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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00070486
First received: October 3, 2003
Last updated: September 28, 2013
Last verified: September 2013

October 3, 2003
September 28, 2013
December 2003
December 2006   (final data collection date for primary outcome measure)
Disease free survival [ Time Frame: 9 months ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00070486 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Carboplatin and Gemcitabine Combined With Celecoxib and/or Zileuton in Treating Patients With Advanced Non-Small Cell Lung Cancer
Randomized Phase II Study of Eicosanoid Pathway Modulators and Cytotoxic Chemotherapy in Advanced Non-Small Cell Lung Cancer

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.

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.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Lung Cancer
  • Drug: carboplatin
    given IV
  • Drug: celecoxib
    given PO
  • Drug: gemcitabine hydrochloride
    given IV
  • Drug: zileuton
    given PO
  • Experimental: Gem + Carboplatin + Zileuton
    Interventions:
    • Drug: carboplatin
    • Drug: gemcitabine hydrochloride
    • Drug: zileuton
  • Experimental: Gem + Carboplatin + celecoxib
    Interventions:
    • Drug: carboplatin
    • Drug: celecoxib
    • Drug: gemcitabine hydrochloride
  • Experimental: Gem + carboplatin + zilueton + celecoxib
    Interventions:
    • Drug: carboplatin
    • Drug: celecoxib
    • Drug: gemcitabine hydrochloride
    • Drug: zileuton

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
140
May 2011
December 2006   (final data collection date for primary outcome measure)

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)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00070486
CDR0000334573, U10CA031946, CALGB-30203
No
Alliance for Clinical Trials in Oncology
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Study Chair: Martin J. Edelman, MD University of Maryland Greenebaum Cancer Center
Alliance for Clinical Trials in Oncology
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP