Clinical trial NCT00085501: S0342: Paclitaxel, Carboplatin, and Cetuximab in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer
Official title: Phase II Selection Design Trial Of Concurrent Chemotherapy + Cetuximab Vs. Chemotherapy Followed By Cetuximab In Advanced Non-Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: recurrent non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
adenocarcinoma of the lung
squamous cell lung cancer
large cell lung cancer
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-06-11
Enrollment: 242
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Select a regimen based on overall survival
timeFrame: From date of registration until the date of progression or date of death from any cause, whichever came first, assessed up to 3 years
measure: Response rate (confirmed and unconfirmed, complete and partial response)
timeFrame: From date of registration until the date of progression or date of death from any cause, whichever came first, assessed up to 3 years
measure: Toxicities
timeFrame: From date of registration until the date of progression or date of death from any cause, whichever came first, assessed up to 3 years
Secondary outcomes:
measure: Correlation of epidermal growth factor receptor polymorphisms and downstream biomarkers with response
timeFrame: At prestudy
measure: Evaluate EGFR polymorphisms
timeFrame: At prestudy and week 5
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Regional Hospital
state: Alaska
city: Little Rock
country: United States
facility: Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
state: Arkansas
city: Berkeley
country: United States
facility: Alta Bates Comprehensive Cancer Center
state: California
city: Burlingame
country: United States
facility: Peninsula Medical Center
state: California
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Greenbrae
country: United States
facility: Marin Cancer Institute at Marin General Hospital
state: California
city: Greenbrae
country: United States
facility: Sutter Health Western Division Cancer Research Group
state: California
city: Hayward
country: United States
facility: Saint Rose Hospital
state: California
city: Livermore
country: United States
facility: Valley Memorial Hospital
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Oakland
country: United States
facility: Highland General Hospital
state: California
city: Oakland
country: United States
facility: CCOP - Bay Area Tumor Institute
state: California
city: Oakland
country: United States
facility: Summit Medical Center
state: California
city: Palm Springs
country: United States
facility: Comprehensive Cancer Center at Desert Regional Medical Center
state: California
city: Roseville
country: United States
facility: Sutter Roseville Medical Center
state: California
city: Sacramento
country: United States
facility: Sutter Cancer Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
city: Sacramento
country: United States
facility: Mercy General Hospital
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center - California Campus
state: California
city: San Pablo
country: United States
facility: J.C. Robinson, M.D. Regional Cancer Center
state: California
city: Sana Rosa
country: United States
facility: CCOP - Santa Rosa Memorial Hospital
state: California
city: Denver
country: United States
facility: St. Anthony Central Hospital
state: Colorado
city: Denver
country: United States
facility: University of Colorado Cancer Center at University of Colorado Health Sciences Center
state: Colorado
city: Denver
country: United States
facility: Veterans Affairs Medical Center - Denver
state: Colorado
city: Fort Collins
country: United States
facility: Poudre Valley Hospital
state: Colorado
city: Montrose
country: United States
facility: Montrose Memorial Hospital Cancer Center
state: Colorado
city: Westminster
country: United States
facility: St. Anthony North Hospital
state: Colorado
city: Wheat Ridge
country: United States
facility: Exempla Lutheran Medical Center
state: Colorado
city: Atlanta
country: United States
facility: Piedmont Hospital
state: Georgia
city: Atlanta
country: United States
facility: CCOP - Atlanta Regional
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital Cancer Center
state: Georgia
city: Atlanta
country: United States
facility: Saint Joseph's Hospital of Atlanta
state: Georgia
city: Augusta
country: United States
facility: Augusta Oncology Associates
state: Georgia
city: Austell
country: United States
facility: WellStar Cobb Hospital
state: Georgia
city: Decatur
country: United States
facility: Charles B. Eberhart Cancer Center at DeKalb Medical Center
state: Georgia
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Lawrenceville
country: United States
facility: Gwinnett Medical Center
state: Georgia
city: Marietta
country: United States
facility: Kennestone Cancer Center at Wellstar Kennestone Hospital
state: Georgia
city: Riverdale
country: United States
facility: Southern Regional Medical Center
state: Georgia
city: Savannah
country: United States
facility: Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
state: Georgia
city: Valdosta
country: United States
facility: Pearlman Comprehensive Cancer Center at South Georgia Medical Center
state: Georgia
city: Aiea
country: United States
facility: Kapiolani Medical Center at Pali Momi
state: Hawaii
city: Honolula
country: United States
facility: Cancer Research Center of Hawaii
state: Hawaii
city: Honolulu
country: United States
facility: OnCare Hawaii, Incorporated - Lusitana
state: Hawaii
city: Honolulu
country: United States
facility: Queen's Cancer Institute at Queen's Medical Center
state: Hawaii
city: Honolulu
country: United States
facility: Straub Clinic and Hospital, Incorporated
state: Hawaii
city: Honolulu
country: United States
facility: OnCare Hawaii, Incorporated - Kuakini
state: Hawaii
city: Honolulu
country: United States
facility: St. Francis Medical Center
state: Hawaii
city: Honolulu
country: United States
facility: Kapiolani Medical Center for Women and Children
state: Hawaii
city: Boise
country: United States
facility: St. Luke's Mountain States Tumor Institute - Boise
state: Idaho
city: Alton
country: United States
facility: Saint Anthony's Hospital at Saint Anthony's Health Center
state: Illinois
city: Maywood
country: United States
facility: Cardinal Bernardin Cancer Center at Loyola University Medical Center
state: Illinois
city: Naperville
country: United States
facility: Hematology Oncology Consultants Ltd.
