S0124: Cisplatin Combined With Irinotecan or Etoposide For Extensive-Stage Small Cell Lung Cancer

SWOG Cancer Research Network

Status and phase: Completed; Phase 3

Conditions: Lung Cancer

Treatments: Drug: etoposide; Drug: cisplatin; Drug: irinotecan hydrochloride

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00045162

CDR0000256908

S0124 (Other Identifier)

U10CA032102 (U.S. NIH Grant/Contract)

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 whether cisplatin combined with irinotecan is more effective than cisplatin combined with etoposide in treating extensive-stage small cell lung cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of cisplatin combined with either irinotecan or etoposide in treating patients who have extensive-stage small cell lung cancer.

Full description

OBJECTIVES:

• Compare the survival of patients with extensive stage small cell lung cancer treated with cisplatin and irinotecan vs cisplatin and etoposide.
• Compare the objective response rate and progression-free survival of patients treated with these regimens.
• Compare the toxic effects of these regimens in these patients.
• Determine the association between UGT1A1 polymorphisms and irinotecan-associated toxic effects in these patients.
• Determine the association between ERCC-1 and XRCC-1 polymorphisms and non-response of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to number of metastatic sites (single vs multiple), lactic dehydrogenase (no greater than upper limit of normal (ULN) vs greater than ULN), and weight loss in the past 6 months (5% or less vs more than 5%). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive irinotecan IV over 90 minutes on days 1, 8, and 15 and cisplatin IV over 30-60 minutes on day 1. Courses repeat every 4 weeks.
• Arm II: Patients receive etoposide IV over 30-60 minutes on days 1-3 and cisplatin IV over 30-60 minutes on day 1. Courses repeat every 3 weeks.

Treatment in both arms continues for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 620 patients (310 per treatment arm) will be accrued for this study within 4 years.

Enrollment: 671 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed extensive stage small cell lung cancer (SCLC)
• Measurable or evaluable disease by CT scan, MRI, x-ray, physical exam, or nuclear exam
• Brain metastases allowed if previously treated with radiotherapy and/or surgery and are neurologically stable (i.e., no progressing symptoms and off steroids and anticonvulsants)

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC at least 3,000/mm^3
• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST or ALT no greater than 2.5 times ULN

Renal

• Creatinine normal
• Creatinine clearance at least 50 mL/min

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• 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
• HIV negative
• No concurrent AIDS-related illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior biologic therapy for SCLC
• No filgrastim (G-CSF) within 24 hours of chemotherapy

Chemotherapy

• No prior systemic chemotherapy for SCLC

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• See Disease Characteristics
• At least 21 days since prior brain radiotherapy and recovered
• No other prior radiotherapy for SCLC

Surgery

• See Disease Characteristics
• At least 21 days since prior thoracic or other major surgery and recovered

Other

• No concurrent enzyme inducing antiepileptic drugs (phenytoin, phenobarbital, oxcarboxepine, or carbamazepine)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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671 participants in 2 patient groups

1

Active Comparator group

Treatment:

Drug: cisplatin

Drug: irinotecan hydrochloride

2

Active Comparator group

Treatment:

Drug: etoposide

Drug: cisplatin