Sunitinib Malate as Maintenance Therapy in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer Previously Treated With Combination Chemotherapy

Tracking Information
First Submitted Date ICMJE	June 6, 2008
First Posted Date ICMJE	June 9, 2008
Results First Submitted Date	December 8, 2016
Results First Posted Date	February 2, 2017
Last Update Posted Date	August 10, 2017
Study Start Date ICMJE	June 2008
Actual Primary Completion Date	November 2013 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: July 11, 2017)	Progression Free Survival (PFS) [ Time Frame: Time from randomization to disease progression and death of any cause, whichever comes first (up to 5 years) ]; Progression Free Survival (PFS) was defined as the time from randomization until disease progression or death, whichever occurs first. The median PFS with 95% CI was estimated using the Kaplan-Meier method. Progression is defined as in the primary outcome measure.
Original Primary Outcome Measures ICMJE; (submitted: June 6, 2008)	Progression-free survival
Change History	Complete list of historical versions of study NCT00693992 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: July 11, 2017)	Overall Survival (OS) [ Time Frame: Time from randomization to death (up to 5 years) ]Overall survival (OS) is defined as the time from patient randomization to death from any cause. The median OS with 95% CI was estimated using the Kaplan-Meier method.; Response Rate (RR) [ Time Frame: Duration of treatment (up to 5 years) ]The percentage of patients who respond (completely or partially) to each combination regimen will be estimated. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions.; Percentage of Deterioration in QOL at 3 Months Using the EORTC QLQ-C30 Global Health Subscale [ Time Frame: At 3 months ]The percentage of patients with at least a 10% drop in the EORTC-QLQ-C30 Global Health Subscale score from baseline to 3-months. The difference between groups will be tested using Fisher's exact test.; Percentage of Deterioration in Symptom Progression at 3 Months Using the EORTC LC13 Dyspnea Subscale [ Time Frame: At 3 months ]The percentage of patients with at least a 10% drop in the EORTC LC13 Dyspnea Subscale score from baseline to 3-months. The difference between groups will be tested using Fisher's exact test.; Grade and Type of Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [ Time Frame: Duration of study (up to 5 years) ]Grade 3 or 4 adverse events which affected more than 5% of participants are summarized by arm.
Original Secondary Outcome Measures ICMJE; (submitted: June 6, 2008)	Grade and type of toxicity; Response rate; Overall survival
Current Other Outcome Measures ICMJE; (submitted: July 11, 2017)	VEGF Levels and Correlation With Clinical Outcomes, Including RR, PFS, and OS [ Time Frame: Up to 6 weeks ]
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Sunitinib Malate as Maintenance Therapy in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer Previously Treated With Combination Chemotherapy
Official Title ICMJE	Randomized, Phase III, Double-Blind Placebo-Controlled Trial of Sunitinib (NSC #736511) as Maintenance Therapy in Non-progressing Patients Following an Initial Four Cycles of Platinum-Based Combination Chemotherapy in Advanced, Stage IIIB / IV Non-small Cell Lung Cancer
Brief Summary	This randomized phase III trial studies sunitinib malate to see how well it works when given as maintenance therapy (meaning it is approved for treatment after chemotherapy) in patients with stage IIIB-IV non-small cell lung cancer who have responded to prior treatment with combination chemotherapy. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking the growth of new blood vessels necessary for tumor growth. It is not yet known whether sunitinib malate is effective in helping tumors continue to shrink or stop growing.
