S0342: Paclitaxel, Carboplatin, and Cetuximab in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

Lung Cancer Clinical Trial

Official title:

Phase II Selection Design Trial Of Concurrent Chemotherapy + Cetuximab Vs. Chemotherapy Followed By Cetuximab In Advanced Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00085501
• Other study ID #: CDR0000370806
• Secondary ID: S0342U10CA032102
• Status: Completed
• Phase: Phase 2
• First received: June 10, 2004
• Last updated: October 30, 2012
• Start date: July 2004
• Est. completion date: July 2011

Study information

• Verified date: October 2012
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining more than one chemotherapy drug with a monoclonal antibody may kill more tumor cells. It is not yet known whether cetuximab is more effective when given at the same time as chemotherapy or following chemotherapy.

PURPOSE: This randomized phase II trial is studying how well giving cetuximab at the same time as combination chemotherapy works compared to giving cetuximab after combination chemotherapy in treating patients with stage IIIB or stage IV non-small cell lung cancer.

Description:

OBJECTIVES:

Primary

• Compare overall survival of patients with selected stage IIIB or stage IV non-small cell lung cancer treated with concurrent vs sequential paclitaxel, carboplatin, and cetuximab.

Secondary

• Compare response rates (confirmed and unconfirmed, complete and partial) in patients treated with these regimens.

• Compare the toxic effects of these regimens in these patients.

• Correlate epidermal growth factor receptor polymorphisms and downstream biomarkers with response to cetuximab in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I (concurrent cetuximab): Patients receive cetuximab IV over 1 hour (over 2 hours on day 1 of course 1 only) on days 1, 8, and 15 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 8. Treatment repeats every 21 days for a total of 4 courses (12 weeks) in the absence of disease progression or unacceptable toxicity. Beginning on week 13, patients receive single-agent cetuximab IV over 1 hour once weekly in the absence of disease progression or unacceptable toxicity.

• Arm II (sequential cetuximab): Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses (12 weeks) in the absence of disease progression or unacceptable toxicity. Beginning on week 13, patients receive single-agent cetuximab IV over 1 hour (over 2 hours on week 13 only) once weekly 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 180 patients (90 per treatment arm) will be accrued for this study within 9 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 242
• Est. completion date: July 2011
• Est. primary completion date: August 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) of one of the following stages:

• Newly diagnosed selected stage IIIB disease (T4 lesion due to malignant pleural effusion, any N, M0)

• Newly diagnosed stage IV disease (any T, any N, M1)

• Recurrent stage IV disease after prior surgery or radiotherapy

• The following subtypes are eligible:

• Adenocarcinoma

• Squamous cell carcinoma

• Large cell carcinoma

• Unspecified

• Measurable disease by CT scan, MRI, x-ray, or physical exam

• Pleural effusions, ascites, or laboratory parameters are not acceptable as the only evidence of disease

• Not within prior radiotherapy field unless a new lesion is present

• Not within area of prior surgical resection

• No known brain metastases by CT scan or MRI

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count = 1,500/mm^3

• Platelet count = 100,000/mm^3

• Hemoglobin = 9 mg/dL

Hepatic

• Bilirubin = 2 times upper limit of normal (ULN)

• SGOT or SGPT = 2 times ULN

• Alkaline phosphatase = 2 times ULN

• No known acute hepatitis

Renal

• Creatinine = ULN

• Creatinine clearance = 50 mL/min

Cardiovascular

• No significant cardiac disease

• No uncontrolled hypertension

• No unstable angina

• No congestive heart failure

Other

• 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 adequately treated stage I or II cancer currently in complete remission

• No active or uncontrolled infection

• No sensory neuropathy = grade 2

• No known human anti-mouse antibodies

• Not pregnant or nursing

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior biologic therapy for NSCLC

• No prior chimeric or murine monoclonal antibody therapy

• No prior cetuximab

Chemotherapy

• No prior systemic chemotherapy for NSCLC

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics

• At least 3 weeks since prior radiotherapy and recovered

Surgery

• See Disease Characteristics

• At least 2 weeks since prior thoracic or major surgery and recovered

Other

• No prior gefitinib or other investigational agents that target the epidermal growth factor receptor pathway

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

Drug:
• cetuximab
Arm 1: 400 mg/m2 (Initial dose), 2 hour IV infusion on Day 1, Week 1 only. 250 mg/m2 (Subsequent doses), 1 hour IV infusion, on Day 1 weekly starting at Week 2. Arm 2: 400 mg/m2 (Initial dose), 2 hour IV infusion on Week 13 ONLY 250 mg/m2 (Subsequent doses), 1 hour IV infusion, weekly starting at Week 14.
• carboplatin
Arm 1: AUC=6 30 minute IV infusion immediately following paclitaxel on Day 1 q 21 days x 4 starting at Week 2 Arm 2: AUC=6 30 minute IV infusion immediately following paclitaxel on Day 1 q 21 days x 4 starting at Week 1
• paclitaxel
Arm 1: 225 mg/m2 3 hour IV infusion 1 hour following cetuximab on Day 1, q 21 days x 4 Starting at Week 4. Arm 2: 225 mg/m2 3 hour IV infusion 1 hour following cetuximab on Day 1, q 21 days x 4 Starting at Week 1.

Locations

Country	Name	City	State
United States	Kapiolani Medical Center at Pali Momi	Aiea	Hawaii
United States	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio
United States	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois
United States	Alaska Regional Hospital	Anchorage	Alaska
United States	Rose Ramer Cancer Clinic at Anderson Area Medical Center	Anderson	South Carolina
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Arlington Cancer Center - Arlington	Arlington	Texas
United States	CCOP - Atlanta Regional	Atlanta	Georgia
United States	Northside Hospital Cancer Center	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia
United States	Augusta Oncology Associates	Augusta	Georgia
United States	WellStar Cobb Hospital	Austell	Georgia
United States	Cancer Care Center at Battle Creek Health System	Battle Creek	Michigan
United States	Bay Regional Medical Center	Bay City	Michigan
United States	St. Francis Hospital and Health Centers	Beech Grove	Indiana
United States	St. Joseph Hospital Community Cancer Center	Bellingham	Washington
United States	St. Charles Medical Center	Bend	Oregon
United States	Alta Bates Comprehensive Cancer Center	Berkeley	California
United States	Mecosta County General Hospital	Big Rapids	Michigan
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	St. Luke's Mountain States Tumor Institute - Boise	Boise	Idaho
United States	Cancer Research Center at Boston Medical Center	Boston	Massachusetts
United States	Olympic Hematology and Oncology	Bremerton	Washington
United States	Peninsula Medical Center	Burlingame	California
United States	St. Francis Medical Center	Cape Girardeau	Missouri
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina
United States	Tri-Health Good Samaritan Hospital	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Danville Regional Medical Center	Danville	Virginia
United States	Genesis Medical Center - West Campus	Davenport	Iowa
United States	Genesis Regional Cancer Center at Genesis Medical Center	Davenport	Iowa
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	Charles B. Eberhart Cancer Center at DeKalb Medical Center	Decatur	Georgia
United States	St. Anthony Central Hospital	Denver	Colorado
United States	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Denver	Colorado
United States	Veterans Affairs Medical Center - Denver	Denver	Colorado
United States	Josephine Ford Cancer Center at Henry Ford Health System	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	McLeod Regional Medical Center	Florence	South Carolina
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital	Gape Girardeau	Missouri
United States	Adirondack Cancer Care	Glens Falls	New York
United States	Legacy Mount Hood Medical Center	Glesham	Oregon
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	Lacks Cancer Center at Saint Mary's Mercy Medical Center	Grand Rapids	Michigan
United States	Metropolitan Hospital	Grand Rapids	Michigan
United States	Spectrum Health Cancer Care - Butterworth Campus	Grand Rapids	Michigan
United States	Spectrum Health Hospital - Blodgett Campus	Grand Rapids	Michigan
United States	Big Sky Oncology	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Sletten Regional Cancer Institute	Great Falls	Montana
United States	Marin Cancer Institute at Marin General Hospital	Greenbrae	California
United States	Sutter Health Western Division Cancer Research Group	Greenbrae	California
United States	Bon Secours St. Francis Health System	Greenville	South Carolina
United States	CCOP - Greenville	Greenville	South Carolina
United States	Greenville Hospital System Cancer Center	Greenville	South Carolina
United States	Saint Rose Hospital	Hayward	California
United States	Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Holland Community Hospital	Holland	Michigan
United States	Cancer Research Center of Hawaii	Honolula	Hawaii
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	OnCare Hawaii, Incorporated - Kuakini	Honolulu	Hawaii
United States	OnCare Hawaii, Incorporated - Lusitana	Honolulu	Hawaii
United States	Queen's Cancer Institute at Queen's Medical Center	Honolulu	Hawaii
United States	St. Francis Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital, Incorporated	Honolulu	Hawaii
United States	Community Oncology Group - Independence	Independence	Ohio
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Freeman Cancer Institute at Freeman Health System	Joplin	Missouri
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Keesler Medical Center - Keesler Air Force Base	Kessler AFB	Mississippi
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	Wilford Hall Medical Center	Lackland AFB	Texas
United States	Gwinnett Medical Center	Lawrenceville	Georgia
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Valley Memorial Hospital	Livermore	California
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	UMC Southwest Cancer and Research Center	Lubbock	Texas
United States	MedCentral - Mansfield Hospital	Mansfield	Ohio
United States	Kennestone Cancer Center at Wellstar Kennestone Hospital	Marietta	Georgia
United States	Memorial Hospital of Martinsville and Henry County	Martinsville	Virginia
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Middletown Regional Hospital	Middletown	Ohio
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
United States	Montrose Memorial Hospital Cancer Center	Montrose	Colorado
United States	Mount Clemens General Hospital	Mount Clemens	Michigan
United States	Cancer Care Center at Skagit Valley Hospital	Mt. Vernon	Washington
United States	Hackley Hospital	Muskegon	Michigan
United States	Edward Hospital Cancer Center	Naperville	Illinois
United States	Hematology Oncology Consultants Ltd.	Naperville	Illinois
United States	Tulane Cancer Center	New Orleans	Louisiana
United States	CCOP - Bay Area Tumor Institute	Oakland	California
United States	Highland General Hospital	Oakland	California
United States	Summit Medical Center	Oakland	California
United States	Comprehensive Cancer Center at Desert Regional Medical Center	Palm Springs	California
United States	Northern Michigan Hospital	Petoskey	Michigan
United States	St. Joseph Mercy Hospital	Pontiac	Michigan
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Comprehensive Cancer Center at Legacy Good Samaritan Hospital & Medical Center	Portland	Oregon
United States	Institute of Oncology at Vilnius University	Portland	Oregon
United States	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	Valley Hospital - Ridgewood	Ridgewood	New Jersey
United States	Southern Regional Medical Center	Riverdale	Georgia
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Sutter Roseville Medical Center	Roseville	California
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	Mercy General Hospital	Sacramento	California
United States	Sutter Cancer Center	Sacramento	California
United States	University of California Davis Cancer Center	Sacramento	California
United States	Seton Cancer Institute - Saginaw	Saginaw	Michigan
United States	Salem Hospital Regional Cancer Center	Salem	Oregon
United States	Salina Regional Health Center	Salina	Kansas
United States	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah
United States	California Pacific Medical Center - California Campus	San Francisco	California
United States	J.C. Robinson, M.D. Regional Cancer Center	San Pablo	California
United States	CCOP - Santa Rosa Memorial Hospital	Sana Rosa	California
United States	Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Group Health Central Hospital	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington
United States	Cancer Treatment Center at Christus Schumpert St. Mary Place	Shreveport	Louisiana
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Providence Cancer Center at Holy Family Hospital	Spokane	Washington
United States	Providence Cancer Center at Sacred Heart Medical Center	Spokane	Washington
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	St. John's Regional Health Center	Springfield	Missouri
United States	CCOP - St. Louis-Cape Girardeau	St. Louis	Missouri
United States	David C. Pratt Cancer Center at St. John's Mercy	St. Louis	Missouri
United States	Munson Medical Center	Traverse City	Michigan
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Legacy Meridian Park Hospital	Tualatin	Oregon
United States	Pearlman Comprehensive Cancer Center at South Georgia Medical Center	Valdosta	Georgia
United States	Southwest Washington Medical Center Cancer Center	Vancouver	Washington
United States	St. John Macomb Hospital	Warren	Michigan
United States	Central Washington Hospital	Wenatchee	Washington
United States	Wenatchee Valley Clinic	Wenatchee	Washington
United States	St. Anthony North Hospital	Westminster	Colorado
United States	Exempla Lutheran Medical Center	Wheat Ridge	Colorado
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Cleveland Clinic - Wooster	Wooster	Ohio
United States	United States Air Force Medical Center Wright-Patterson	Wright-Patterson Afb	Ohio
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio
United States	North Star Lodge Cancer Center	Yakima	Washington
United States	Washington Hematology - Oncology Specialists	Yakima	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (5)