state: Illinois
city: Naperville
country: United States
facility: Edward Hospital Cancer Center
state: Illinois
city: Beech Grove
country: United States
facility: St. Francis Hospital and Health Centers
state: Indiana
city: Davenport
country: United States
facility: Genesis Regional Cancer Center at Genesis Medical Center
state: Iowa
city: Davenport
country: United States
facility: Genesis Medical Center - West Campus
state: Iowa
city: Kansas City
country: United States
facility: Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
state: Kansas
city: Salina
country: United States
facility: Salina Regional Health Center
state: Kansas
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: New Orleans
country: United States
facility: Tulane Cancer Center
state: Louisiana
city: Shreveport
country: United States
facility: Cancer Treatment Center at Christus Schumpert St. Mary Place
state: Louisiana
city: Boston
country: United States
facility: Cancer Research Center at Boston Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: CCOP - Michigan Cancer Research Consortium
state: Michigan
city: Ann Arbor
country: United States
facility: St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Battle Creek
country: United States
facility: Cancer Care Center at Battle Creek Health System
state: Michigan
city: Bay City
country: United States
facility: Bay Regional Medical Center
state: Michigan
city: Big Rapids
country: United States
facility: Mecosta County General Hospital
state: Michigan
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Health System
state: Michigan
city: Flint
country: United States
facility: Genesys Hurley Cancer Institute
state: Michigan
city: Grand Rapids
country: United States
facility: CCOP - Grand Rapids
state: Michigan
city: Grand Rapids
country: United States
facility: Lacks Cancer Center at Saint Mary's Mercy Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Cancer Care - Butterworth Campus
state: Michigan
city: Grand Rapids
country: United States
facility: Metropolitan Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Hospital - Blodgett Campus
state: Michigan
city: Holland
country: United States
facility: Holland Community Hospital
state: Michigan
city: Mount Clemens
country: United States
facility: Mount Clemens General Hospital
state: Michigan
city: Muskegon
country: United States
facility: Hackley Hospital
state: Michigan
city: Petoskey
country: United States
facility: Northern Michigan Hospital
state: Michigan
city: Pontiac
country: United States
facility: St. Joseph Mercy Hospital
state: Michigan
city: Saginaw
country: United States
facility: Seton Cancer Institute - Saginaw
state: Michigan
city: Traverse City
country: United States
facility: Munson Medical Center
state: Michigan
city: Warren
country: United States
facility: St. John Macomb Hospital
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kessler AFB
country: United States
facility: Keesler Medical Center - Keesler Air Force Base
state: Mississippi
city: Cape Girardeau
country: United States
facility: St. Francis Medical Center
state: Missouri
city: Gape Girardeau
country: United States
facility: Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
state: Missouri
city: Joplin
country: United States
facility: Freeman Cancer Institute at Freeman Health System
state: Missouri
city: Springfield
country: United States
facility: St. John's Regional Health Center
state: Missouri
city: Springfield
country: United States
facility: Hulston Cancer Center at Cox Medical Center South
state: Missouri
city: St. Louis
country: United States
facility: CCOP - St. Louis-Cape Girardeau
state: Missouri
city: St. Louis
country: United States
facility: David C. Pratt Cancer Center at St. John's Mercy
state: Missouri
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Great Falls
country: United States
facility: Big Sky Oncology
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic
state: Montana
city: Great Falls
country: United States
facility: Sletten Regional Cancer Institute
state: Montana
city: Ridgewood
country: United States
facility: Valley Hospital - Ridgewood
state: New Jersey
city: Glens Falls
country: United States
facility: Adirondack Cancer Care
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Charlotte
country: United States
facility: Blumenthal Cancer Center at Carolinas Medical Center
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital, Incorporated
state: North Carolina
city: Hendersonville
country: United States
facility: Pardee Memorial Hospital
state: North Carolina
city: Rutherfordton
country: United States
facility: Rutherford Hospital
state: North Carolina
city: Akron
country: United States
facility: McDowell Cancer Center at Akron General Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: Tri-Health Good Samaritan Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Dayton
country: United States
facility: Grandview Hospital
state: Ohio
city: Dayton
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Dayton
country: United States
facility: David L. Rike Cancer Center at Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Samaritan North Cancer Care Center
state: Ohio
city: Dayton
country: United States
facility: Veterans Affairs Medical Center - Dayton
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Independence
country: United States
facility: Community Oncology Group - Independence
state: Ohio
city: Kettering
country: United States
facility: Charles F. Kettering Memorial Hospital
state: Ohio
city: Mansfield
country: United States
facility: MedCentral - Mansfield Hospital
state: Ohio
city: Middletown
country: United States
facility: Middletown Regional Hospital
state: Ohio
city: Troy
country: United States
facility: UVMC Cancer Care Center at Upper Valley Medical Center
state: Ohio
city: Wooster
country: United States
facility: Cleveland Clinic - Wooster
state: Ohio
city: Wright-Patterson Afb
country: United States
facility: United States Air Force Medical Center Wright-Patterson
state: Ohio
city: Xenia
country: United States
facility: Ruth G. McMillan Cancer Center at Greene Memorial Hospital
state: Ohio
city: Bend
country: United States
facility: St. Charles Medical Center
state: Oregon
city: Glesham
country: United States
facility: Legacy Mount Hood Medical Center
state: Oregon
city: Milwaukie
country: United States
facility: Providence Milwaukie Hospital
state: Oregon
city: Portland
country: United States
facility: Comprehensive Cancer Center at Legacy Good Samaritan Hospital & Medical Center
state: Oregon
city: Portland
country: United States
facility: Providence Cancer Center at Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: CCOP - Columbia River Oncology Program
state: Oregon
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Portland
country: United States
facility: Institute of Oncology at Vilnius University
state: Oregon
city: Salem
country: United States
facility: Salem Hospital Regional Cancer Center
state: Oregon
city: Tualatin
country: United States
facility: Legacy Meridian Park Hospital
state: Oregon
city: Anderson
country: United States
facility: Rose Ramer Cancer Clinic at Anderson Area Medical Center
state: South Carolina
city: Charleston
country: United States
facility: Hollings Cancer Center at Medical University of South Carolina
state: South Carolina
city: Florence
country: United States
facility: McLeod Regional Medical Center
state: South Carolina
city: Greenville
country: United States
facility: Bon Secours St. Francis Health System
state: South Carolina
city: Greenville
country: United States
facility: Greenville Hospital System Cancer Center
state: South Carolina
city: Greenville
country: United States
facility: CCOP - Greenville
state: South Carolina
city: Spartanburg
country: United States
facility: Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
state: South Carolina
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Knoxville
country: United States
facility: Thompson Cancer Survival Center
state: Tennessee
city: Arlington
country: United States
facility: Arlington Cancer Center - Arlington
state: Texas
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Lackland AFB
country: United States
facility: Wilford Hall Medical Center
state: Texas
city: Lubbock
country: United States
facility: UMC Southwest Cancer and Research Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute at University of Utah
state: Utah
city: Danville
country: United States
facility: Danville Regional Medical Center
state: Virginia
city: Martinsville
country: United States
facility: Memorial Hospital of Martinsville and Henry County
state: Virginia
city: Bellingham
country: United States
facility: St. Joseph Hospital Community Cancer Center
state: Washington
city: Bremerton
country: United States
facility: Olympic Hematology and Oncology
state: Washington
city: Mt. Vernon
country: United States
facility: Cancer Care Center at Skagit Valley Hospital
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Seattle
country: United States
facility: Group Health Central Hospital
state: Washington
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
state: Washington
city: Seattle
country: United States
facility: University Cancer Center at University of Washington Medical Center
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest - Spokane South
state: Washington
city: Spokane
country: United States
facility: Providence Cancer Center at Sacred Heart Medical Center
state: Washington
city: Spokane
country: United States
facility: Providence Cancer Center at Holy Family Hospital
state: Washington
city: Vancouver
country: United States
facility: Southwest Washington Medical Center Cancer Center
state: Washington
city: Wenatchee
country: United States
facility: Central Washington Hospital
state: Washington
city: Wenatchee
country: United States
facility: Wenatchee Valley Clinic
state: Washington
city: Yakima
country: United States
facility: North Star Lodge Cancer Center
state: Washington
city: Yakima
country: United States
facility: Washington Hematology - Oncology Specialists
state: Washington
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Roy S. Herbst, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Colorado, Denver
name: Karen Kelly, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Davis
name: David R. Gandara, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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 treated with cetuximab and chemotherapy. J Clin Oncol. 2008 Jul 10;26(20):3351-7. doi: 10.1200/JCO.2007.14.0111.
citation: 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. [Abstract] J Clin Oncol 25 (Suppl 18): A-7545, 395s, 2007.
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): A-7015, 367s, 2006.