Celecoxib and Erlotinib in Treating Former Smokers With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

This study has been completed.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
First received: August 4, 2004
Last updated: October 9, 2014
Last verified: April 2013
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. Celecoxib and erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

Condition Intervention Phase
Recurrent Non-small Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Drug: erlotinib hydrochloride
Drug: celecoxib
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Erlotinib and Celecoxib in Former Smokers With Advanced Non-Small Cell Lung Cancer

Resource links provided by NLM:

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

Primary Outcome Measures:
  • Clinical tolerable dose of celecoxib as measured by NCI CTCAE v3.0 [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 45
Study Start Date: December 2003
Study Completion Date: November 2010
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (erlotinib hydrochloride, celecoxib)
Patients receive oral erlotinib hydrochloride once daily and oral celecoxib twice daily. Treatment continues in the absence of disease progression or unacceptable toxicity.
Drug: erlotinib hydrochloride
Given orally
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Drug: celecoxib
Given orally
Other Names:
  • Celebrex
  • SC-58635
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:


I. To estimate the clinical toxicity and tolerability of erlotinib combined with celecoxib in patients with advanced non-small cell lung cancer (NSCLC).


I. To estimate the tumor response rate of erlotinib combined with celecoxib in patients with advanced NSCLC.

II. To estimate the dose of celecoxib that results in maximal induction of apoptosis, maximal inhibition of prostaglandin E2 (PGE2) in bronchoalveolar (BAL) fluid, and maximal inhibition of bronchial cell proliferation when combined with erlotinib.

III. To estimate the effect of erlotinib and the combination of erlotinib and celecoxib on bronchial expression of COX-2.

IV. To estimate the effect of erlotinib and the combination of erlotinib (and celecoxib on autophosphorylation of epidermal growth factor receptor (EGFR) in skin and endobronchial biopsies.

V. To estimate the degree of correlation of autophosphorylation of EGFR in skin and endobronchial samples.


I. To estimate the effect of the combination of erlotinib and COX-2 inhibitor (celecoxib) on the frequency of fractional allelic loss (FAL) in endobronchial biopsies, metaplasia and dysplasia in endobronchial biopsies, and endobronchial proliferation.

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.


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


  • 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
  • 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
  • Absolute neutrophil count >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Hemoglobin >= 10 g/dL
  • Hemostasis normal
  • Creatinine =< 2.0 mg/dL
  • 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
  • FEV1 >= 1.0 liter OR 40% of predicted within the past 3 months
  • Oxygen saturation >= 90% on room air
  • 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
  • At least 4 weeks since prior chemotherapy (6 weeks for mitomycin)
  • At least 4 weeks since prior radiotherapy
  • Prior complete resection allowed provided there is histologic and cytologic documentation of disease recurrence
  • 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
  • Meets 1 of the following criteria: 1) Advanced NSCLC with at least stable disease after >= 4 courses of platinum-containing chemotherapy 2) Relapsed or refractory disease after treatment with >= 1 prior platinum-containing chemotherapy program, including adjuvant or neoadjuvant therapy for NSCLC
  • No untreated brain metastases
  • ECOG 0-1
  • Former smoker, as indicated by the following: 1) At least a 30 pack-year smoking history 2) Smoking duration at least 10 years 3) At least 12 months of self-reported smoking cessation 4) Negative urine cotinine
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00088959

United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Michael Kelley Duke University
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00088959     History of Changes
Other Study ID Numbers: NCI-2009-00886  4939-04-6R2  DUMC-4939-03-6R0  VAMC-DURHAM-00813  DUMC-GCRC-911  CDR0000377689  DUMC-4939-04-6R2  U01CA096123 
Study First Received: August 4, 2004
Last Updated: October 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Erlotinib Hydrochloride
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antineoplastic Agents
Antirheumatic Agents
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Physiological Effects of Drugs
Protein Kinase Inhibitors
Sensory System Agents

ClinicalTrials.gov processed this record on May 26, 2016