A Phase II Study of OSI 774 (IND Number 63383) in Combination With Celecoxib (Celebrex, Pharmacia) as Second-Line Therapy in Advanced Non-Small Cell Lung Cancer
A Phase II Study of OSI 774 (IND Number 63383) in Combination With Celecoxib (Celebrex, Pharmacia) as Second-Line Therapy in Advanced Non-Small Cell Lung Cancer
This phase II trial is studying how well giving erlotinib together with celecoxib works in treating patients with recurrent stage IIIB or stage IV non-small cell lung cancer. Erlotinib and celecoxib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Celecoxib may slow the growth of a tumor by stopping blood flow to the tumor. Combining erlotinib with celecoxib may kill more tumor cells.
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PRIMARY OBJECTIVES:
I. Determine the response rate of patients with stage IIIB or IV recurrent non-small cell lung cancer treated with erlotinib and celecoxib as second-line therapy.
SECONDARY OBJECTIVES:
I. Determine the time to progression in patients treated with this regimen. II. Determine the survival duration of patients treated with this regimen. III. Determine the toxicity of this regimen in these patients. IV. Correlate the expression of epidermal growth factor receptor and cyclooxygenase-2 in tumor specimens with response, time to progression, and survival in patients treated with this regimen.
OUTLINE: Patients are assigned to 1 of 2 treatment groups.
Group 1: Patients receive oral erlotinib once daily and oral celecoxib twice daily.
Group 2: Patients receive erlotinib as in group 1.
Treatment in both groups continues in the absence of disease progression or unacceptable toxicity.
Patients are followed every 2 months.
PROJECTED ACCRUAL: A total of 40-80 patients will be accrued for this study within 10 months.
Inclusion Criteria:
Histologically or cytologically confirmed non-small cell lung cancer
Recurrent disease that has progressed after 1 or 2 prior chemotherapy regimens (platinum- or nonplatinum-based)
At least 1 unidimensionally measurable lesion*
Must have tissue specimen available for assays
No brain metastases
Performance status - ECOG 0-2
Performance status - Karnofsky 60-100%
More than 3 months
WBC at least 3,000/mm^3
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Bilirubin normal
AST/ALT no greater than 2.5 times upper normal limit (ULN)
Creatinine normal
Creatinine clearance at least 60 mL/min
No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia
No prior abnormalities of the cornea (e.g., dry eye syndrome or Sjögren's syndrome)
No congenital abnormality (e.g., Fuch's dystrophy)
No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)
No abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production test)
Able to ingest oral medication
No requirement for IV alimentation
No history of peptic ulcer disease
No active gastrointestinal ulcers
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No other concurrent uncontrolled illness
No ongoing or active infection
No significant traumatic injury within the past 21 days
No psychiatric illness or social situation that would preclude study compliance
No prior allergic reactions to sulfonamides, aspirin, and other nonsteroidal anti-inflammatory drugs
No prior monoclonal antibodies to epidermal growth factor receptor (EGFR)
More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
No concurrent chemotherapy
No concurrent glucocorticoids
More than 4 weeks since prior radiotherapy and recovered
More than 21 days since prior major surgery
No prior surgery affecting absorption
No prior EGFR-specific tyrosine kinases
No concurrent anticonvulsants
No other concurrent investigational agents
No concurrent antiretroviral therapy for HIV-positive patients
No concurrent antacids
No concurrent administration of any of the following drugs: