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

National Cancer Institute (NCI)

Status and phase

Completed

Phase 2

Conditions

Stage IIIB Non-small Cell Lung Cancer

Stage IV Non-small Cell Lung Cancer

Recurrent Non-small Cell Lung Cancer

Treatments

Drug: paclitaxel

Drug: carboplatin

Other: laboratory biomarker analysis

Other: pharmacological study

Drug: suramin

Study type

Interventional

Funder types

NIH

Identifiers

NCT00006929

NCI-2250

OSU 0045

U01CA076576 (U.S. NIH Grant/Contract)

OSU-00HO224

OSU-0045

NCI-2012-01403

CDR0000068345

Details and patient eligibility

About

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.

Full description

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.

Enrollment

82 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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