Carboplatin and Gemcitabine Combined With Celecoxib and/or Zileuton in Treating Patients With Advanced Non-Small Cell Lung Cancer

Lung Cancer Clinical Trial

Official title:

Randomized Phase II Study of Eicosanoid Pathway Modulators and Cytotoxic Chemotherapy in Advanced Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00070486
• Other study ID #: CALGB-30203
• Secondary ID: U10CA031946CALGB
• Status: Completed
• Phase: Phase 2
• First received: October 3, 2003
• Last updated: June 28, 2016
• Start date: December 2003
• Est. completion date: May 2011

Study information

• Verified date: June 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: May 2011
• Est. primary completion date: December 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 120 Years

Eligibility

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)

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:
• carboplatin
given IV
• celecoxib
given PO
• gemcitabine hydrochloride
given IV
• zileuton
given PO

Locations

Country	Name	City	State
United States	Northeast Alabama Regional Medical Center	Anniston	Alabama
United States	Veterans Affairs Medical Center - Asheville	Asheville	North Carolina
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Veterans Affairs Medical Center - Buffalo	Buffalo	New York
United States	Vermont Cancer Center at University of Vermont	Burlington	Vermont
United States	Cooper University Hospital	Camden	New Jersey
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	Martha Jefferson Hospital	Charlottesville	Virginia
United States	Louis A. Weiss Memorial Hospital	Chicago	Illinois
United States	MBCCOP - University of Illinois at Chicago	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Veterans Affairs Medical Center - Chicago (Westside Hospital)	Chicago	Illinois
United States	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri
United States	Veterans Affairs Medical Center - Columbia (Truman Memorial)	Columbia	Missouri
United States	Arthur G. James Cancer Hospital at Ohio State University	Columbus	Ohio
United States	NorthEast Oncology Associates - Concord	Concord	North Carolina
United States	Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Veterans Affairs Medical Center - Dallas	Dallas	Texas
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Veterans Affairs Medical Center - Durham	Durham	North Carolina
United States	CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.	East Syracuse	New York
United States	CCOP - Evanston	Evanston	Illinois
United States	Cape Fear Valley Health System	Fayetteville	North Carolina
United States	Broward General Medical Center	Fort Lauderdale	Florida
United States	Fort Wayne Medical Oncology and Hematology, Incorporated	Fort Wayne	Indiana
United States	CCOP - Southeast Cancer Control Consortium	Goldsboro	North Carolina
United States	Memorial Regional Cancer Center at Memorial Regional Hospital	Hollywood	Florida
United States	New Hampshire Oncology-Hematology, PA - Hooksett	Hooksett	New Hampshire
United States	St. Mary's Medical Center	Huntington	West Virginia
United States	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa
United States	Queens Cancer Center of Queens Hospital	Jamaica	New York
United States	CCOP - Kansas City	Kansas City	Missouri
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Veterans Affairs Medical Center - Las Vegas	Las Vegas	Nevada
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center	Los Angeles	California
United States	Baptist Hospital East - Louisville	Louisville	Kentucky
United States	CCOP - North Shore University Hospital	Manhasset	New York
United States	North Shore University Hospital	Manhasset	New York
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Veterans Affairs Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	New York Weill Cornell Cancer Center at Cornell University	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Virginia Oncology Associates - Norfolk	Norfolk	Virginia
United States	Oklahoma University Medical Center	Oklahoma City	Oklahoma
United States	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	FirstHealth Moore Regional Hospital	Pinehurst	North Carolina
United States	Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	Lifespan: The Miriam Hospital	Providence	Rhode Island
United States	MBCCOP - Massey Cancer Center	Richmond	Virginia
United States	West Suburban Center for Cancer Care	River Forest	Illinois
United States	Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke	Roanoke	Virginia
United States	Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph	Saint Joseph	Michigan
United States	Missouri Baptist Cancer Center	Saint Louis	Missouri
United States	Siteman Cancer Center	Saint Louis	Missouri
United States	Naval Medical Center - San Diego	San Diego	California
United States	Veterans Affairs Medical Center - San Diego	San Diego	California
United States	UCSF Comprehensive Cancer Center	San Francisco	California
United States	Veterans Affairs Medical Center - San Francisco	San Francisco	California
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	University Hospital at State University of New York - Upstate Medical University	Syracuse	New York
United States	Veterans Affairs Medical Center - Syracuse	Syracuse	New York
United States	Lombardi Cancer Center at Georgetown University Medical Center	Washington	District of Columbia
United States	Veterans Affairs Medical Center - Washington, DC	Washington	District of Columbia
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	Palm Beach Cancer Institute	West Palm Beach	Florida
United States	Zimmer Cancer Center at New Hanover Regional Medical Center	Wilmington	North Carolina
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina
United States	University of Massachusetts Memorial Medical Center - University Campus	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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 — View 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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease free survival		9 months	No