Clinical trial NCT00103207: Cetuximab in Treating Patients With Recurrent or Stage IIIB or Stage IV Lung Cancer
Official title: Phase II Study of C225 (Cetuximab) for the Treatment of Patients With Advanced Bronchioalveolar Carcinoma (BAC) or Adenocarcinoma With BAC Features
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: bronchioalveolar carcinoma (BAC)
adenocarcinoma with BAC features
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
recurrent non-small cell lung cancer
cetuximab
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-02-08
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.

PURPOSE: This phase II trial is studying how well cetuximab works in treating patients with recurrent or stage IIIB or stage IV lung cancer.

Detailed description: OBJECTIVES:

Primary

* Determine the objective response rate in patients with recurrent or stage IIIB or IV bronchoalveolar carcinoma (BAC) or adenocarcinoma of the lung with BAC features treated with cetuximab.

Secondary

* Determine the overall survival and time to progression in patients treated with this drug.
* Determine the toxic effects of this drug in these patients.
* Correlate expression of total and phosphorylated epidermal growth factor receptor (EGFR), total and phosphorylated AKT3, and total and phosphorylated MAPKinase with response in patients treated with this drug.
* Determine whether the presence of polymorphisms or mutations in the EGFR gene influences response in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive cetuximab IV over 1-2 hours once on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

ACTUAL ACCRUAL: A total of 72 patients were accrued for this study.

Eligibility criteria: INCLUSION CRITERIA:

* Histologically or cytologically confirmed bronchoalveolar carcinoma (BAC) or adenocarcinoma of the lung with BAC features meeting 1 of the following stage criteria:

  * Stage IIIB disease (with pleural or pericardial effusion)
  * Stage IV disease
  * Recurrent disease
* Measurable disease
* Tumor tissue available from biopsy
* Age of 18 and over
* ECOG performance status of 0-2
* Life expectancy greater than 3 months
* White blood cell (WBC) ≥ 3,000/mm\^3
* Absolute neutrophil count ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Bilirubin normal
* Aspartate aminotransferase (AST) and/or alanine aminotranferease (ALT) ≤ 2.5 times upper limit of normal
* Creatinine normal OR Creatinine clearance ≥ 60 mL/min
* No more than 1 prior chemotherapy regimen for advanced BAC
* More than 3 years since prior chemotherapy for other malignancies
* At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) for this malignancy and recovered
* HIV-positive patients are eligible provided the following criteria are met:

  * CD4 count ≥ 100/mm\^3
  * Undetectable viral load within the past 3 months
  * Receiving a stable antiretroviral regimen for ≥ 4 weeks before study entry
* Fertile patients must use effective contraception
* At least 2 weeks since prior radiotherapy and recovered

EXCLUSION CRITERIA:

* Untreated brain metastases

  * Patients with stable brain metastases ≥ 4 weeks after external beam radiotherapy to the brain are eligible
* Acute hepatitis
* Symptomatic congestive heart failure
* Uncontrolled hypertension
* Unstable angina pectoris
* Cardiac arrhythmia
* Pregnant or nursing
* Prior allergic reaction to chimerized or murine monoclonal antibody therapy
* Documented presence of human anti-mouse antibodies
* Ongoing or active infection
* Psychiatric illness or social situation that would preclude study compliance
* Other uncontrolled illness
* Prior cetuximab
* Concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)
* Other prior known epidermal growth factor receptor inhibitors (e.g., gefitinib or erlotinib)
* Other concurrent investigational agents
* Other concurrent anticancer therapy

