| Study Summary: |
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PRIMARY OBJECTIVES:
I. To compare the effect of sunitinib malate vs placebo on the progression-free survival of
patients with stage IIIB or IV non-small cell lung cancer who have stable or responding
disease after prior treatment with 4 courses of platinum-based therapy.
SECONDARY OBJECTIVES:
I. To compare the toxicity of these regimens when administered in the maintenance setting.
II. To evaluate the additional response rate to sunitinib malate when administered in the
maintenance setting.
III. To compare the overall survival of patients treated with these regimens.
OUTLINE: This is a multicenter study. Patients are stratified according to ECOG performance
status (0 vs 1), disease stage (IIIB vs IV), prior treatment with bevacizumab (yes vs no),
and gender. Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive oral sunitinib malate once daily on days 1-21. Courses repeat every
21 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive oral placebo once daily on days 1-21. Courses repeat every 21 days
in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months for 1 year, every
6 months for 1 year, and periodically for 3 years.
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| Criteria: |
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Inclusion Criteria:
- Histologically or cytologically confirmed primary non-small cell lung cancer (NSCLC)
- Stage IIIB or IV disease
- Not a candidate for combined modality therapy (chemoradiotherapy)
- No evidence of symptomatic or untreated brain metastases, spinal cord compression, or
carcinomatous meningitis
- Patients with CNS metastases must be asymptomatic, received definitive therapy
(≥ 6 weeks since resection or ≥ 2 weeks since radiotherapy) for brain
metastases, and be off steroids or on a stable dose for 2 weeks prior to
registration
- No cavitary lesions
- Must have received one prior first-line chemotherapy regimen that included 4 courses
of platinum-based doublet chemotherapy with or without bevacizumab (bevacizumab may
not have been given beyond the fourth course of chemotherapy)
- Must have achieved a complete response, partial response, or stable disease to
first-line chemotherapy and have no evidence of disease progression
- Completed the fourth course of first-line chemotherapy 3-5 weeks prior to study
entry
- Measurable or nonmeasurable disease
- Measurable disease is defined as ≥ 1 unidimensionally measurable lesion ≥ 2 cm
by conventional techniques or ≥ 1 cm by spiral CT scan
- Nonmeasurable disease is defined as all other lesions, including small lesions
(longest diameter < 20 mm by conventional techniques or < 10 mm by spiral CT
scan), truly nonmeasurable lesions, and any of the following:
- Bone lesions
- Leptomeningeal disease
- Ascites
- Pleural/pericardial effusion
- Lymphangitis cutis/pulmonis
- Abdominal masses that are not confirmed and followed by imaging techniques
- Cystic lesions
- ECOG performance status 0-1
- Granulocyte count ≥ 1,500/mcL
- Platelet count ≥ 100,000/mcL
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST ≤ 2.5 times ULN (or ≤ 5 times ULN for patients with liver metastases)
- Creatinine ≤ 1.5 mg/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Able to take oral medication
- No history of QTc interval ≥ 500 msec within the past 2 years
- No ongoing cardiac dysrhythmias or atrial fibrillation
- No myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass
graft or stenting, cerebrovascular accident, or transient ischemic attack within the
past year
- No hypertension that cannot be controlled by medications (i.e., > 150/100mm Hg
despite optimal medical therapy)
- No history of New York Heart Association (NYHA) class III-IV heart failure within the
past 12 months
- NYHA class I heart failure allowed
- History of NYHA class II heart failure allowed provided at least one of the
following criteria are met:
- Asymptomatic on treatment
- Previously treated with an anthracycline
- Previously treated with central thoracic radiotherapy that included the
heart in the radiotherapy port
- No history of venous thrombosis, pulmonary embolism, or hypercoagulopathy syndrome
- No history of pulmonary hemorrhage, bleeding diathesis, or evidence of hemoptysis
- Patients with blood-tinged or blood-streaked sputum are eligible provided the
hemoptysis amounts to < 5 mL of blood per episode and < 10 mL of blood per
24-hour period, in the best estimate of the investigator
- No abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, or
serious or non-healing wound, ulcer, or bone fracture within the past 28 days
- History of hypothyroidism allowed provided patient is currently euthyroid
- No concurrent hormonal therapy, except steroids for adrenal failure, hormones for
non-disease-related conditions (e.g., insulin for diabetes), or intermittent
dexamethasone as an antiemetic
- No prior adjuvant chemotherapy for resected stage I-III NSCLC or combined modality
therapy for stage III NSCLC
- No other prior primary therapy (including experimental therapy) for NSCLC
- At least 1 week since prior palliative radiotherapy
- More than 7 days since prior and no concurrent CYP3A4 inhibitors, including any of
the following:
- Azole antifungals (ketoconazole, itraconazole)
- Diltiazem
- Clarithromycin
- Erythromycin
- Verapamil
- Delavirdine
- HIV protease inhibitors (indinavir, saquinavir, ritonavir, atazanavir,
nelfinavir)
- More than 12 days since prior and no concurrent CYP3A4 inducers, including any of the
following:
- Rifampin
- Rifabutin
- Carbamazepine
- Phenobarbital
- Phenytoin
- Hypericum perforatum (St. John's wort)
- Efavirenz
- Tipranavir
- No concurrent agents with proarrhythmic potential, including any of the following:
- Quinidine
- Procainamide
- Disopyramide
- Sotalol
- Probucol
- Haloperidol
- Risperidone
- Indapamide
- Flecainide
- No concurrent therapeutic anticoagulation for thromboembolic disease
- Concurrent low-dose coumadin (≤ 2 mg/day) allowed for prophylaxis of thrombosis
- No concurrent chemotherapy or radiotherapy
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