Combination Chemotherapy With or Without Tirapazamine in Treating Patients With Stage IIIB or Stage IV Non-small Cell Lung Cancer

SWOG Cancer Research Network

Status and phase

Completed

Phase 3

Conditions

Lung Cancer

Treatments

Drug: tirapazamine

Drug: carboplatin

Drug: paclitaxel

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT00006484

CDR0000068315

SWOG-S0003

Details and patient eligibility

About

RATIONALE: 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. It is not yet known which combination chemotherapy regimen is more effective for non-small cell lung cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of carboplatin plus paclitaxel with or without tirapazamine in treating patients who have stage IIIB or stage IV non-small cell lung cancer.

Full description

OBJECTIVES:

Compare the effects of paclitaxel and carboplatin with or without tirapazamine on progression-free survival and overall survival in patients with stage IV and selected stage IIIB non-small cell lung cancer.
Compare response rates in patients treated with these regimens.
Compare the toxic effects of these regimens in these patients.

OUTLINE: This is a randomized study. Patients are stratified according to weight loss (less than 5% vs 5% or more), stage of disease (IIIB vs IV), and lactate dehydrogenase level (normal vs abnormal). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive tirapazamine IV over 2 hours followed by paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1.
Arm II: Patients receive paclitaxel and carboplatin as in arm I. Treatment continues every 21 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for one year, and then every 6 months for 2 years, or until death.

PROJECTED ACCRUAL: Approximately 500 patients (250 per arm) will be accrued for this study within 20 months.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically proven newly diagnosed advanced primary non-small cell lung cancer (NSCLC), including the following cellular types:
- Adenocarcinoma
- Large cell carcinoma
- Squamous cell carcinoma
- Unspecified carcinoma OR
Recurrent disease after prior surgery and/or radiotherapy
Stage IIIB disease
- T4 lesion due to malignant pleural effusion OR
Stage IV disease
- Any T, any N, M1 (distant metastasis, including lesions in multiple lobes of the ipsilateral lung)
Measurable or evaluable disease
- Pleural effusions, ascites, and laboratory parameters not considered as only evidence of disease
- Must be outside prior radiated field or area of prior surgical resection or new lesion must be present
No known brain metastases

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

Zubrod 0-1

Life expectancy:

Not specified

Hematopoietic:

Absolute granulocyte count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Hemoglobin at least 9 g/dL

Hepatic:

Bilirubin no greater than 2 times upper limit of normal (ULN)
SGOT or SGPT no greater than 2 times ULN
Alkaline phosphatase no greater than 2 times ULN

Renal:

Creatinine no greater than ULN
Creatinine clearance at least 50 mL/min

Other:

Not pregnant or nursing
Fertile patients must use effective contraception
No peripheral neuropathy (motor or sensory) of grade 2 or greater
No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or stage I/II cancer in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy: