RATIONALE: Drugs used in chemotherapy such as docetaxel and gemcitabine use different ways to stop tumor cells from dividing so they stop growing or die. Some tumors become resistant to chemotherapy drugs. Combining suramin with either docetaxel or gemcitabine may reduce resistance to the drugs and kill more tumor cells.

PURPOSE: Randomized phase I trial to compare the effect on the body of suramin combined with either docetaxel or gemcitabine and to determine its effectiveness in treating patients who have stage IIIB or stage IV non-small cell lung cancer that is refractory to platinum chemotherapy (such as cisplatin, carboplatin, or oxaliplatin).

Condition	Treatment or Intervention	Phase
recurrent non-small cell lung cancer stage IIIB non-small cell lung cancer stage IV non-small cell lung cancer	Drug: docetaxel  Drug: gemcitabine  Drug: suramin  Procedure: anti-cytokine therapy  Procedure: biological response modifier therapy  Procedure: chemosensitization/potentiation  Procedure: chemotherapy  Procedure: drug resistance inhibition  Procedure: growth factor antagonist therapy	Phase I

OBJECTIVES:

• Determine the safety of low-dose suramin administered with docetaxel or gemcitabine in patients with stage IIIB or IV platinum-refractory non-small cell lung cancer.
• Determine, preliminarily, the antitumor activity of these regimens in these patients.
• Determine whether suramin plasma concentrations in combination with docetaxel or gemcitabine can be predicted by pretreatment dose calculations based on clinical parameters.

OUTLINE: This is a randomized, pilot, dose-finding study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive low-dose suramin IV over 30 minutes and docetaxel IV over 1 hour on day 1.
• Arm II: Patients receive low-dose suramin IV over 30 minutes and gemcitabine IV over 30 minutes on days 1 and 8. In both arms, treatment repeats every 3 weeks for 3 courses in the absence of unacceptable toxicity. Patients with complete or partial response after the initial 3 courses optionally continue the same therapy for 3 additional courses. Patients with disease progression after 6 courses of treatment on the original arm may cross over and receive treatment on the other arm. Patients with progressive disease or stable disease after the initial 3 courses cross over to the other arm and receive treatment on that arm for 3 additional courses. Patients with responsive or stable disease after the sixth course may continue therapy on that arm.

Cohorts of 6-12 patients in each arm receive doses of suramin calculated from a clinical formula validated in prior clinical trials. Adjustments on the suramin dose are performed if the initial dose is off target and less than 50 µM peak concentration. The optimal dose is defined as the dose at which at least 5 of 6 patients achieve optimal plasma concentrations of suramin and no more than 1 of 6 patients experiences dose-limiting toxicity. In the event of dose-limiting toxicity, doses of docetaxel and gemcitabine are adjusted until the optimal dose in combination with suramin is determined.

Patients are followed for at least 30 days.

PROJECTED ACCRUAL: A total of 12-24 patients (6-12 per treatment arm) will be accrued for this study within 6 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer
• Stage IIIB* or IV NOTE: *Must not be amenable to concurrent radiotherapy and chemotherapy (e.g., presence of pleural effusion or low pulmonary reserve)
• Progressive disease after prior platinum-containing regimen (e.g., cisplatin, carboplatin, or oxaliplatin)
• No known brain or leptomeningeal disease, unless all of the following are true:
• Lesions were previously irradiated
• No concurrent corticosteroids
• No clinical symptoms

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9.0 g/dL

Hepatic

• Bilirubin no greater than 1.5 mg/dL
• AST/ALT no greater than 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2.5 times ULN

Renal

• Creatinine no greater than 2.0 mg/dL

Cardiovascular

• No myocardial infarction within the past 6 months
• No congestive heart failure requiring therapy
• No unstable angina

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active serious infectious process
• No grade 2 or greater neuropathy
• No uncontrolled diabetes mellitus
• No psychiatric disorder that would preclude giving informed consent or interfere with study follow-up

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• At least 28 days since prior cytotoxic chemotherapy and recovered
• No more than 2 prior chemotherapy regimens
• No prior docetaxel
• No prior gemcitabine

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• See Disease Characteristics
• Prior radiotherapy allowed

Surgery

• Not specified

Other

• At least 2 weeks since prior epidermal growth factor receptor therapy
• Prior suramin allowed
• No concurrent anti-HIV medications for HIV-positive patients

Ohio
      Arthur G. James Cancer Hospital at Ohio State University, Columbus,  Ohio,  43210-1240,  United States; Recruiting

Study chairs or principal investigators

Miguel A. Villalona-Calero, MD,  Principal Investigator,  Arthur G. James Cancer Hospital & Richard J. Solove Research Institute   

Study ID Numbers:  CDR0000318808; OSU-NCI-5889; NCI-5889
Record last reviewed:  September 2003
Record first received:  August 6, 2003
ClinicalTrials.gov Identifier:  NCT00066768
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-08