Primary outcomes:
measure: Objective Response Rate (Proportion of Patients With Objective Response)
timeFrame: Assessed every 8 weeks during treatment; after off-treatment, every 3 months for 2 years and then every 6 months for 3 years
Secondary outcomes:
measure: Overall Survival
timeFrame: Every week during treatment; after off-treatment, every 3 months for 2 years and then every 6 months for 3 years
measure: Time to Progression
timeFrame: Assessed every 8 weeks during treatment; after off-treatment, every 3 months for 2 years and then every 6 months for 3 years
measure: Overall Survival by Smoking Status
timeFrame: Overall survival assessed every week during treatment; after off-treatment, every 3 months for 2 years and then every 6 months for 3 years. Smoking status evaluated at baseline
measure: Time to Progression by Smoking Status
timeFrame: Progression assessed every 8 weeks during treatment; after off-treatment, every 3 months for 2 years and then every 6 months for 3 years. Smoking status evaluated at baseline
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Aurora Presbyterian Hospital
state: Colorado
city: Colorado Springs
country: United States
facility: Penrose Cancer Center at Penrose Hospital
state: Colorado
city: Denver
country: United States
facility: St. Anthony Central Hospital
state: Colorado
city: Denver
country: United States
facility: Porter Adventist Hospital
state: Colorado
city: Denver
country: United States
facility: Presbyterian - St. Luke's Medical Center
state: Colorado
city: Denver
country: United States
facility: St. Joseph Hospital
state: Colorado
city: Denver
country: United States
facility: Rose Medical Center
state: Colorado
city: Denver
country: United States
facility: CCOP - Colorado Cancer Research Program
state: Colorado
city: Englewood
country: United States
facility: Swedish Medical Center
state: Colorado
city: Grand Junction
country: United States
facility: St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
state: Colorado
city: Greeley
country: United States
facility: North Colorado Medical Center
state: Colorado
city: Lone Tree
country: United States
facility: Sky Ridge Medical Center
state: Colorado
city: Longmont
country: United States
facility: Hope Cancer Care Center at Longmont United Hospital
state: Colorado
city: Loveland
country: United States
facility: McKee Medical Center
state: Colorado
city: Pueblo
country: United States
facility: St. Mary - Corwin Regional Medical Center
state: Colorado
city: Thornton
country: United States
facility: North Suburban Medical Center
state: Colorado
city: Wheat Ridge
country: United States
facility: Exempla Lutheran Medical Center
state: Colorado
city: Boca Raton
country: United States
facility: Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus
state: Florida
city: Jacksonville
country: United States
facility: Baptist Cancer Institute - Jacksonville
state: Florida
city: Aurora
country: United States
facility: Rush-Copley Cancer Care Center
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital Cancer Care Institute
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates, Limited - West
state: Illinois
city: Rockford
country: United States
facility: Swedish-American Regional Cancer Center
state: Illinois
city: Springfield
country: United States
facility: Regional Cancer Center at Memorial Medical Center
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center at Carle Foundation Hospital
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Michigan City
country: United States
facility: Saint Anthony Memorial Health Centers
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic, PC
state: Iowa
city: Cedar Rapids
country: United States
facility: Cedar Rapids Oncology Associates
state: Iowa
city: Des Moines
country: United States
facility: Mercy Capitol Hospital
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at John Stoddard Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at Mercy Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Mercy Cancer Center at Mercy Medical Center - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Lutheran Hospital
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates, LLP
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center - Sioux City
state: Iowa
city: Sioux City
country: United States
facility: St. Luke's Regional Medical Center
state: Iowa
city: Chanute
country: United States
facility: Cancer Center of Kansas, PA - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas, PA - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas, PA - El Dorado
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas, PA - Kingman
state: Kansas
city: Liberal
country: United States
facility: Southwest Medical Center
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas, PA - Newton
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas, PA - Parsons
state: Kansas
city: Pratt
country: United States
facility: Cancer Center of Kansas, PA - Pratt
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas, PA - Salina
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas, PA - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates in Womens Health, PA - North Review
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Wichita
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas, PA - Winfield
state: Kansas
city: Taunton
country: United States
facility: Morton Hospital & Medical Center
state: Massachusetts
city: Adrian
country: United States
facility: Hickman Cancer Center at Bixby Medical Center
state: Michigan
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Cancer Center
state: Michigan
city: Ann Arbor
country: United States
facility: CCOP - Michigan Cancer Research Consortium
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Cancer Center at Oakwood Hospital and Medical Center
state: Michigan
city: Flint
country: United States
facility: Genesys Hurley Cancer Institute
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: Van Elslander Cancer Center at St. John Hospital and Medical Center
state: Michigan
city: Jackson
country: United States
facility: Foote Memorial Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: Borgess Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Lambertville
country: United States
facility: Haematology-Oncology Associates of Ohio and Michigan, PC
state: Michigan
city: Lansing
country: United States
facility: Sparrow Regional Cancer Center
state: Michigan
city: Livonia
country: United States
facility: St. Mary Mercy Hospital
state: Michigan
city: Monroe
country: United States
facility: Community Cancer Center of Monroe
state: Michigan
city: Monroe
country: United States
facility: Mercy Memorial Hospital - Monroe
state: Michigan
city: Pontiac
country: United States
facility: St. Joseph Mercy Oakland
state: Michigan
city: Port Huron
country: United States
facility: Mercy Regional Cancer Center at Mercy Hospital
state: Michigan
city: Saginaw
country: United States
facility: Seton Cancer Institute at Saint Mary's - Saginaw
state: Michigan
city: Warren
country: United States
facility: St. John Macomb Hospital
state: Michigan
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Coon Rapids
country: United States
facility: Mercy and Unity Cancer Center at Mercy Hospital
state: Minnesota
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Fridley
country: United States
facility: Mercy and Unity Cancer Center at Unity Hospital
state: Minnesota
city: Hutchinson
country: United States
facility: Hutchinson Area Health Care
state: Minnesota
city: Litchfield
country: United States
facility: Meeker County Memorial Hospital
state: Minnesota
city: Maplewood
country: United States
facility: HealthEast Cancer Care at St. John's Hospital
state: Minnesota
city: Maplewood
country: United States
facility: Minnesota Oncology Hematology, PA - Maplewood
state: Minnesota
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin County Medical Center - Minneapolis
state: Minnesota
city: Robbinsdale
country: United States
facility: Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Saint Louis Park
country: United States
facility: Park Nicollet Cancer Center
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital Cancer Care Center
state: Minnesota
city: Saint Paul
country: United States
facility: HealthEast Cancer Care at St. Joseph's Hospital
state: Minnesota
city: Saint Paul
country: United States
facility: United Hospital
state: Minnesota
city: Shakopee
country: United States
facility: St. Francis Cancer Center at St. Francis Medical Center
state: Minnesota
city: Waconia
country: United States
facility: Ridgeview Medical Center
state: Minnesota
city: Woodbury
country: United States
facility: HealthEast Cancer Care at Woodwinds Health Campus
state: Minnesota
city: Woodbury
country: United States
facility: Minnesota Oncology Hematology, PA - Woodbury
state: Minnesota
city: East Orange
country: United States
facility: Veterans Affairs Medical Center - East Orange
state: New Jersey
city: Flemington
country: United States
facility: Hunterdon Regional Cancer Center at Hunterdon Medical Center
state: New Jersey
city: Marlton
country: United States
facility: Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
state: New Jersey
city: Red Bank
country: United States
facility: Booker Cancer Center at Riverview Medical Center
state: New Jersey
city: Voorhees
country: United States
facility: Fox Chase Virtua Health Cancer Program at Virtua West Jersey
state: New Jersey
city: Akron
country: United States
facility: Summa Center for Cancer Care at Akron City Hospital
state: Ohio
city: Bowling Green
country: United States
facility: Wood County Oncology Center
state: Ohio
city: Canton
country: United States
facility: Aultman Cancer Center at Aultman Hospital
state: Ohio
city: Elyria
country: United States
facility: Hematology Oncology Center
state: Ohio
city: Lima
country: United States
facility: St. Rita's Medical Center
state: Ohio
city: Lima
country: United States
facility: Lima Memorial Hospital
state: Ohio
city: Maumee
country: United States
facility: Northwest Ohio Oncology Center
state: Ohio
city: Maumee
country: United States
facility: St. Luke's Hospital
state: Ohio
city: Oregon
country: United States
facility: St. Charles Mercy Hospital
state: Ohio
city: Oregon
country: United States
facility: Toledo Clinic - Oregon
state: Ohio
city: Sandusky
country: United States
facility: North Coast Cancer Care, Incorporated
state: Ohio
city: Sylvania
country: United States
facility: Flower Hospital Cancer Center
state: Ohio
city: Tiffin
country: United States
facility: Mercy Hospital of Tiffin
state: Ohio
city: Toledo
country: United States
facility: Toledo Hospital
state: Ohio
city: Toledo
country: United States
facility: St. Vincent Mercy Medical Center
state: Ohio
city: Toledo
country: United States
facility: Medical University of Ohio Cancer Center
state: Ohio
city: Toledo
country: United States
facility: CCOP - Toledo Community Hospital
state: Ohio
city: Toledo
country: United States
facility: Toledo Clinic, Incorporated - Main Clinic
state: Ohio
city: Wauseon
country: United States
facility: Fulton County Health Center
state: Ohio
city: Bethlehem
country: United States
facility: St. Luke's Cancer Network at St. Luke's Hospital
state: Pennsylvania
city: Bryn Mawr
country: United States
facility: Bryn Mawr Hospital
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Cancer Institute at Geisinger Health
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Lewistown
country: United States
facility: Lewistown Hospital
state: Pennsylvania
city: Paoli
country: United States
facility: Cancer Center of Paoli Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Centers
state: Pennsylvania
city: Reading
country: United States
facility: St. Joseph Medical Center
state: Pennsylvania
city: Reading
country: United States
facility: McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
state: Pennsylvania
city: Scranton
country: United States
facility: Mercy Hospital Cancer Center - Scranton
state: Pennsylvania
city: Scranton
country: United States
facility: Hematology and Oncology Associates of Northeastern Pennsylvania
state: Pennsylvania
city: State College
country: United States
facility: Geisinger Medical Group - Scenery Park
state: Pennsylvania
city: State College
country: United States
facility: Mount Nittany Medical Center
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
state: Pennsylvania
city: Wynnewood
country: United States
facility: CCOP - Main Line Health
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Cancer Center at Lankenau Hospital
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Sioux Falls
country: United States
facility: Medical X-Ray Center, PC
state: South Dakota
city: Sioux Falls
country: United States
facility: Sanford Cancer Center at Sanford USD Medical Center
state: South Dakota
city: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: Fredericksburg
country: United States
facility: Fredericksburg Oncology, Incorporated
state: Virginia
city: Eau Claire
country: United States
facility: Center for Cancer Treatment & Prevention at Sacred Heart Hospital
state: Wisconsin
city: Eau Claire
country: United States
facility: Marshfield Clinic Cancer Care at Regional Cancer Center
state: Wisconsin
city: La Crosse
country: United States
facility: Gundersen Lutheran Center for Cancer and Blood
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Clinic - Marshfield Center
state: Wisconsin
city: Marshfield
country: United States
facility: Saint Joseph's Hospital
state: Wisconsin
city: Minocqua
country: United States
facility: Marshfield Clinic - Lakeland Center
state: Wisconsin
city: Rhinelander
country: United States
facility: Ministry Medical Group at Saint Mary's Hospital
state: Wisconsin
city: Rice Lake
country: United States
facility: Marshfield Clinic - Indianhead Center
state: Wisconsin
city: Stevens Point
country: United States
facility: Saint Michael's Hospital Cancer Center
state: Wisconsin
city: Wausau
country: United States
facility: Marshfield Clinic - Wausau Center
state: Wisconsin
city: Wausau
country: United States
facility: University of Wisconcin Cancer Center at Aspirus Wausau Hospital
state: Wisconsin
city: Wisconsin Rapids
country: United States
facility: Marshfield Clinic - Wisconsin Rapids Center
state: Wisconsin
Study officials:
affiliation: Emory Winship Cancer Institute
name: Suresh Ramalingam, MD
role: STUDY_CHAIR
References:
citation: Ramalingam SS, Lee JW, Belani CP, Aisner SC, Kolesar J, Howe C, Velasco MR, Schiller JH. Cetuximab for the treatment of advanced bronchioloalveolar carcinoma (BAC): an Eastern Cooperative Oncology Group phase II study (ECOG 1504). J Clin Oncol. 2011 May 1;29(13):1709-14. doi: 10.1200/JCO.2010.33.4094. Epub 2011 Mar 21.