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

Sponsor:	Cancer and Leukemia Group B
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Cancer and Leukemia Group B
ClinicalTrials.gov Identifier:	NCT00070486

Purpose

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.

Condition	Intervention	Phase
Lung Cancer	Drug: carboplatin Drug: celecoxib Drug: gemcitabine hydrochloride Drug: zileuton	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Randomized Phase II Study of Eicosanoid Pathway Modulators and Cytotoxic Chemotherapy in Advanced Non-Small Cell Lung Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Carboplatin Gemcitabine Zileuton Gemcitabine hydrochloride Celecoxib

U.S. FDA Resources

Further study details as provided by Cancer and Leukemia Group B:

Primary Outcome Measures:

Disease free survival [ Time Frame: 9 months ] [ Designated as safety issue: No ]

Enrollment:	140
Study Start Date:	December 2003
Estimated Study Completion Date:	April 2011
Primary Completion Date:	July 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Gem + Carboplatin + Zileuton	Drug: carboplatin given IV Drug: gemcitabine hydrochloride given IV Drug: zileuton given PO
Experimental: Gem + Carboplatin + celecoxib	Drug: carboplatin given IV Drug: celecoxib given PO Drug: gemcitabine hydrochloride given IV
Experimental: Gem + carboplatin + zilueton + celecoxib	Drug: carboplatin given IV Drug: celecoxib given PO Drug: gemcitabine hydrochloride given IV Drug: zileuton given PO

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00070486

Show 75 Study Locations

Sponsors and Collaborators

Cancer and Leukemia Group B

National Cancer Institute (NCI)

Investigators

Study Chair:

Martin J. Edelman, MD

University of Maryland Greenebaum Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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.

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.

Responsible Party:	Monica M Bertagnolli, MD, Cancer and Leukemia Group B
ClinicalTrials.gov Identifier:	NCT00070486 History of Changes
Other Study ID Numbers:	CDR0000334573, U10CA031946, CALGB-30203
Study First Received:	October 3, 2003
Last Updated:	March 7, 2011
Health Authority:	United States: Federal Government

Keywords provided by Cancer and Leukemia Group B:

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

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Gemcitabine
Zileuton
Celecoxib
Carboplatin
Antimetabolites, Antineoplastic

Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics

ClinicalTrials.gov processed this record on February 09, 2012