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

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ClinicalTrials.gov Identifier: NCT00045162
Recruitment Status : Completed
First Posted : January 27, 2003
Results First Posted : July 9, 2013
Last Update Posted : July 31, 2018
Sponsor:
Collaborators:
National Cancer Institute (NCI)
North Central Cancer Treatment Group
Cancer and Leukemia Group B
Information provided by (Responsible Party):
Southwest Oncology Group

Study Description
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Brief Summary:

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 or disease Intervention/treatment Phase
Lung Cancer Drug: cisplatin Drug: etoposide Drug: irinotecan hydrochloride Phase 3

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 671 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase III Trial of Cisplatin and Irinotecan (NSC-616348) Versus Cisplatin and Etoposide in Patients With Extensive Stage Small Cell Lung Cancer (E-SCLC)
Study Start Date : November 2002
Actual Primary Completion Date : March 2008
Actual Study Completion Date : December 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  1. Overall Survival [ Time Frame: Weekly while on treatment, then every 3 months for first year, then every 6 months unitl a maximum of 3 years from enrollment. ]
    Overall survival was defined as the duration between the date of randomization( enrollment) and the date of death due to any cause. Patients last known to be alive were censored at the date of last contact.


Secondary Outcome Measures :
  1. Progression-free Survival [ Time Frame: Every 6 weeks until disease progression or a maximum of 3 years from the date of enrollment. ]
    Progression-Free Survival was defined as the duration from the date of randomization (enrollment) until the date of documentation of progression as defined by RECIST (a 20% increase over nadir in the sum of longest diameters of target lesions, clear progression of a non-target lesion in the opinion of the treating investigator, appearance of new lesions, or symptomatic deterioration) or death due to any cause. Patients last known to be alive and without evidence of progression were censored at the date of last contact.

  2. Confirmed and Unconfirmed Complete and Partial Responses. [ Time Frame: Every 6 weeks while on protocol treatment for a maximum of 12 weeks ]
    Patients underwent chest CT/MRI every 6 weeks while on treatment and tumor response was evaluated by RECIST in the subset of patients with at least one target lesion at baseline. A target lesion was defined as a lesion with a longest diameter of at least 2 cm ( or at least 1 cm if by spiral CT). A complete response (CR) was defined as the disappearance of all disease, including non-target lesions. A partial response (PR) was defined as a 30% or greater decrease in the sum of the longest diameters. Confirmation of a CR or PR was defined as a second determination of CR or PR at least 4 weeks after the first determination.

  3. Number of Patients With a Given Type and Grade of Adverse Event. [ Time Frame: Every 4 weeks while subject on protocol treatment for a maximum of 12 weeks. ]
    Only adverse events that are possibly, probably or definitely related to study drug are reported. Only patients who received protocol treatment and were assessed for adverse events are included.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00045162


Locations
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Sponsors and Collaborators
Southwest Oncology Group
National Cancer Institute (NCI)
North Central Cancer Treatment Group
Cancer and Leukemia Group B
Investigators
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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
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Publications of Results:
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 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.

Other Publications:

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Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00045162    
Other Study ID Numbers: CDR0000256908
S0124 ( Other Identifier: SWOG )
S0124 ( Other Identifier: NCCTG )
S0124 ( Other Identifier: CALGB )
U10CA032102 ( U.S. NIH Grant/Contract )
First Posted: January 27, 2003    Key Record Dates
Results First Posted: July 9, 2013
Last Update Posted: July 31, 2018
Last Verified: July 2018
Keywords provided by Southwest Oncology Group:
extensive stage small cell lung cancer
Additional relevant MeSH terms:
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Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
 Irinotecan
Etoposide
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors