OBJECTIVES:

• 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).
• Determine the toxicity of this regimen in these patients.
• Determine the objective tumor response rate in patients treated with this regimen.
• Determine the stable disease rate, time to disease progression, objective response duration, and duration of stable disease in patients treated with this regimen.
• Determine the pharmacokinetics of GTI-2040 when administered in combination with docetaxel in these patients.
• Correlate the pharmacokinetics of GTI-2040 with the biological and toxic effects of this regimen in these patients.
• 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 regimen.

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.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed diagnosis of 1 of the following:

  • Solid tumor malignancy (phase I only)*
  • Prostate cancer (phase I only)*
  • Non-small cell lung cancer (phase I and II)* NOTE: *Phase I study closed to accrual as of 8/5/2004
• Recurrent, metastatic, locally advanced unresectable, or treatment-refractory disease

• Measurable disease

  • At least 1 unidimensionally measurable lesion at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
  • Previously irradiated lesions are considered measurable provided they have demonstrated progression before study entry

  • No bone-only disease

    • Must have measurable disease other than bone lesions
• No stage IIIA or IIIB non-small cell lung cancer without a malignant pleural or pericardial effusion that is eligible for first-line radical combined chemotherapy and radiotherapy

• No known progressive or symptomatic brain metastases

  • Asymptomatic brain metastases allowed

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 3 months

Hematopoietic

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• No history of coagulopathy

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST/ALT no greater than 2 times ULN (3.5 times ULN if liver metastases are present)
• INR no greater than 1.3
• APTT no greater than 1.25 times ULN

Renal

• Creatinine no greater than 1.5 times ULN OR
• Creatinine clearance at least 50 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No evidence of cardiac dysfunction
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active peptic ulcer disease
• No poorly controlled diabetes mellitus
• No pre-existing grade 2 or greater neuropathy
• No ongoing or active infection
• No contraindication to corticosteroids
• No psychiatric illness or social situation that would limit compliance with study requirements
• No prior allergic reaction attributed to compounds of similar chemical or biological composition to study drugs
• No other concurrent uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• One, and only one, prior chemotherapy regimen for advanced disease (not including adjuvant therapy) allowed

  • Neoadjuvant/adjuvant chemotherapy allowed
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and recovered

Endocrine therapy

• Prior multiple lines of endocrine therapy for advanced solid tumors allowed
• More than 4 weeks since prior endocrine therapy and recovered
• Concurrent steroids allowed

Radiotherapy

• See Disease Characteristics
• More than 4 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy to sole site of measurable disease

Surgery

• Prior surgery allowed

Other

• No concurrent anticoagulant therapy

  • Concurrent low-dose warfarin for central line thrombosis prophylaxis allowed
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational or commercial agents or therapies intended to treat the malignancy
• Concurrent bisphosphonates allowed