Trial record 1 of 110 for:    30607
Previous Study | Return to List | Next Study

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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00693992
First received: June 6, 2008
Last updated: April 8, 2014
Last verified: January 2014
  Purpose

This randomized phase III trial is studying sunitinib malate to see how well it works when given as maintenance therapy compared with a placebo in treating patients with stage III or stage IV non-small cell lung cancer previously treated 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 blood flow to the tumor. It is not yet known whether sunitinib malate is more effective than a placebo in treating non-small cell lung cancer.


Condition Intervention Phase
Stage IIIB Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Drug: sunitinib malate
Other: placebo
Procedure: quality-of-life assessment
Other: laboratory biomarker analysis
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Randomized, Phase III, Double-Blind Placebo-Controlled Trial of Sunitinib (NSC #736511, IND #74019) 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: Time from the date of randomization of non-progressing patients following the first-line therapy to the date of disease progression or death of any cause, whichever comes first, assessed up to 5 years ] [ Designated as safety issue: No ]
    PFS will be characterized by the Kaplan-Meier method. PFS will be performed using the intent-to-treat principle, which included all randomized patients. The comparisons of treatment arms on PFS will be done using the stratified log ranked.


Secondary Outcome Measures:
  • Grade and type of toxicity as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Contingency tables will be used to summarize the frequency of toxicity by severity and treatment. For comparison of the frequency of toxic events, Cochran-Mantel- Haenszel test stratified by gender, performance status and weight loss will be used to take advantage of the trend effect between toxicity grades.

  • Response rate (RR) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Response rate and its 95% confidence interval will be estimated by treatment arm. The association of response rate will be tested by Fisher's exact test and will be modeled using the logistic regression with other prognostic factor eligible to enter the model.

  • Overall survival (OS) [ Time Frame: Time between randomization and death of all causes, assessed up to 5 years ] [ Designated as safety issue: No ]
    OS will be characterized by the Kaplan-Meier method. OS analysis will be conducted similarly to PFS analysis.

  • Time to quality of life or symptom deterioration as assessed by continuous QOL scores, including QLQ-C30 and LC13 subscales [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    The time of symptom progression will be computed for each patient. Similar to PFS and OS, the univariate analysis with log rank test will be used to evaluate the effect of the experimental arm and the multivariate analysis with Cox's proportional hazard model will be used to evaluate the effect of the experimental arm while adjusting for other baseline prognostic factors. The rate of symptom progression at 3 and 6 weeks will be estimated for each arm and their difference will be tested using Fisher's exact test.

  • Time to deterioration in quality of life (QOL) and symptom progression using the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 and LC13 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    The time of symptom progression will be computed for each patient. Similar to PFS and OS, the univariate analysis with log rank test will be used to evaluate the effect of the experimental arm and the multivariate analysis with Cox's proportional hazard model will be used to evaluate the effect of the experimental arm while adjusting for other baseline prognostic factors. The rate of symptom progression at 3 and 6 weeks will be estimated for each arm and their difference will be tested using Fisher's exact test.

  • VEGF levels and correlation with clinical outcomes, including RR, PFS, and OS. [ Time Frame: Up to 6 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 244
Study Start Date: June 2008
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (enzyme inhibitor therapy)
Patients receive sunitinib malate PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: sunitinib malate
Given PO
Other Names:
  • SU11248
  • sunitinib
  • Sutent
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: laboratory biomarker analysis
Correlative studies
Placebo Comparator: Arm II (placebo)
Patients receive placebo PO once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Other: placebo
Given PO
Other Name: PLCB
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: laboratory biomarker analysis
Correlative studies

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: 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 sunitinib malate orally (PO) once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive placebo PO 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 tomograpy (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, itraconozole), 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00693992

  Show 470 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Mark Socinski Cancer and Leukemia Group B
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00693992     History of Changes
Obsolete Identifiers: NCT01647087
Other Study ID Numbers: NCI-2009-00469, NCI-2009-00469, CALGB-30607, CDR0000597649, CALGB 30607, CALGB-30607, P30CA014236, U10CA031946
Study First Received: June 6, 2008
Last Updated: April 8, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Sunitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on April 20, 2014