RATIONALE: 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.

PURPOSE: 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.

Condition	Intervention	Phase
Non-small cell lung cancer	Drug: bortezomib  Drug: cetuximab  Drug: docetaxel  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy  Procedure: monoclonal antibody therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the progression-free survival of patients with stage IIIB or IV non-small cell lung cancer and performance status 2 treated with docetaxel in combination with either cetuximab or bortezomib as first-line therapy.

Secondary

• Determine the overall response rate in patients treated with these regimens.
• Determine the overall survival distribution of patients treated with these regimens.
• Determine the toxic effects of these regimens in these patients.

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), including any of the following cellular subtypes:
• Adenocarcinoma
• Large cell
• Squamous cell
• Mixture of the above cellular types
• Meets 1 of the following stage criteria:
• Stage IIIB disease with a malignant pleural effusion or supraclavicular node involvement
• Patients who are eligible for CALGB protocols of combined chemotherapy and thoracic radiotherapy are not eligible for this study
• Stage IV disease
• ECOG performance status 2
• Measurable or nonmeasurable disease
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
• The following are considered nonmeasurable disease:
• Bone lesions
• Ascites
• Pleural or pericardial effusion
• Lymphangitis cutis or pulmonis
• Abdominal masses that are not confirmed and followed by imaging techniques
• Cystic lesions
• No untreated CNS metastases
• Patients with known CNS metastases who have received prior therapy (e.g., surgery, radiotherapy, or gamma knife radiosurgery) are eligible provided both of the following criteria are met:
• Neurologically stable and off steroids
• Not on enzyme-inducing anticonvulsants
• No leptomeningeal disease

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• See Disease Characteristics

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• AST normal
• Bilirubin normal

Renal

• Creatinine normal

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for up to 5 weeks after completion of study treatment
• No peripheral neuropathy ≥ grade 2
• No history of severe infusion reaction to a monoclonal antibody

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• No other concurrent chemotherapy

Endocrine therapy

• See Disease Characteristics
• No concurrent hormonal therapy except megestrol for appetite stimulation

Radiotherapy

• See Disease Characteristics
• Recovered from prior radiotherapy
• No concurrent palliative radiotherapy

Surgery

• See Disease Characteristics
• Recovered from prior surgery

Other

• At least 12 months since prior treatment for early-stage or locally advanced stage III NSCLC
• No prior systemic treatment for advanced NSCLC
• No prior treatment that specifically and directly targets the epidermal growth factor receptor pathway
• No other concurrent investigational therapy

Please refer to this study by ClinicalTrials.gov identifier  NCT00118183

Study chairs or principal investigators

Rogerio C. Lilenbaum, MD,  Study Chair,  Mount Sinai Comprehensive Cancer Center at Mount Sinai Medical Center   

Study ID Numbers:  CDR0000433338; CALGB-30402; NCT00118183
Record last reviewed:  June 2005
Last Updated:  July 25, 2005
Record first received:  July 8, 2005
ClinicalTrials.gov Identifier:  NCT00118183
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-07-26