Bortezomib in Treating Patients With Advanced Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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Phase II trial to study the effectiveness of bortezomib in treating patients who have stage IIIB, stage IV, or recurrent non-small cell lung cancer. Bortezomib may interfere with the growth of tumor cells by blocking certain enzymes necessary for tumor cell growth

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the response rate, time to progression, and survival of patients with advanced non-small cell lung cancer treated with bortezomib. II. Determine the toxicity of this drug in these patients. III. Correlate toxicity and activity of this drug with markers of proteasome inhibition in blood and peripheral mononuclear cells in these patients. OUTLINE: Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who received prior bortezomib and achieved at least a partial response of at least 6 months duration may also receive therapy as above.

Official Title
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A Phase II Study Of PS-341 In Metastatic Non-Small Cell Lung Cancer

Conditions
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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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Inclusion Criteria: Histologically or cytologically confirmed non-small cell lung cancer Mixed tumors allowed unless small cell elements are present Stage IIIB or IV or recurrent disease At least 1 measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan No known brain metastases Performance status - ECOG 0-1 More than 3 months Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Bilirubin ≤ 2 mg/dL AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver involvement present) Creatinine ≤ 2 mg/dL Creatinine clearance ≥ 60 mL/min No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No peripheral neuropathy > grade 1 No other concurrent uncontrolled illness No ongoing or active infection No psychiatric illness or social situation that would preclude study participation No more than 1 prior chemotherapy regimen Two prior chemotherapy regimens allowed provided 1 of the 2 regimens was gefitinib monotherapy as second-line therapy At least 4 weeks since prior chemotherapy (6 weeks for carmustine, mitomycin, or nitrosoureas) and recovered At least 4 weeks since prior radiotherapy (except localized radiotherapy for symptom relief) and recovered Prior bortezomib allowed provided patient achieved at least a partial response (of at least 6 months duration), received no other therapy since the last dose of bortezomib, and has no residual toxicity greater than grade 1 No other concurrent investigational or commercial agents or therapies for malignancy

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: Treatment (bortezomib)<br>Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who received prior bortezomib and achieved at least a partial response of at least 6 months duration may also receive therapy as above. | Drug: bortezomib<br>* Given IV<br>* Other names: VELCADE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate to PS-341 therapy |  | Up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Kaplan-Meier estimates of survival (overall, progression free) and 95% confidence intervals will be calculated. | Up to 4 months | 
| Overall survival | Kaplan-Meier estimates of survival (overall, progression free) and 95% confidence intervals will be calculated. | Up to 4 hours |