Gefitinib and Celecoxib in Treating Patients With Refractory Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Celecoxib may slow the growth of cancer by stopping blood flow to the tumor. Combining gefitinib with celecoxib may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining gefitinib with celecoxib in treating patients who have non-small cell lung cancer that is refractory to platinum-based chemotherapy (such as cisplatin or carboplatin).

Detailed Description
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OBJECTIVES: Primary Determine the response rate in patients with platinum-refractory non-small cell lung cancer treated with gefitinib and celecoxib. Secondary Determine the progression-free and overall survival of patients treated with this regimen. Determine the toxicity of this regimen in these patients. OUTLINE: Patients receive oral gefitinib once daily and oral celecoxib twice daily on days 1-28. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients are followed for up to 6 weeks. PROJECTED ACCRUAL: A total of 18-27 patients will be accrued for this study within 22 months.

Official Title
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Phase II Study of the Combination of ZD1839 (Iressa) and Celecoxib in Patients With Platinum Refractory Non-Small Cell Lung Cance

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Celecoxib
* Drug: ZD1839


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) Progression of disease during platinum-based (cisplatin or carboplatin) chemotherapy or within 3 months of completing chemotherapy Treatment with other agents since prior platinum-based chemotherapy allowed Measurable disease Target lesions within a prior radiation field must have documented evidence of progression at least 8 weeks after the completion of radiotherapy No active brain or leptomeningeal metastases Treated brain metastases allowed at least 4 weeks after the completion of appropriate therapy PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 8 g/dL Hepatic Bilirubin no greater than upper limit of normal (ULN) AST/ALT no greater than 2.5 times ULN (if alkaline phosphatase is no greater than ULN) Alkaline phosphatase no greater than 5 times ULN (if AST and ALT are greater than ULN) No history of chronic hepatitis Renal Creatinine no greater than 1.5 times ULN Cardiovascular No active thromboembolic event within the past 4 weeks No uncontrolled congestive heart failure No uncontrolled angina No myocardial infarction and/or stroke within the past 6 months Pulmonary No evidence of clinically active interstitial lung disease Gastrointestinal No history of gastrointestinal bleeding within the past 6 months No history of peptic ulcer disease Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Must weigh at least 110 pounds (50 kg) HIV negative No allergy to sulfonamides No allergy to any NSAID, including celecoxib No known severe hypersensitivity to gefitinib or any of its excipients No other malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix No history of dementia, active psychiatric disorder, or any other condition that would preclude study compliance No other concurrent serious medical condition PRIOR CONCURRENT THERAPY: Biologic therapy No prior epidermal growth factor receptor inhibitor No concurrent biologic therapy Chemotherapy See Disease Characteristics More than 2 weeks since prior chemotherapy Endocrine therapy Not specified Radiotherapy Recovered from prior radiotherapy Surgery Recovered from prior surgery Other Recovered from prior therapy More than 2 weeks since prior investigational therapy More than 1 week since prior fluconazole More than 30 days since prior participation in another investigational agent clinical trial More than 30 days since prior chronic nonsteroidal anti-inflammatory drugs (NSAIDs), including celecoxib or rofecoxib No prior gefitinib No prior cyclooxygenase-2 (COX-2) inhibitor or another clinical trial for NSCLC No other concurrent NSAIDs Concurrent aspirin allowed (not to exceed 325 mg/day) No other concurrent COX-2 inhibitors No concurrent lithium No concurrent fluconazole No concurrent use of any of the following: Phenytoin Carbamazepine Barbiturates Rifampin Phenobarbital Hypericum perforatum

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Celecoxib & ZD1839<br>Celecoxib: 400mg orally two times a day, taken with meals. ZD1839: 250 mg po every day, taken with or without food. | Drug: Celecoxib<br>* Celecoxib 400mg orally two times a day, taken with meals.<br>* Other names: Celebrex;Drug: ZD1839<br>* ZD1839 250 mg po every day, taken with or without food.<br>* Other names: Gefitinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | CT scan chest/abdomen; Assessments of complete response (CR) or partial response (PR)require confirmation 4 weeks or later. | Every 2 cycles; after the 1st 4 cycles, every month by clinical exam & every 3 months radiological evaluation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) |  | Every 2 cycles; after the 1st 4 cycles, every month by clinical exam & every 3 months radiological evaluation | 
| Overall survival |  | Every 2 cycles; after the 1st 4 cycles, every month by clinical exam & every 3 months radiological evaluation | 
| Toxicity of this drug combination |  | Every 2 weeks; Every month after 4 cycles if the patient has not developed > Grade 2 toxicity | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent non-small cell lung cancer