Bortezomib in Treating Patients With Stage IIIB or Stage IV Lung Cancer

Study Overview
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Brief Summary
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This phase II trial is studying how well bortezomib works in treating patients with stage IIIB or stage IV lung cancer. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the objective response rate in patients with stage IIIB or IV bronchoalveolar carcinoma (BAC) or adencarcinoma of the lung with BAC features treated with bortezomib. SECONDARY OBJECTIVES: I. Determine the progression-free and overall survival of patients treated with this drug. II. Determine the time to disease progression in patients treated with this drug. III. Determine predictors of response, based on molecular correlative studies of tumor and blood, in patients with treated with this drug. OUTLINE: This is a multicenter study. Patients are stratified according to prior epidermal growth factor receptor inhibitor therapy (yes vs no). Patients receive bortezomib IV over 3-5 seconds on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed for survival.

Official Title
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Phase II Study of Bortezomib (PS-341) for Patients With Advanced Bronchiolo-Alveolar Carcinoma (BAC) or Adenocarcinoma With BAC Features

Conditions
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Adenocarcinoma of the Lung, Bronchoalveolar Cell Lung Cancer, Non-small Cell Lung Cancer, Recurrent Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: bortezomib


Participation Criteria
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Eligibility Criteria
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Criteria: Histologically confirmed bronchoalveolar carcinoma (BAC) or adenocarcinoma of the lung with BAC features: Stage IIIB or IV disease: Patients with stage IIIB disease must be ineligible for definitive combined modality treatment with radiotherapy and chemotherapy Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques or >= 10 mm by spiral CT scan: Previously irradiated lesions are considered measurable only if lesion progressed after completion of radiotherapy No unstable brain metastases: Brain metastases that are stable for ≥ 1 month after completion of prior radiotherapy, stereotactic surgery, or surgery are allowed Performance status: ECOG 0-2 Life expectancy >3 months Hepatic: Bilirubin normal AST and ALT =< 2.5 times upper limit of normal Renal: Creatinine normal OR creatinine clearance >= 60 mL/min Cardiovascular: No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmias No more than 1 prior chemotherapy regimen for advanced BAC: Prior gefitinib or other known epidermal growth factor receptor (EGFR) inhibitors are not considered a systemic chemotherapy regimen At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) At least 4 weeks since prior corticosteroids Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception before, during, and for 30 days after completion of study treatment No ongoing or active infection No other malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer that is in complete remission No peripheral neuropathy >= grade 2 No known hypersensitivity to bortezomib, boron, or mannitol No psychiatric illness or social situation that would preclude study compliance No other uncontrolled illness No concurrent routine granulocyte colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF]) At least 2 weeks since prior radiotherapy Recovered from prior therapy (alopecia allowed) At least 2 weeks since prior EGFR inhibitors At least 4 weeks since prior anticonvulsants No prior bortezomib No concurrent antiretroviral therapy for HIV-positive patients No other concurrent investigational agents No other concurrent anticancer therapy Concurrent bisphosphonates for bone metastases allowed Hematopoietic: Absolute neutrophil count >= 1,500/mm3 Platelet count >= 100,000/mm3

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: Arm I<br>Patients receive bortezomib IV over 3-5 seconds on days 1 and 8. | Drug: bortezomib<br>* Given IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate With Bortezomib Evaluated by Both RECIST Criteria and Computer-assisted Image Analysis. | A response rate of 20% or more with bortezomib would be of interest for further evaluation, whereas a response rate of less than 5% would be of no interest. Response defined as a confirmed CR or PR. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression Free Survival using the product-limit method of Kaplan and Meier | Up to 5 years | 
| Overall Survival | Overall Suvival using the product-limit method of Kaplan and Meier. | Up to 5 years |