Docetaxel With Either Cetuximab or Bortezomib as First-Line Therapy in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This randomized phase II trial is studying how well giving docetaxel together with either cetuximab or bortezomib works as first-line therapy in treating patients with stage III or stage IV non-small cell lung cancer. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving docetaxel together with either cetuximab or bortezomib may be effective as first-line therapy in treating non-small cell lung cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the progression free survival (PFS), defined as the time between study entry and disease progression or death, for each of the two combination regimens. SECONDARY OBJECTIVES: I. To determine the overall response rate of each regimen. II. To evaluate the overall survival distributions associated with each regimen. III. To evaluate the toxicities of each regimen. OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive docetaxel IV over 30 minutes on days 1, 8, and 15 and cetuximab IV over 1-2 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease after 4 courses receive cetuximab alone as above in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive docetaxel as in arm I and bortezomib IV over 3-5 seconds on days 1, 8, and 15. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease after 4 courses receive bortezomib alone as above in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed monthly for 1 year, every 2 months for 2 years, and then every 4 months for 3 years. PROJECTED ACCRUAL: A total of 62 patients (31 per treatment arm) will be accrued for this study within 6-11 months.

Official Title
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A Phase II Trial of Docetaxel Plus Cetuximab and Docetaxel Plus Bortezomib (NSC #681239, IND #58443) in Advanced Non-Small Cell Lung Cancer Patients With Performance Status (PS) 2

Conditions
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Adenocarcinoma of the Lung, Adenosquamous Cell Lung Cancer, Large Cell Lung Cancer, Malignant Pleural Effusion, Recurrent Non-small Cell Lung Cancer, Squamous Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: docetaxel
* Biological: cetuximab
* Drug: bortezomib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients must have histologically or cytologically documented non-small cell carcinoma of the lung (adenocarcinoma, large cell, squamous, or mixtures of these types) Patients with stage IV disease are eligible Patients with stage IIIB due to a malignant pleural effusion or supraclavicular node involvement are eligible (IIIB patients eligible for CALGB protocols of combined chemotherapy and thoracic radiotherapy are not eligible) Patients with known CNS metastases who have received therapy (surgery, XRT, gamma knife), and are neurologically stable and off steroids by the time of enrollment are eligible if they are not on enzyme-inducing anticonvulsants; patients with leptomeningeal disease are not eligible Documentation of PS 2 must be noted on form C-1392 Patients must have measurable or non-measurable disease Measurable disease (target lesions): lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan Non-measurable disease (non-target lesions): all other lesions, including small lesions (longest diameter < 20 mm with conventional techniques or < 10 mm with spiral CT scan) and truly nonmeasurable lesions; lesions that are considered non-measurable include the following: Bone lesions Ascites Pleural/pericardial effusion Lymphangitis cutis/pulmonis Abdominal masses that are not confirmed and followed by imaging techniques Cystic lesions No prior systemic treatment for advanced NSCLC is permitted; prior treatment for early-stage disease (adjuvant) or for locally-advanced stage III disease is allowed if completed at least 12 months prior to registration Patients must have recovered (all toxicities ≤ grade 1) from prior surgery and/or radiotherapy No prior therapy which specifically and directly targets the EGFR pathway No prior severe infusion reactions to a monoclonal antibody No ≥ grade 2 peripheral neuropathy Non-pregnant and non-nursing No concurrent treatment with any other investigational therapy Granulocytes ≥ 1,500/μl Platelets ≥ 100,000/μl Serum creatinine ≤ ULN Bilirubin ≤ ULN AST ≤ ULN

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive docetaxel IV over 30 minutes on days 1, 8, and 15 and cetuximab IV over 1-2 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease after 4 courses receive cetuximab alone as above in the absence of disease progression or unacceptable toxicity. | Drug: docetaxel<br>* Given IV<br>* Other names: TXT;Biological: cetuximab<br>* Given IV<br>* Other names: monoclonal antibody C225;|
| Experimental: Arm II<br>Patients receive docetaxel as in arm I and bortezomib IV over 3-5 seconds on days 1, 8, and 15. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease after 4 courses receive bortezomib alone as above in the absence of disease progression or unacceptable toxicity. | Drug: docetaxel<br>* Given IV<br>* Other names: TXT;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 |
| --- | --- | --- |
| PFS | The product limit estimator developed by Kaplan and Meier will be used. | Time between randomization and initial failure (disease progression or death), assessed up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | An exact binomial 95% confidence interval will be computed for these estimates. | Up to 6 years | 
| Overall survival | The product limit estimator developed by Kaplan and Meier will be used. | Time between randomization and death, assessed up to 6 years |