Detailed Description	PRIMARY OBJECTIVES: I. To evaluate the effect of sunitinib (sunitinib malate) compared to placebo on progression-free survival (PFS) in advanced non-small cell lung cancer (NSCLC) patients who have had either stable or responding disease over the course of their initial 4 cycles of platinum-based therapy. SECONDARY OBJECTIVES: I. To evaluate the toxicity of sunitinib compared to placebo in the maintenance setting. II. To evaluate the additional response rate as a result of sunitinib in this setting. III. To assess the impact of sunitinib on overall survival compared to the placebo arm. IV. To assess the impact of sunitinib on delaying the time to deterioration in quality of life and symptom progression compared to placebo using the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) and Lung Cancer Module (LC13). V. To assess vascular endothelial growth factor (VEGF) haplotypes in advanced non-small cell lung cancer and sunitinib maintenance. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive sunitinib malate orally (PO) once daily (QD) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive placebo PO QD 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 up every 3 months for 1 year, every 6 months for 1 year, and then periodically for 3 years.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
Condition ICMJE	Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer
Intervention ICMJE	Other: Laboratory Biomarker Analysis Correlative studies; Other: Placebo Given PO Other Names: placebo therapy PLCB sham therapy; Other: Quality-of-Life Assessment Ancillary studies Other Name: Quality of Life Assessment; Drug: Sunitinib Malate Given PO Other Names: SU011248 SU11248 sunitinib Sutent
Study Arms	Experimental: Arm I (sunitinib malate) Patients receive sunitinib malate 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Interventions: Other: Laboratory Biomarker Analysis Other: Quality-of-Life Assessment Drug: Sunitinib Malate; Placebo Comparator: Arm II (placebo) Patients receive placebo 37.5 mg PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Interventions: Other: Laboratory Biomarker Analysis Other: Placebo Other: Quality-of-Life Assessment
Publications *	Baggstrom MQ, Socinski MA, Wang XF, Gu L, Stinchcombe TE, Edelman MJ, Baker S Jr, Feliciano J, Novotny P, Hahn O, Crawford JA, Vokes EE. Maintenance Sunitinib following Initial Platinum-Based Combination Chemotherapy in Advanced-Stage IIIB/IV Non-Small Cell Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Phase III Study-CALGB 30607 (Alliance). J Thorac Oncol. 2017 May;12(5):843-849. doi: 10.1016/j.jtho.2017.01.022. Epub 2017 Feb 1.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: June 26, 2015)	210
Original Enrollment ICMJE; (submitted: June 6, 2008)	156
Actual Study Completion Date	May 2015
Actual Primary Completion Date	November 2013 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Histologic or cytologic documentation of primary non-small cell lung cancer; 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 central nervous system (CNS) metastases must be asymptomatic, must have 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; 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; patients will be registered 3-5 weeks following day 1 of cycle 4 of prior therapy; 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 Measurable disease: lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 2 cm with conventional techniques or as >= 1 cm with spiral computed tomography (CT) scan Non-measurable disease: all other lesions, including small lesions (longest diameter < 20 mm with conventional techniques or < 10 mm with spiral CT scan) and truly non-measurable lesions; lesions that are considered non-measurable include 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; Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; Non-pregnant and non-nursing; No ongoing cardiac dysrhythmias, atrial fibrillation, or history of corrected QT (QTc) interval >= 500 msec (within 2 years prior to registration); the use of agents with proarrhythmic potential (e.g., quinidine, procainamide, disopyramide, sotalol, probucol, haloperidol, risperidone, indapamide, flecainide) is not recommended while on protocol therapy; Patients with class I New York Heart Association (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 III 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, pulmonary embolism, 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 following inhibitors of cytochrome P450 3A4 (CYP3A4) are prohibited within 7 days before beginning and during treatment with sunitinib: azole antifungals (ketoconazole, itraconazole), diltiazem, clarithromycin, erythromycin, verapamil, delavirdine, and human immunodeficiency virus [HIV] protease inhibitors (indinavir, saquinavir, ritonavir, atazanavir, nelfinavir); the following inducers of CYP3A4 are prohibited within 12 days before beginning and during treatment with sunitinib: rifampin, rifabutin, carbamazepine, phenobarbital, phenytoin, St. John's Wort, efavirenz, tipranavir; other inhibitors and inducers of CYP3A4 may be used if necessary, but their use is discouraged; Patients unable to take oral medication are not eligible; Granulocytes >= 1,500/mcl; Platelet count >= 100,000/mcl; Total bilirubin =< 1.5 x upper limit of normal (ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)=< 2.5 x ULN; patients with liver metastases may have AST and ALT =< 5 x ULN; all other patients will have AST and ALT =< 2.5 x ULN; Creatinine =< 1.5 mg/dl
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00693992
Other Study ID Numbers ICMJE	NCI-2009-00469; NCI-2009-00469 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); CDR0000597649; CALGB 30607 ( Other Identifier: Alliance for Clinical Trials in Oncology ); CALGB-30607 ( Other Identifier: CTEP ); U10CA180821 ( U.S. NIH Grant/Contract ); U10CA031946 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	National Cancer Institute (NCI)
Study Sponsor ICMJE	National Cancer Institute (NCI)
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Mark Socinski Alliance for Clinical Trials in Oncology
PRS Account	National Cancer Institute (NCI)
Verification Date	July 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP