Celecoxib and Erlotinib in Treating Former Smokers With Stage IIIB or Stage IV Non-Small Cell Lung Cancer
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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. 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 |
- 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 |
| 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:
Drug: celecoxib
Given orally
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
Detailed Description:
PRIMARY OBJECTIVE:
I. To estimate the clinical toxicity and tolerability of erlotinib combined with celecoxib in patients with advanced non-small cell lung cancer (NSCLC).
SECONDARY OBJECTIVES:
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.
TERTIARY OBJECTIVES:
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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 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
More Information
No publications provided
| 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: | April 16, 2013 |
| Health Authority: | United States: Food and Drug Administration |
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 Celecoxib Erlotinib Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors |
Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Anti-Inflammatory Agents Therapeutic Uses Central Nervous System Agents Antirheumatic Agents Protein Kinase Inhibitors |
ClinicalTrials.gov processed this record on May 23, 2013