|May 10, 2006
|January 12, 2017
|January 2018 (final data collection date for primary outcome measure)
|Overall survival [ Time Frame: Time from randomization to death, assessed up to 10 years ] [ Designated as safety issue: No ]
The primary comparison will be an intent-to-treat analysis including all randomized patients. The study design incorporates a group sequential testing plan using a truncated O'Brien-Fleming boundary function at an overall one-sided significance level of 0.025 for assessing the stratified logrank test at each interim analysis.
|Complete list of historical versions of study NCT00324805 on ClinicalTrials.gov Archive Site
- Disease-free survival (DFS) [ Time Frame: Time from randomization to an event (recurrence, new primary of lung cancer, or death), assessed up to 10 years ] [ Designated as safety issue: No ]
Intent to treat analysis per randomization will be conducted. Kaplan-Meier estimates of DFS will be calculated. The comparison will be assessed by using stratified log-rank test.
- Expression of intracellular adhesion molecule (ICAM) [ Time Frame: Up to 3 months after completion of study treatment ] [ Designated as safety issue: No ]
A stratified log-rank test will be used to assess whether the difference in the expression of ICAM predict survival at each time point. In addition, a Cox regression model will be fit to further determine how ICAM expression levels predict survival outcome controlling for other important covariates such as treatment type, age, gender, stage, performance status, and smoking status at each time point.
- Expression of vascular endothelial growth factor (VEGF) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
A stratified log-rank test will be used to assess whether the difference in the expression of VEGF predict survival at each time point. In addition, a Cox regression model will be fit to further determine how VEGF expression levels predict survival outcome controlling for other important covariates such as treatment type, age, gender, stage, performance status, and smoking status at each time point.
- Toxicity rates as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 1 year post-treatment ] [ Designated as safety issue: Yes ]
If the difference in the rate of a particular category of toxicities between the 2 arms (N=750 per arm) is at least 5% (4% vs. 9%), 96% power can be attained assuming a significance level of 5% (two-sided Chi Square test) and that the lower toxicity rate for one arm is 4%. A difference in the rates of grade 3-5 arterial thromboembolic events and bleeding events will be monitored and assessed between the treatment arms.
|Chemotherapy With or Without Bevacizumab in Treating Patients With Stage IB, Stage II, or Stage IIIA Non-small Cell Lung Cancer That Was Removed By Surgery
|A Phase III Randomized Trial of Adjuvant Chemotherapy With or Without Bevacizumab for Patients With Completely Resected Stage IB (≥ 4 cm) - IIIA Non-small Cell Lung Cancer (NSCLC)
|This randomized phase III trial studies chemotherapy and bevacizumab to see how well they work compared to chemotherapy alone in treating patients with stage IB, stage II, or stage IIIA non-small cell lung cancer that was removed by surgery. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab also may stop the growth of non-small cell lung cancer by blocking the growth of new blood vessels necessary for tumor growth. It is not yet known whether chemotherapy is more effective with or without bevacizumab in treating non-small cell lung cancer.
I. To evaluate overall survival with chemotherapy with or without bevacizumab used in the adjuvant setting in patients with resected stage IB (>= 4 cm) - IIIA non-small cell lung cancer (NSCLC).
I. To evaluate disease-free survival and toxicity with chemotherapy with or without bevacizumab used in the adjuvant setting in patients with resected stage IB (>= 4 cm) - IIIA NSCLC.
II. To perform analyses of tissue and blood to establish factors that predict clinical outcome in patients receiving chemotherapy, with or without bevacizumab, for resected early stage NSCLC.
III. To determine whether smoking status is linked to outcome for patients with resected stage IB (>= 4 cm) - IIIA NSCLC treated with chemotherapy with or without bevacizumab in the adjuvant setting.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I (adjuvant chemotherapy without bevacizumab): Patients receive 1 of 4 chemotherapy regimens.
REGIMEN 1: Patients receive vinorelbine ditartrate intravenously (IV) over 10 minutes on days 1 and 8 and cisplatin IV over 60 minutes on day 1 immediately following vinorelbine ditartrate administration.
REGIMEN 2: Patients receive docetaxel IV over 1 hour on day 1 and cisplatin over 1 hour on day 1 immediately following docetaxel administration.
REGIMEN 3: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV over 60 minutes on day 1 immediately following gemcitabine administration.
REGIMEN 4 (non-squamous histology only): Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 1 hour on day 1 immediately following pemetrexed disodium administration.
In all regimens, treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
ARM II (adjuvant chemotherapy with bevacizumab): Patients receive chemotherapy as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment with bevacizumab repeats every 21 days for up to 1 year.
After completion of study treatment, patients are followed up periodically for 10 years.