Franklin WA, Gandara DR, Kim ES, et al.: SWOG S0342 and S0536: expression of EGFR protein and markers of epithelial-mesenchymal transformation (EMT) in cetuximab/chemotherapy-treated non-small cell lung cancer (NSCLC). [Abstract] J Clin Oncol 27 (Suppl 15): A-11076, 2009.

Herbst RS, Chansky K, Kelly K, et al.: A phase II randomized selection trial evaluating concurrent chemotherapy plus cetuximab or chemotherapy followed by cetuximab in patients with advanced non-small cell lung cancer (NSCLC): final report of SWOG 0342. [

Hirsch FR, Herbst RS, Olsen C, Chansky K, Crowley J, Kelly K, Franklin WA, Bunn PA Jr, Varella-Garcia M, Gandara DR. Increased EGFR gene copy number detected by fluorescent in situ hybridization predicts outcome in non-small-cell lung cancer patients trea — View Citation

Kelly K, Herbst RS, Crowley JJ, et al.: Concurrent chemotherapy plus cetuximab or chemotherapy followed by cetuximab in advanced non-small cell lung cancer (NSCLC): a randomized phase II selectional trial SWOG 0342. [Abstract] J Clin Oncol 24 (Suppl 18):

Mack PC, Holland WS, Redman M, et al.: KRAS mutation analysis in cetuximab-treated advanced stage non-small cell lung cancer (NSCLC): SWOG experience with S0342 and S0536. [Abstract] J Clin Oncol 27 (Suppl15): A-8022, 2009.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Select a regimen based on overall survival	To select a regimen based on overall survival via a Phase II selection design of chemotherapy in conjunction with cetuximab (concurrent vs. sequential) for Phase III testing against chemotherapy alone in Stage IIIB and Stage IV non-small cell lung cancer.	From date of registration until the date of progression or date of death from any cause, whichever came first, assessed up to 3 years	No
Primary	Response rate (confirmed and unconfirmed, complete and partial response)	To evaluate response rates (confirmed and unconfirmed, complete and partial) of patients with selected Stage IIIB and Stage IV NSCLC treated with paclitaxel and carboplatin with concurrent cetuximab or paclitaxel and carboplatin followed by cetuximab.	From date of registration until the date of progression or date of death from any cause, whichever came first, assessed up to 3 years	No
Primary	Toxicities	To evaluate the toxicities of the two treatment regimens in patients with selected Stage IIIB and Stage IV NSCLC.	From date of registration until the date of progression or date of death from any cause, whichever came first, assessed up to 3 years	Yes
Secondary	Correlation of epidermal growth factor receptor polymorphisms and downstream biomarkers with response	To conduct exploratory molecular correlative studies of the EGFR-HER signaling pathways examining activated phosphoproteins, oncogenic mutations and rates of proliferation and apoptosis in patient tissues (see S9925 for details).	At prestudy	No
Secondary	Evaluate EGFR polymorphisms	To evaluate EGFR polymorphisms as a potential correlate for response to cetuximab (see S9925 for details).	At prestudy and week 5	No