Gefitinib With or Without Carboplatin and Paclitaxel in Treating Older Patients With Unresectable or Metastatic Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Biological therapies such as gefitinib may interfere with the growth of cancer cells and slow the growth of the tumor. Drugs used in chemotherapy such as carboplatin and paclitaxel use different ways to stop tumor cells from dividing so they stop growing or die. Combining gefitinib with carboplatin and paclitaxel may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving gefitinib alone or together with carboplatin and paclitaxel works in treating older patients with unresectable or metastatic non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Determine the 6-month progression status of older patients with unresectable or metastatic non-small cell lung cancer treated with gefitinib alone or with carboplatin and paclitaxel. Secondary Determine the response rate in patients treated with these regimens. Determine the quality of life of patients treated with these regimens. Determine whether serum-secreted or soluble epidermal growth factor receptor (EGFR) concentrations predict response in patients treated with these regimens. Correlate the presence of social support for these patients with toxicity and efficacy of these regimens. Determine whether social support for these patients differs according to gender. Determine the reasons an oncologist would choose a chemotherapy vs a nonchemotherapy regimen for these patients. Tertiary Correlate EGFR signaling pathway markers, RNA expression profile, gene polymorphisms of prespecified germline and tumor genes, and plasma and urine proteomic patterns with response rate and time to progression of patients receiving treatment in group I. OUTLINE: This is a nonrandomized, multicenter study. Patients are assigned to 1 of 2 treatment groups as determined by their treating physician. Group I: Patients receive oral gefitinib on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Group II: Patients receive paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of chemotherapy and in the absence of disease progression, patients receive oral gefitinib as in group I. Quality of life is assessed at baseline and after the completion of course 2. Patients are followed every 3 months for 5 years. PROJECTED ACCRUAL: A total of 107 patients (51 for group I and 56 for group II) will be accrued for this study within 1.7 years.

Official Title
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Parallel Phase II Trials of ZD1839 (Iressa) Alone or Weekly Carboplatin and Paclitaxel Followed by ZD1839 (Iressa) (Oncologists Must Choose) for Metastatic Non-Small Cell Lung Cancer in Patients > or = 65 Years of Age

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: carboplatin
* Drug: gefitinib
* Drug: paclitaxel


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) Metastatic or unresectable disease Measurable disease At least 1 lesion at least 2.0 cm Disease must be completely outside prior radiotherapy port OR documented disease progression since the completion of radiotherapy No meningeal carcinomatosis No untreated brain metastases Current metastatic CNS disease must have been treated and clinically stable for at least 2 weeks prior to study chemotherapy No potentially curative treatment options available (e.g., chemotherapy with surgery or radiotherapy) PATIENT CHARACTERISTICS: Age 65 and over Performance status ECOG 0-2 Life expectancy At least 12 weeks Hematopoietic Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 10.0 g/dL Hepatic Bilirubin no greater than 2.0 mg/dL No uncontrolled hepatic disease Renal Creatinine no greater than 2 times upper limit of normal No uncontrolled renal disease Cardiovascular No uncontrolled cardiac disease Pulmonary No clinically active interstitial lung disease Asymptomatic, chronic stable radiographic changes allowed No uncontrolled respiratory disease Other Fertile patients must use effective contraception Able and willing to complete questionnaires alone or with assistance No known hypersensitivity to gefitinib or any of its excipients No active infection within the past 2 weeks No other prior malignancy within the past 5 years except basal cell skin cancer No grade 2 or greater peripheral neuropathy (CTC v2.0) No uncontrolled diabetes mellitus (for patients receiving study chemotherapy) No dysphagia or inability to swallow intact capsules No significant medical condition that would preclude study treatment or follow-up No severe or uncontrolled systemic disease PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy See Disease Characteristics No prior chemotherapy for metastatic NSCLC Endocrine therapy Concurrent steroids allowed provided the dose is not changed Radiotherapy See Disease Characteristics At least 3 weeks since prior radiotherapy and recovered No prior radiotherapy to more than 25% of marrow-containing skeleton No concurrent radiotherapy (including palliative) Surgery See Disease Characteristics At least 3 weeks since prior major surgery No surgery within 7 days after study participation Other More than 30 days since prior non-FDA approved investigational drugs No concurrent oral retinoids No concurrent CYP3A4-inducing agents, including the following: Carbamazepine Oxcarbazepine Modafinil Ethosuximide Griseofulvin Nafcillin Phenobarbital Phenylbutazone Phenytoin Primidone Rifampin Hypericum perforatum (St. John's wort) Barbiturates Sulfinpyrazone No concurrent drugs that cause sustained elevation of gastric pH (≥ 5) No concurrent antacids within 4 hours before, during, and within 4 hours after gefitinib administration No concurrent itraconazole, fluconazole, ketoconazole, or erythromycin

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 120 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: gefitinib<br>Patients receive oral gefitinib on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline and after the completion of course 2. Patients are followed every 3 months for 5 years. | Drug: gefitinib<br> <br> |
| Experimental: paclitaxel + carboplatin + gefitinib<br>Patients receive paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of chemotherapy and in the absence of disease progression, patients receive oral gefitinib as in group I. Quality of life is assessed at baseline and after the completion of course 2. Patients are followed every 3 months for 5 years. | Drug: carboplatin<br> <br> Drug: gefitinib<br> <br> Drug: paclitaxel<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression status at 6 months |  | at 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed response rate (complete or partial response) |  | Up to 5 years | 
| Overall survival |  | Up to 5 years | 
| Progression-free survival |  | Up to 5 years | 
| Quality of life as assessed by the Lung Cancer Symptom scale |  | Up to 5 years | 
| Social support measure as assessed by the Lubben Social Network scale |  | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV non-small cell lung cancer, stage IIIB non-small cell lung cancer