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Celecoxib and Erlotinib in Treating Former Smokers With Stage IIIB or Stage IV Non-Small Cell Lung Cancer
This study is ongoing, but not recruiting participants.
Sponsors and Collaborators: Duke University
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00088959
  Purpose

RATIONALE: Celecoxib and erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

PURPOSE: This phase I trial is studying the side effects and best dose of celecoxib when given together with erlotinib in treating former smokers with stage IIIB, stage IV, recurrent, or progressive non-small cell lung cancer


Condition Intervention Phase
Lung Cancer
Drug: celecoxib
Drug: erlotinib hydrochloride
Phase I

MedlinePlus related topics: Cancer Lung Cancer
Drug Information available for: Erlotinib Erlotinib hydrochloride Celecoxib 4-(5-(4-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: Phase I Study of Erlotinib and Celecoxib in Former Smokers With Advanced Non-Small Cell Lung Cancer

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Clinical toxicity and tolerability as measured by NCI CTCAE v3.0 and protocol-specific definition of dose-limiting toxicity at 4 weeks after initiation of study treatment [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Tumor response rate as measured by RECIST at 4 weeks after initiation of study treatment and periodically thereafter [ Designated as safety issue: No ]
  • Effect of study drugs on biomarkers at 4 weeks after initiation of study treatment [ Designated as safety issue: No ]

Estimated Enrollment: 45
Study Start Date: September 2004
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the clinical toxicity and tolerability of celecoxib and erlotinib hydrochloride in former smokers with stage IIIB or IV or recurrent or progressive non-small cell lung cancer.

Secondary

  • Determine the tumor response rate in patients treated with this regimen.
  • Determine the dose of celecoxib that results in maximal induction of apoptosis, maximal inhibition of prostaglandin E_2 (PGE_2) in bronchoalveolar fluid, and maximal inhibition of bronchial cell proliferation in patients treated with this regimen.

OUTLINE: This is an open-label, dose-escalation study of celecoxib.

Patients receive oral erlotinib hydrochloride once daily and oral celecoxib twice daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 6 patients receive escalating doses of celecoxib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, up to 6 additional patients are treated at the MTD.

Patients are followed at 4 weeks.

PROJECTED ACCRUAL: A total of 6-45 patients will be accrued for this study.

  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) meeting 1 of the following stage criteria:

    • Stage IIIB with pleural effusion
    • Stage IV disease
    • Recurrent or progressive disease after prior surgery, radiotherapy, and/or chemotherapy
  • Meets 1 of the following criteria:

    • Advanced NSCLC with at least stable disease after ≥ 4 courses of platinum-containing chemotherapy
    • Relapsed or refractory disease after treatment with ≥ 1 prior platinum-containing chemotherapy program, including adjuvant or neoadjuvant therapy for NSCLC

      • If the sole prior treatment was in the adjuvant or neoadjuvant setting, tumor progression or recurrence must have occurred within 6 months after completion of prior treatment
  • Former smoker, as indicated by the following:

    • At least a 30 pack-year smoking history
    • Smoking duration at least 10 years
    • At least 12 months of self-reported smoking cessation
    • Negative urine cotinine
  • No untreated brain metastases

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 10 g/dL
  • Hemostasis normal

Hepatic

  • Bilirubin ≤ 2.0 mg/dL
  • PT/PTT within 0.5 seconds of normal

Renal

  • Creatinine ≤ 2.0 mg/dL

Cardiovascular

  • No significant cardiovascular disease
  • No New York Heart Association class III or IV cardiac disease
  • No uncontrolled dysrhythmia
  • No unstable angina
  • No myocardial infarction within the past 6 months

Pulmonary

  • FEV_1 ≥ 1.0 liter OR 40% of predicted within the past 3 months
  • Oxygen saturation ≥ 90% on room air

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 6 months after study treatment
  • Willing to undergo bronchoscopy
  • No allergy to sulfonamides or hypersensitivity reaction to celecoxib
  • No other medical or psychological condition (e.g., acute psychosis) that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • See Disease Characteristics
  • At least 4 weeks since prior chemotherapy (6 weeks for mitomycin)

Endocrine therapy

  • Not specified

Radiotherapy

  • See Disease Characteristics
  • At least 4 weeks since prior radiotherapy

Surgery

  • See Disease Characteristics
  • Prior complete resection allowed provided there is histologic and cytologic documentation of disease recurrence

Other

  • More than 3 months since prior chemopreventative agents (e.g., oltipraz, retinoids, or N-acetylcysteine [NAC])
  • No prior erlotinib hydrochloride
  • No other prior EGFR antagonists
  • No concurrent medication known to interact with erlotinib hydrochloride or celecoxib, including the following:

    • Fluconazole
    • Lithium
    • Furosemide
    • Angiotensin-converting enzyme inhibitors
    • Phenytoin
    • Carbamazepine
    • Rifampin
    • Barbiturates
    • Hypericum perforatum (St. John's wort)
  • No concurrent non-steroidal anti-inflammatory drugs

    • Concurrent aspirin of up to an average dose of 325 mg/day allowed

      • No aspirin treatment for 7 days prior to any bronchoscopic or skin biopsy
  • No other concurrent EGFR inhibitors or cyclo-oxygenase-2 (COX-2) inhibitors
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00088959

Locations
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
Veterans Affairs Medical Center - Durham
Durham, North Carolina, United States, 27705
Sponsors and Collaborators
Duke University
Investigators
Principal Investigator: Michael J. Kelley, MD Duke University
  More Information

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

Study ID Numbers: CDR0000377689, DUMC-4939-04-6R2, DUMC-4939-03-6R0, VAMC-DURHAM-00813, DUMC-GCRC-911
Study First Received: August 4, 2004
Last Updated: July 23, 2008
ClinicalTrials.gov Identifier: NCT00088959  
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer

Study placed in the following topic categories:
Erlotinib
Thoracic Neoplasms
Non-small cell lung cancer
Celecoxib
Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases
Carcinoma, Non-Small-Cell Lung
Recurrence
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Analgesics, Non-Narcotic
Sensory System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 14, 2009