Clinical trial NCT00070486: Carboplatin and Gemcitabine Combined With Celecoxib and/or Zileuton in Treating Patients With Advanced Non-Small Cell Lung Cancer
Official title: Randomized Phase II Study of Eicosanoid Pathway Modulators and Cytotoxic Chemotherapy in Advanced Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: stage IV non-small cell lung cancer
adenocarcinoma of the lung
squamous cell lung cancer
large cell lung cancer
stage IIIB non-small cell lung cancer
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-10-07
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
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 carboplatin and gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Celecoxib and zileuton may stop the growth of tumor cells by stopping blood flow to the tumor and may block the enzymes necessary for tumor cell growth. Combining chemotherapy with celecoxib and/or zileuton may kill more tumor cells.

PURPOSE: Randomized phase II trial to study the effectiveness of combining celecoxib and/or zileuton with carboplatin and gemcitabine in treating patients who have advanced non-small cell lung cancer.

Detailed description: OBJECTIVES:

Primary

* Compare the efficacy of carboplatin and gemcitabine with celecoxib and/or zileuton, in terms of 7-month progression-free survival, in patients with advanced non-small cell lung cancer.

Secondary

* Compare the response rate, distribution of survival, and failure-free survival time of patients treated with these regimens.
* Correlate CYFRA and serum vascular endothelial growth factor levels with response and survival of patients treated with these regimens.
* Correlate cyclo-oxygenase-2 and 5-lipoxygenase expression with survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 3 treatment arms.

* Arm I: Patients receive gemcitabine IV over 30 minutes on days 1 and 8, carboplatin IV over 30 minutes on day 1, and oral zileuton 4 times daily on days 1-21.
* Arm II: Patients receive gemcitabine and carboplatin as in arm I and oral celecoxib twice daily on days 1-21.
* Arm III: Patients receive gemcitabine and carboplatin as in arm I, oral celecoxib as in arm II, and oral zileuton as in arm I.

In all arms, treatment repeats every 21 days for 6 courses. Patients with responding or stable disease continue courses of zileuton and/or celecoxib in the absence of disease progression or unacceptable toxicity.

Patients are followed monthly for 1 year, every 2 months for 2 years, and then every 4 months for 3 years or until disease progression.

PROJECTED ACCRUAL: A total of 117 patients (39 per treatment arm) will be accrued for this study within 11-12 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) of 1 of the following cellular types:

  * Adenocarcinoma
  * Large cell
  * Squamous cell
  * Mixed
* Meets 1 of the following staging criteria:

  * Stage IIIB disease with malignant pleural effusion, supraclavicular node involvement, or contralateral hilar nodes

    * Stage IIIB patients eligible for Cancer and Leukemia Group B protocols of combined chemotherapy and chest irradiation are not allowed
  * Stage IV disease
* Measurable or nonmeasurable disease

  * Unidimensionally measurable lesions at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
  * The following are considered nonmeasurable disease:

    * Bone lesions
    * Ascites
    * Pleural/pericardial effusion
    * Lymphangitis cutis/pulmonis
    * Abdominal masses that are not confirmed and followed by imaging techniques
    * Cystic lesions
    * Small lesions
* No leptomeningeal disease
* Symptomatic CNS metastases must be treated (e.g., surgery, radiotherapy, or gamma knife), neurologically stable, and off steroids

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* ECOG 0-2

Life expectancy

* Not specified

Hematopoietic

* Granulocyte count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic

* Bilirubin no greater than 1.5 mg/dL
* AST no greater than 2.0 times upper limit of normal

Renal

* Creatinine no greater than 1.5 mg/dL

Cardiovascular

* None of the following within the past 6 months:

  * Myocardial infarction
  * Unstable angina
  * Symptomatic congestive heart failure
  * Serious uncontrolled cardiac arrhythmia
  * Cerebrovascular accident
  * Transient ischemic attack
  * Symptomatic carotid artery or peripheral vascular disease
  * Deep vein thrombosis
  * Significant thromboembolic event

Pulmonary

* No pulmonary embolism within the past 6 months

Gastrointestinal

* No history of gastrointestinal (GI) bleeding
* No history of peptic ulcer disease
* No active GI bleeding

Other

* Not pregnant or nursing
* No known hypersensitivity to aspirin, NSAIDs, or sulfonamides
* No currently active second malignancy other than nonmelanoma skin cancer

  * Patients are not considered to have a currently active malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No prior immunotherapy for NSCLC

Chemotherapy

* No prior chemotherapy for NSCLC
* No other concurrent chemotherapy

Endocrine therapy

* See Disease Characteristics
* No concurrent chronic oral steroids

  * Concurrent episodic steroids for antiemetic purposes allowed
* No concurrent hormonal therapy
* Concurrent inhaled steroids allowed when medically indicated
* Concurrent megestrol for appetite stimulation is allowed

Radiotherapy

* See Disease Characteristics
* At least 2 weeks since prior radiotherapy and recovered

Surgery

* See Disease Characteristics
* At least 2 weeks since prior surgery and recovered

Other

* No prior systemic treatments for NSCLC
* No other concurrent investigational therapy
* At least 1 week since prior nonsteroidal anti-inflammatory drugs (NSAIDs), including any of the following:

  * Rofecoxib
  * Choline magnesium trisalicylate
  * Ibuprofen
  * Naproxen
  * Etodolac
  * Oxaprozin
  * Diflunisal
  * Nabumetone
  * Tolmetin
  * Valdecoxib
* No concurrent NSAIDs
* No concurrent chronic aspirin

  * Concurrent aspirin no greater than 325 mg/day is allowed
* No concurrent fluconazole
* No concurrent leukotriene antagonists (e.g., zafirlukast, montelukast, or pranlukast)

