal (ULN)
• AST and ALT ≤ 3 times ULN (5 times ULN if hepatic metastases are present)

Renal

• Creatinine ≤ 2.0 mg/dL OR
• Creatinine clearance ≥ 50 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• 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 CONCURRENT THERAPY:

Biologic therapy

• Prior biologic therapy allowed
• No concurrent biologic therapy
• No concurrent immunotherapy
• No concurrent routine filgrastim (G-CSF) or sargramostim (GM-CSF)

Chemotherapy

• 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

Endocrine therapy

• Concurrent hormonal therapy (e.g., luteinizing hormone-releasing hormone agonists) for prostate cancer is allowed

Radiotherapy

• At least 4 weeks since prior radiotherapy and recovered
• No prior radiotherapy to more than 25% of bone marrow
• No concurrent radiotherapy

Surgery

• Recovered from prior surgery

Other

• 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