Suramin, Paclitaxel, and Carboplatin in Treating Patients With Stage IIIB or Stage IV Non-small Cell Lung Cancer

PRIMARY OBJECTIVES:

I. Determine the minimum effective dose of suramin that will reduce resistance to chemotherapy with paclitaxel and carboplatin in patients with stage IIIB or IV non-small cell lung cancer (phase I). (Phase I closed to accrual 1/29/02).

II. Evaluate pharmacokinetic interactions of this drug combination in these patients (phase I). (Phase I closed to accrual 1/29/02).

III. Determine the objective response rate in patients treated with this regimen (phase II [chemotherapy-naive patients closed to accrual 9/1/03]).

IV. Determine the time to tumor progression, progression-free rate at 6 months, and 1-year survival of patients treated with this regimen (phase II [chemotherapy-naive patients closed to accrual 9/1/03]).

OUTLINE: Patients in phase II are stratified according to prior treatment (chemotherapy naive [closed to accrual 9/1/03] vs chemotherapy refractory). Phase I (phase I closed to accrual 1/29/02):

Patients receive suramin IV over 30 minutes on days 1 and 2. Patients also receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of suramin until the target dose is determined. The target 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 exceed optimal level. Doses of paclitaxel are adjusted until the maximum tolerated dose in combination with suramin and paclitaxel is determined.

Phase II (chemotherapy-naive patients closed to accrual 9/1/03): Patients receive the target dose of suramin IV over 30 minutes on days 1 and 2. Patients also receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3-6 weeks.

PROJECTED ACCRUAL: Approximately 82 patients (18 for phase I [phase I closed to accrual 1/29/02] and 64 for phase II [chemotherapy-naive patients closed to accrual 9/1/03]) will be accrued for this study.

Inclusion criteria

• Histologically or cytologically confirmed advanced non-small cell lung cancer

• Stage IIIB not amenable to concurrent chemotherapy or radiotherapy (e.g., pleural effusion or low pulmonary reserve)
• Stage IV
• Measurable disease
• Meets criteria for 1 of the following:

• Chemotherapy naive (phases I and II) (phase I closed to accrual 1/29/02) (phase II [chemotherapy-naive patients] closed to accrual 9/1/03)
• Previously treated (phase I) (phase I closed to accrual 1/29/02)

• Received no more than 1 prior chemotherapy regimen
• Chemotherapy refractory, defined as disease progression during or within 3 months after carboplatin/paclitaxel chemotherapy (phase II)
• No known brain or leptomeningeal disease unless previously irradiated, currently not undergoing corticosteroid therapy, and clinically asymptomatic
• Performance status - ECOG 0-2
• At least 12 weeks
• Absolute neutrophil count at least 1,500/mm^3
• Hemoglobin at least 9.0 g/dL
• Platelet count at least 100,000/mm^3
• Bilirubin no greater than 1.5 mg/dL
• AST and ALT no greater than 2.5 times upper limit of normal
• Creatinine no greater than 1.5 mg/dL
• Creatinine clearance at least 50 mL/min
• Calcium less than 11.5 mg/dL
• No history of myocardial infarction within the past 6 months
• No history of congestive heart failure requiring therapy
• No history of unstable angina
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active serious infection
• HIV negative
• No concurrent uncontrolled diabetes mellitus
• No known hypersensitivity to Cremophor EL
• No grade 2 or greater neuropathy
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No known psychiatric condition that would preclude study compliance
• At least 28 days since prior cytotoxic chemotherapy and recovered
• Prior radiotherapy allowed except to indicator lesion