Primary outcomes:
measure: Disease free survival
timeFrame: 9 months
Secondary outcomes:
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Northeast Alabama Regional Medical Center
state: Alabama
city: La Jolla
country: United States
facility: Rebecca and John Moores UCSD Cancer Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center
state: California
city: San Diego
country: United States
facility: Naval Medical Center - San Diego
state: California
city: San Diego
country: United States
facility: Veterans Affairs Medical Center - San Diego
state: California
city: San Francisco
country: United States
facility: UCSF Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: Veterans Affairs Medical Center - San Francisco
state: California
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Washington
country: United States
facility: Lombardi Cancer Center at Georgetown University Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Veterans Affairs Medical Center - Washington, DC
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Broward General Medical Center
state: Florida
city: Hollywood
country: United States
facility: Memorial Regional Cancer Center at Memorial Regional Hospital
state: Florida
city: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Cancer Institute
state: Florida
city: Chicago
country: United States
facility: MBCCOP - University of Illinois at Chicago
state: Illinois
city: Chicago
country: United States
facility: Veterans Affairs Medical Center - Chicago (Westside Hospital)
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Chicago
country: United States
facility: Louis A. Weiss Memorial Hospital
state: Illinois
city: Evanston
country: United States
facility: CCOP - Evanston
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: River Forest
country: United States
facility: West Suburban Center for Cancer Care
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Incorporated
state: Indiana
city: South Bend
country: United States
facility: CCOP - Northern Indiana CR Consortium
state: Indiana
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
city: Louisville
country: United States
facility: Baptist Hospital East - Louisville
state: Kentucky
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center - University Campus
state: Massachusetts
city: Saint Joseph
country: United States
facility: Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph
state: Michigan
city: Minneapolis
country: United States
facility: Veterans Affairs Medical Center - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Columbia
country: United States
facility: Veterans Affairs Medical Center - Columbia (Truman Memorial)
state: Missouri
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center at University of Missouri - Columbia
state: Missouri
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center
state: Missouri
city: Saint Louis
country: United States
facility: Missouri Baptist Cancer Center
state: Missouri
city: Omaha
country: United States
facility: UNMC Eppley Cancer Center at the University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: CCOP - Southern Nevada Cancer Research Foundation
state: Nevada
city: Las Vegas
country: United States
facility: Veterans Affairs Medical Center - Las Vegas
state: Nevada
city: Hooksett
country: United States
facility: New Hampshire Oncology-Hematology, PA - Hooksett
state: New Hampshire
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Buffalo
country: United States
facility: Veterans Affairs Medical Center - Buffalo
state: New York
city: East Syracuse
country: United States
facility: CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
state: New York
city: Jamaica
country: United States
facility: Queens Cancer Center of Queens Hospital
state: New York
city: Manhasset
country: United States
facility: CCOP - North Shore University Hospital
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: New York Weill Cornell Cancer Center at Cornell University
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Syracuse
country: United States
facility: University Hospital at State University of New York - Upstate Medical University
state: New York
city: Syracuse
country: United States
facility: Veterans Affairs Medical Center - Syracuse
state: New York
city: Asheville
country: United States
facility: Veterans Affairs Medical Center - Asheville
state: North Carolina
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
city: Concord
country: United States
facility: NorthEast Oncology Associates - Concord
state: North Carolina
city: Durham
country: United States
facility: Veterans Affairs Medical Center - Durham
state: North Carolina
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Fayetteville
country: United States
facility: Cape Fear Valley Health System
state: North Carolina
city: Goldsboro
country: United States
facility: CCOP - Southeast Cancer Control Consortium
state: North Carolina
city: Pinehurst
country: United States
facility: FirstHealth Moore Regional Hospital
state: North Carolina
city: Wilmington
country: United States
facility: Zimmer Cancer Center at New Hanover Regional Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center at Wake Forest University
state: North Carolina
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital at Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Medical Center
state: Oklahoma
city: Pittsburgh
country: United States
facility: Western Pennsylvania Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Lifespan: The Miriam Hospital
state: Rhode Island
city: Dallas
country: United States
facility: Veterans Affairs Medical Center - Dallas
state: Texas
city: Dallas
country: United States
facility: Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
city: Burlington
country: United States
facility: Vermont Cancer Center at University of Vermont
state: Vermont
city: Charlottesville
country: United States
facility: Martha Jefferson Hospital
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates - Norfolk
state: Virginia
city: Richmond
country: United States
facility: MBCCOP - Massey Cancer Center
state: Virginia
city: Roanoke
country: United States
facility: Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke
state: Virginia
city: Huntington
country: United States
facility: St. Mary's Medical Center
state: West Virginia
Study officials:
affiliation: University of Maryland Greenbaum Cancer Center
name: Martin Edelman, MD
role: STUDY_CHAIR
References:
citation: Edelman MJ, Watson D, Wang X, Morrison C, Kratzke RA, Jewell S, Hodgson L, Mauer AM, Gajra A, Masters GA, Bedor M, Vokes EE, Green MJ. Eicosanoid modulation in advanced lung cancer: cyclooxygenase-2 expression is a positive predictive factor for celecoxib + chemotherapy--Cancer and Leukemia Group B Trial 30203. J Clin Oncol. 2008 Feb 20;26(6):848-55. doi: 10.1200/JCO.2007.13.8081.
citation: Edelman, MJ, Watson DM, Wang X, et al.: Eicosanoid modulation in advanced non-small cell lung cancer (NSCLC): CALGB 30203. [Abstract] J Clin Oncol 24 (Suppl 18): A-7025, 370s, 2006.