Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Cisplatin Combined With Either Irinotecan or Etoposide in Treating Patients With Extensive-Stage Small Cell Lung Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	18 and over	NCI	SWOG-S0124 NCCTG-S0124, CALGB-S0124, S0124, NCT00045162

Special Category: CTSU trial

Objectives

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

Entry 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)

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)

Patient Characteristics:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC at least 3,000/mm³
• Absolute granulocyte count at least 1,500/mm³
• Platelet count at least 100,000/mm³

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

Expected Enrollment

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

Outcomes

Survival

Objective response rate
Toxicity
Time to tumor progression

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.

Lara PN Jr, Natale R, Crowley J, et al.: Phase III Trial of Irinotecan/Cisplatin Compared With Etoposide/Cisplatin in Extensive-Stage Small-Cell Lung Cancer: Clinical and Pharmacogenomic Results From SWOG S0124. J Clin Oncol : , 2009.[PUBMED Abstract]

Natale RB, Lara PN, Chansky K, et al.: S0124: A randomized phase III trial comparing irinotecan/cisplatin (IP) with etoposide/cisplatin (EP) in patients (pts) with previously untreated extensive stage small cell lung cancer (E-SCLC). [Abstract] J Clin Oncol 26 (Suppl 15): A-7512, 2008.

Hanna N, Bunn PA Jr, Langer C, et al.: Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol 24 (13): 2038-43, 2006.[PUBMED Abstract]

Hanna NH, Einhorn L, Sandler A, et al.: Randomized, phase III trial comparing irinotecan/cisplatin (IP) with etoposide/cisplatin (EP) in patients (pts) with previously untreated, extensive-stage (ES) small cell lung cancer (SCLC). [Abstract] Proceedings of the American Society of Clinical Oncology 23 (Suppl 16): A-LBA7004, 622s, 2005.

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

Ronald Natale, MD, Study coordinator		Ph: 310-423-1101
David Gandara, MD, Study coordinator		Ph: 916-734-3772 Email: david.gandara@ucdmc.ucdavis.edu
Primo Lara, MD, Study coordinator		Ph: 916-734-3771

North Central Cancer Treatment Group

James Jett, MD, Study coordinator		Ph: 507-284-2511

Cancer and Leukemia Group B

Jane Carleton, MD, Study coordinator		Ph: 516-734-8966 Email: jcarleto@nshs.edu

Registry Information
Official Title		Randomized Phase III Trial of Cisplatin (NSC-119875) and Irinotecan (NSC-616348) Versus Cisplatin and Etoposide (NSC-141540) in Patients with Extensive Stage Small Cell Lung Cancer (E-SCLC)
Trial Start Date		2002-11-01
Registered in ClinicalTrials.gov		NCT00045162
Date Submitted to PDQ		2002-06-28
Information Last Verified		2007-03-01
NCI Grant/Contract Number		CA32102