Bortezomib With or Without Docetaxel in Treating Patients With Relapsed or Refractory Advanced Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy such as docetaxel use different ways to stop tumor cells from dividing so they stop growing or die. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. It is not yet known whether bortezomib is more effective with or without docetaxel in treating patients with advanced non-small cell lung cancer. PURPOSE: Randomized phase II trial to compare the effectiveness of bortezomib with or without docetaxel in treating patients who have relapsed or refractory stage IIIB or stage IV non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Compare the tumor response rates (complete and partial response) in patients with relapsed or refractory advanced non-small cell lung cancer treated with bortezomib with vs without docetaxel. Secondary Compare time to progression in patients treated with these regimens. Compare the overall and 1-year survival of patients treated with these regimens. Compare the safety and tolerability of these regimens in these patients. Compare the pharmacokinetics and pharmacodynamics of these regimens in these patients. Compare the quality of life of patients treated with these regimens. OUTLINE: This is a randomized, open-label, multicenter study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Arm II: Patients receive docetaxel IV over 1 hour on day 1 and bortezomib IV as in arm I. In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving complete response (CR) receive 2 additional courses beyond confirmation of CR. Quality of life is assessed on day 1 of each treatment course (before drug administration) and at 30 days after the completion of study treatment. Patients are followed at 30 days and then every 3 months for survival. PROJECTED ACCRUAL: A total of 155 patients (75 for arm I and 80 for arm II) will be accrued for this study within 1 year.

Official Title
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A Randomized, Multicenter, Open-Label, Phase II Study Of VELCADE Alone Or VELCADE Plus Docetaxel In Previously Treated Patients With Advanced Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: bortezomib
* Drug: docetaxel


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed non-small cell lung cancer Locally advanced (stage IIIB) or metastatic (stage IV) disease Inoperable disease Relapsed or refractory disease Received 1, and only 1, prior chemotherapy regimen for locally advanced or metastatic disease Measurable or evaluable disease No symptomatic or inadequately treated brain metastases No CNS disease PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 70-100% Life expectancy More than 3 months Hematopoietic Platelet count greater than 100,000/mm^3 Hemoglobin greater than 8.0 g/dL Absolute neutrophil count greater than 1,500/mm^3 Hepatic AST and ALT less than 3 times upper limit of normal (ULN) Bilirubin less than 1.5 times ULN Hepatitis B surface antigen negative Hepatitis C negative Renal Creatinine less than 1.8 mg/dL Cardiovascular No myocardial infarction within the past 6 months No New York Heart Association class III or IV heart failure No uncontrolled angina No severe uncontrolled ventricular arrhythmias No electrocardiographic evidence of acute ischemia or active conduction system abnormalities No poorly controlled hypertension Immunologic No active systemic infection requiring treatment No prior allergic reaction attributable to compounds containing boron or mannitol HIV negative Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception No peripheral neuropathy grade 2 or greater No diabetes mellitus No other serious medical or psychiatric condition that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy More than 6 weeks since prior monoclonal antibody therapy No concurrent routine use of colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF]) No concurrent immunotherapy Chemotherapy See Disease Characteristics More than 4 weeks since prior chemotherapy No prior docetaxel Prior paclitaxel allowed No other concurrent chemotherapy Endocrine therapy No concurrent corticosteroids (e.g., prednisone or prednisolone) except dexamethasone as premedication Radiotherapy More than 4 weeks since prior radiotherapy No concurrent radiotherapy Surgery More than 4 weeks since prior major surgery No concurrent surgery for cancer management or treatment Other More than 5 years since prior treatment for any other cancer except basal cell skin cancer or carcinoma in situ of the cervix More than 4 weeks since prior investigational agents No prior bortezomib No other concurrent investigational agents No other concurrent clinical research study participation No other concurrent antineoplastic therapy No concurrent routine use of anti-inflammatory drugs, including cyclo-oxygenase inhibitors (e.g., celecoxib or rofecoxib)

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Velcade Alone<br>Velcade | Drug: bortezomib<br> <br> |
| Experimental: Velcade plus Docetaxel<br>Velcade plus Docetaxel | Drug: bortezomib<br> <br> Drug: docetaxel<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

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