CALGB 30607 - Randomized, Phase III, Placebo-Controlled Trial of Sunitinib as Maintenance Therapy in Non-Progressing Pts Following an Initial Four Cycles of Platinum-Based Combination Chemotherapy in Advanced, Stage IIIB/IV Non-Small Cell Lung Cancer
The purpose of this study is to determine whether or not giving you a drug called sunitinib after you respond to chemotherapy (your tumor shrinks or stops growing) will help your tumor continue to shrink, or stay the same. Sunitinib is experimental (investigational) in the treatment of non-small cell lung cancer. Standard treatment for your type of cancer would be to stop chemotherapy treatment after you receive your initial therapy.
Histologic Documentation: Histologic or cytologic documentation of primary non-small cell lung cancer.
Advanced Disease: Stage IIIB or IV disease patients who are not candidates 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, must have received definitive therapy (greater or equal to 6 weeks since resection or greater or equal to 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.
Patients must have received one chemotherapy regimen for stage IIIB or IV NSCLC. The regimen must include four cycles of platinum-based doublet chemotherapy with or without bevacizumab (bevacizumab may not be given beyond the fourth cycle of chemotherapy). Patients must have achieved a complete response, partial response, or stable disease to first-line chemotherapy and have no evidence of disease progression. At least 3 weeks, and no more than 5 weeks, must have elapsed from the completion of 4 cycles of therapy to registration.
No prior adjuvant chemotherapy for stage I-III resected NSCLC or combined modality therapy for stage III NSCLC,
No other primary therapy (including experimental therapy) for NSCLC, Palliative radiation therapy must have been completed at least one week before planned start of protocol therapy.
Patients must have Measurable or Non-measurable Disease
Lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater or equal to 2 cm with conventional techniques or as a greater or equal to 1 cm with spiral CT
All other lesions, including small lesions (longest diameter less than 20 mm with conventional techniques or less than 10 mm with spiral CT scan) and truly non- measurable lesions.
Lesions that are considered non-measurable include the following:
- Bone lesions
- Leptomeningeal disease
- Pleural/pericardial effusion
- Lymphangitis cutis/pulmonis
- Abdominal masses that are not confirmed and followed by imaging techniques
- Cystic lesions
Age - 18 years or older.
ECOG performance status 0 or 1.
Non-pregnant and non-nursing,
No ongoing cardiac dysrhythmias, atrial fibrillation, or history of QTc interval > 500 msec (within 2 years prior to registration). The use of agents with proarrhytbmic potential (e.g., quinidine, procainamide, disopyramide, sotalol, probucol, haloperidol, risperidone, indapamide, flecainide) is not recommended while on protocol therapy. A comprehensive list of agents with proarrhythmic potential can be found at http: / / torsades.org.
Patients with Class 1 NYHA heart failure are eligible. Patients with a history of Class II NYHA heart failure are eligible, provided they meet at least one of the following criteria
- Patients with a history of Class II heart failure who are asymptomatic on treatment.
- Patients with prior anthracycline exposure.
- Patients who have received central thoracic radiation that included the heart in the radiotherapy port.
Patients with a history of Class II or IV NYHA heart failure within 12 months prior to registration are not eligible.
No myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft or stenting, cerebrovascular accident or transient ischemic attack within the last year.
Patients with hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy) are not eligible.
Patients who require use of therapeutic anticoagulation for thromboembolic disease are not eligible. Note: low doses of coumadin (up to 2 mg daily) are permitted for prophylaxis of thrombosis.
No history of venous thrombosis, pulmonaiy embollsxn, or hypercoagulopathy syndrome.
No history of pulmonary hemorrhage, bleeding diathesis, or evidence of hemoptysis.
Patients with blood-tinged or blood-streaked sputum will be permitted on study if the hemoptysis amounts to less than 5 ml of blood per episode and less than 10 ml of blood per 24-hour period in the best estimate of the investigator.
Patients with a history of hypothyroidism are eligible, provided they are currently euthyroid.
None of the following within 28 days of beginning treatment: abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, serious or non-healing wound, ulcer, or bone fracture.
The use of the following specific inhibitors and inducers of CYP3A4 is not permitted. The following inhibitors of CYP3A4 are prohibited within 7 days before beginning and during treatment with sunitinib azole antifungals (ketoconazole, itraconozole), diltiazem, clarithromycin, erythromycin, verapamil, delavirdine, and HW protease inhibitors (indinavir, saquinavir, ritonavir, atazanavir, nelfinav’ir), The following inducers of CYP3A4 are prohibited wIthin 12 days before beginning and during treatment with sunitinib rifampin, rifabutin, carbamazepine, phenobarbital, phenytoin, St. Johns Wort, efavirenz, tipranavir. Other inhibitors and inducers of CYPSA4 may be used if necessary, but their use is discouraged.
Patients unable to take oral medication are not eligible
Lab Values: Granulocytes = 1,500/mcl
- Platelets = 100,000/mcl
- Total bilirubin = 1.5 x ULN
- AST (SGOT) = 2.5 x ULN
- (Pts w/ liver mets may have AST = 5 x ULN; all other pts AST
= 2.5 x ULN)
- Creatinine = 1.5 mg/dl
Nancy N. and J.C. Lewis Cancer & Research Pavilion
Nancy N. and J.C. Lewis Cancer & Research Pavilion225 Candler Drive, Savannah, Georgia 31405