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

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.

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)