Phase 2 Study of VELCADE Alone or VELCADE® Plus Docetaxel in Previously Treated Patients With Advanced Non-Small Cell Lung Cancer

In this study, patients with non-small cell lung cancer that is no longer responding to standard medical treatment with another anti-cancer drug will be randomly chosen to receive treatment with VELCADE alone or VELCADE in combination with docetaxel. Patients have almost equal chance of getting into either of the two treatment arms listed above.

Inclusion criteria

• Inoperable, locally advanced (Stage IIIB) or metastatic (Stage IV) NSCLC that has been histologically or cytologically confirmed.
• No more than 1 prior chemotherapy regimen.
• 18 years of age or older.
• Measurable or evaluable disease.
• KPS ≥70%.
• Life expectancy greater than 3 months.
• Female patient is either post-menopausal, surgically sterilized, or willing to use an acceptable method of birth control for the duration of the study.
• Male patient agrees to use an acceptable method of birth control for the duration of the study.
• Provide written informed consent before any study-related procedure not part of normal medical care is conducted.
• Willing and able to comply with the protocol requirements.

Exclusion criteria

• Peripheral neuropathy of Grade 2 or greater intensity, as defined by the NCI Common Toxicity Criteria (CTC):

• Grade 2: Objective sensory loss or paresthesia (including tingling), interfering with function, but not interfering with activities of daily living (ADLs).
• Grade 3: Sensory loss or paresthesia interfering with ADLs.
• Grade 4: Permanent sensory loss that interferes with function.
• Previous treatment with VELCADE.
• Previous treatment with docetaxel (prior treatment with paclitaxel will be allowed).
• Chemotherapy within 4 weeks prior to enrollment.
• Radiation therapy within 4 weeks prior to enrollment.
• Monoclonal antibodies within 6 weeks prior to enrollment.
• Any major surgery within 4 weeks prior to enrollment.
• Inadequate organ function at the Screening visit as defined by the following laboratory values:

• Platelet count ≤100,000 x 109/L
• Hemoglobin ≤8.0 g/dL
• Absolute neutrophil count (ANC) ≤1.5 x 109/L
• Aspartate transaminase (AST) ≥3 x the upper limit of the normal range (ULN)
• Alanine transaminase (ALT) ≥3 times ULN
• Creatinine ≥1.8 mg/dL
• Total bilirubin ≥2 times ULN
• Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
• No history of brain metastases or central nervous system disease.
• Active systemic infection requiring treatment.
• Treatment for a cancer other than NSCLC within 5 years prior to enrollment, with the exception of basal cell carcinoma or cervical cancer in situ.
• History of allergic reaction attributable to compounds containing boron or mannitol.
• Known to be human immunodeficiency virus (HIV)-positive. Patients assessed by the investigator to be at risk for HIV infection should be tested in accordance with local regulations.
• Known to be hepatitis B surface antigen-positive or has known active hepatitis C infection. Patients assessed by the investigator to be at risk for hepatitis B or C infection should be tested in accordance with local regulations.
• Poorly controlled hypertension, diabetes mellitus, or another serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• Pregnant or breast-feeding female patient. Confirmation that the patient is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during the Screening period. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
• Currently enrolled in another clinical research study or has received an investigational agent for any reason within 4 weeks of enrollment.