S0124: Cisplatin Combined With Either Irinotecan or Etoposide in Treating Patients With Extensive-Stage Small Cell Lung Cancer - Full Text View

Purpose

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.

Condition	Intervention	Phase
Lung Cancer	Drug: cisplatin Drug: etoposide Drug: irinotecan hydrochloride	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Cisplatin Etoposide Irinotecan Irinotecan hydrochloride Etoposide phosphate

U.S. FDA Resources

Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:

Survival [ Time Frame: 0-3 years or until death ] [ Designated as safety issue: No ]
To compare the survival of patients with extensive stage small cell lung cancer (E-SCLC) treated with cisplatin and irinotecan versus cisplatin and etoposide.

Secondary Outcome Measures:

Objective response rate [ Time Frame: 0-3 years or until death ] [ Designated as safety issue: No ]
Toxicity [ Time Frame: Arm 1: every 28 days Arm 2: every 21 days ] [ Designated as safety issue: Yes ]
Time to tumor progression [ Time Frame: From date of registration until date of progression or date of death from any cause, whichever came first, assessed up to 3 years ] [ Designated as safety issue: No ]

Enrollment:	671
Study Start Date:	November 2002
Study Completion Date:	December 2009
Primary Completion Date:	March 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1	Drug: cisplatin Arm 1: 60 mg/m2 IV (over 30-60 min) on Day 1, Q 4 weeks x 4 Cycles Arm 2: 80 mg/m2 IV (over 30-60 min) on Day 1, Q 4 weeks x 4 Cycles Drug: irinotecan hydrochloride 60 mg/m2 IV (over 90 min)on Days 1, 8 & 15. Q 4 weeks x 4 Cycles
Active Comparator: 2	Drug: cisplatin Arm 1: 60 mg/m2 IV (over 30-60 min) on Day 1, Q 4 weeks x 4 Cycles Arm 2: 80 mg/m2 IV (over 30-60 min) on Day 1, Q 4 weeks x 4 Cycles Drug: etoposide 100 mg/m2 IV (over 30-60 min) on Days 1 , 2 & 3. Q 3 weeks x 4 Cycles

Detailed 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00045162

Show 408 Study Locations

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

North Central Cancer Treatment Group

Cancer and Leukemia Group B

Investigators

Principal Investigator:	Ronald B. Natale, MD	Cedars-Sinai Medical Center
Principal Investigator:	David R. Gandara, MD	University of California, Davis
Principal Investigator:	Primo N. Lara, MD	University of California, Davis
Principal Investigator:	James R. Jett, MD	Mayo Clinic
Principal Investigator:	Jane Carleton, MD	Don Monti Comprehensive Cancer Center at North Shore University Hospital

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Lara PN Jr, Natale R, Crowley J, Lenz HJ, Redman MW, Carleton JE, Jett J, Langer CJ, Kuebler JP, Dakhil SR, Chansky K, Gandara DR. 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 Apr 6; [Epub ahead of print]

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, Einhorn L, Guthrie T Jr, Beck T, Ansari R, Ellis P, Byrne M, Morrison M, Hariharan S, Wang B, Sandler A. 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. 2006 May 1;24(13):2038-43.

Lara P, Chansky K, Shibata T, et al.: Cisplatin + irinotecan versus cisplatin + etoposide in extensive stage small cell lung cancer (E-SCLC): Final "common arm": comparative outcomes analysis of JCOG 9511 and SWOG 0124. [Abstract] J Clin Oncol 27 (Suppl 15): A-8027, 2009.

Responsible Party:	Southwest Oncology Group
ClinicalTrials.gov Identifier:	NCT00045162 History of Changes
Other Study ID Numbers:	CDR0000256908, S0124, S0124, S0124, U10CA032102
Study First Received:	September 6, 2002
Last Updated:	November 15, 2012
Health Authority:	United States: Federal Government United States: Food and Drug Administration

Keywords provided by Southwest Oncology Group:

extensive stage small cell lung cancer

Additional relevant MeSH terms:

Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Etoposide phosphate
Irinotecan
Cisplatin

Etoposide
Camptothecin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 23, 2013