Phase II trial to study the effectiveness of combining suramin, paclitaxel, and carboplatin
in treating patients who have stage IIIB or stage IV non-small cell lung cancer. Drugs used
in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or
die. Combining more than one drug may kill more tumor cells.
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
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.
- 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