Know Cancer

forgot password

Phase I Study of Erlotinib and Celecoxib in Former Smokers With Advanced Non-Small Cell Lung Cancer

Phase 1
18 Years
Not Enrolling
Recurrent Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

Thank you

Trial Information

Phase I Study of Erlotinib and Celecoxib in Former Smokers With Advanced Non-Small Cell Lung Cancer


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

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.

Inclusion Criteria


- 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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Clinical tolerable dose of celecoxib as measured by NCI CTCAE v3.0

Outcome Time Frame:

4 weeks

Safety Issue:


Principal Investigator

Michael Kelley

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University


United States: Food and Drug Administration

Study ID:




Start Date:

December 2003

Completion Date:

Related Keywords:

  • Recurrent Non-Small Cell Lung Cancer
  • Stage IIIB Non-Small Cell Lung Cancer
  • Stage IV Non-Small Cell Lung Cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



Duke University Medical Center Durham, North Carolina  27710