A Phase II/III Double Blind Randomized Trial of AZD2171 Versus Placebo in Patients Receiving Paclitaxel/Carboplatin Chemotherapy for the Treatment of Advanced or Metastatic Non-Small Cell Lung Cancer

Criterios de inclusión

• Negative pregnancy test
• DISEASE CHARACTERISTICS:
• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), meeting 1 of the following stage criteria:
• Stage IIIB disease
• Patients without pleural effusion who are not candidates for combined modality treatment OR who were treated at centers where combined modality treatment is not considered standard treatment are eligible
• Stage IV disease
• Measurable disease (phase II)
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by x-ray, ultrasound, physical exam, or conventional CT scan OR ≥ 10 mm by spiral CT scan
• Measurable lesions must be outside a previous radiotherapy field if they are the sole site of disease, unless disease progression has been documented
• No significant central thoracic lesion with any appreciable cavitation
• Measurable or nonmeasurable disease (phase III)
• No necrotic or hemorrhagic tumor or metastases
• No untreated brain or meningeal metastases
• CT scans are not required to rule out disease unless there is clinical suspicion of CNS disease
• Patients with previously treated stable brain metastases (by radiography or clinical exam) are eligible provided they are asymptomatic and do not require corticosteroids
• PATIENT CHARACTERISTICS:
• Performance status
• ECOG 0-1
• Life expectancy
• Not specified
• Hematopoietic
• Absolute granulocyte count ≥ 1,500/mm\^3
• Platelet count ≥ 100,000/mm\^3
• No overt bleeding (i.e., ≥ 30 mL/episode) within the past 3 months
• Hepatic
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT ≤ 2 times ULN (\< 5 times ULN if liver metastases are present)
• Renal
• Creatinine clearance ≥ 50 mL/min
• Proteinuria ≤ grade 1
• Cardiovascular
• Mean QTc ≤ 470 msec (with Bazett's correction) by ECG
• No unstable angina
• No congestive heart failure
• No myocardial infarction within the past year
• No cardiac ventricular arrhythmias requiring medication
• No history of 2nd- or 3rd-degree atrioventricular conduction defects
• No untreated or uncontrolled cardiovascular condition
• No symptomatic cardiac dysfunction
• No uncontrolled hypertension (i.e., resting blood pressure ≥ 150/100 mm Hg despite antihypertensive therapy)
• No history of labile hypertension
• No history of poor compliance with antihypertensive medication
• No history of familial long-QT syndrome
• Pulmonary
• No clinically relevant hemoptysis (i.e., ≥ 5 mL fresh blood) within the past 4 weeks
• Flecks of blood only in sputum allowed
• Other
• Not pregnant or nursing
• Fertile patients must use effective (double method for females; barrier method for males) contraception
• Able and willing to participate in the quality of life assessment
• No peripheral neuropathy \> grade 1
• No prior allergic reaction to drugs containing Cremophor EL®
• No active or uncontrolled infection
• No serious illness or medical condition which would preclude study compliance
• No inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis)
• No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or in situ cancer
• PRIOR CONCURRENT THERAPY:
• Biologic therapy
• At least 14 days since prior epidermal growth factor receptor-inhibitor therapy (e.g., tyrosine kinase inhibitor, monoclonal antibodies, vaccines, or other agents)
• No prior antiangiogenesis therapy, including any of the following:
• Bevacizumab
• Cediranib maleate
• AZD6474
• PTK787/ZK222584 (PTK/ZK)
• Sunitinib malate
• Concurrent epoetin alfa allowed
• Chemotherapy
• At least 12 months since prior adjuvant chemotherapy
• Combined chemotherapy and radiotherapy regimens for locally advanced stage IIIB disease is not considered adjuvant therapy and is not allowed
• No prior chemotherapy for metastatic or recurrent NSCLC
• Endocrine therapy
• See Disease Characteristics
• At least 1 week since prior steroids
• Radiotherapy
• See Disease Characteristics
• At least 21 days since prior radiotherapy except for low-dose non-myelosuppressive radiotherapy with approval
• Concurrent palliative radiotherapy allowed with approval
• Surgery
• At least 14 days since prior major surgery
• Other
• Recovered from prior therapy
• Prior treatment with cyclooxygenase-2 inhibitors allowed
• Concurrent prophylactic anticoagulation (e.g., warfarin) allowed provided requirements for INR are met
• No potent inhibitors of CYP3A4 and 2C8, including any of the following drugs:
• Amiodarone hydrochloride
• Clarithromycin
• Citalopram hydrobromide
• Erythromycin
• Omeprazole
• Simvastatin
• Atorvastatin
• Lovastatin
• Montelukast sodium
• Verapamil hydrochloride
• Ketoconazole
• Miconazole
• Indinovir and other antivrails
• Diltiazem
• No other concurrent experimental drug or anticancer therapy