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
- Stage IB Non-Small Cell Lung Carcinoma
- Stage IIA Non-Small Cell Lung Carcinoma
- Stage IIB Non-Small Cell Lung Carcinoma
- Stage IIIA Non-Small Cell Lung Cancer
- Biological: Bevacizumab
- Anti-VEGF Humanized Monoclonal Antibody
- Anti-VEGF rhuMAb
- Bevacizumab Biosimilar BEVZ92
- Bevacizumab Biosimilar BI 695502
- Bevacizumab Biosimilar FKB238
- Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer
- Recombinant Humanized Anti-VEGF Monoclonal Antibody
- Drug: Cisplatin
- Cis-diamminedichloro Platinum (II)
- Cis-dichloroammine Platinum (II)
- Cis-platinous Diamine Dichloride
- Cis-platinum II
- Cis-platinum II Diamine Dichloride
- Peyrone's Chloride
- Peyrone's Salt
- Platinol- AQ
- Platinol-AQ VHA Plus
- Platinum Diamminodichloride
- Drug: Docetaxel
- Taxotere Injection Concentrate
- Drug: Gemcitabine Hydrochloride
- Difluorodeoxycytidine Hydrochloride
- Other: Laboratory Biomarker Analysis
- Drug: Pemetrexed Disodium
- N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium Salt
- Other: Questionnaire Administration
- Drug: Vinorelbine Tartrate
- Navelbine Ditartrate
- Vinorelbine Ditartrate
|Active, not recruiting
|January 2018 (final data collection date for primary outcome measure)
- In order to be eligible for this trial, patients must have undergone complete resection of their non-small cell lung cancer (NSCLC) [stage IB (>= 4 cm)] - [IIIA (T2-3N0, T1-3N1, T1-3N2] prior to enrollment; accepted types of resection will consist of lobectomy, sleeve lobectomy, bi-lobectomy or pneumonectomy; resections by segmentectomy or wedge resection will not be accepted; mediastinal lymph node sampling at specified levels is required pre-operatively (mediastinoscopy) or intraoperatively (level 7 and 4 for right sided tumors or level 7 and 5 and/or 6 for left sided tumors)
- Patients must be no less than 6 weeks (42 days) and no more than 12 weeks (84 days) post-thoracotomy at the time of randomization and must be adequately recovered from surgery
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Patients must not have received the following:
- Prior systemic chemotherapy at any time; methotrexate (MTX) given in low doses for non-malignant conditions with last dose at least 2 weeks prior to date of registration will be allowed; other low dose chemotherapeutics for non-malignant conditions will be considered, but review by the study chair is required
- Hormonal cancer therapy or radiation therapy as prior cancer treatment within 5 years of randomization; (prior surgery, biologic therapy, hormonal therapy, or radiation therapy for a malignancy over 5 years prior to enrollment that is now considered cured is acceptable)
- Patients must not have any history of cancer within 5 years from randomization, with the exception of in-situ carcinoma of the cervix or completely resected non-melanoma skin cancer
- Absolute neutrophil count (ANC) >= 1500 mm^3
- Platelets >= 100,000/mm^3
Prothrombin time/international normalized ratio (INR) =< 1.5
- Or, if patient is on therapeutic anticoagulation, prothrombin time/INR =< 3.0
- Partial thromboplastin time (PTT) =< institutional upper limit of normal (ULN) OR, if patient is on therapeutic anticoagulation, PTT must be =< 1.5 x ULN
- Total bilirubin =< 1.5 mg/dL
- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) < 5 x upper limit of normal (ULN)
- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 5 x upper limit of normal (ULN)
- Serum creatinine =< 1.5 x institutional upper limit of normal (ULN)
- Urine protein should be screened by urine analysis for urine protein creatinine (UPC) ratio; for UPC ratio > 0.5, 24-hour urine protein must be obtained and the level must be < 1000 mg (1 g) for patient enrollment
- Patients with a known history of myocardial infarction or other evidence of arterial thrombotic disease (angina) will be allowed on study only if they have had no evidence of active disease for at least 12 months prior to randomization
- Patients with any history of cerebral vascular accident (CVA) or transient ischemic attack (TIA) will not be allowed on trial
Women must not be pregnant or breast-feeding
- All females of childbearing potential must have a blood or urine test within 2 weeks prior to randomization to rule out pregnancy
- Both fertile men and women must agree to use adequate contraceptive measures during study treatment and for at least 6 months after completion of bevacizumab
- Patients must not have any clinically significant ongoing, active or serious infection, symptomatic or uncontrolled congestive heart failure, symptomatic or uncontrolled cardiac arrhythmia or any other medical condition or psychiatric illness/social situations that would limit compliance with study requirements
- Patients must have no history of bleeding diathesis or coagulopathy
- All patients must have a documented blood pressure (BP) with systolic =< 150 and diastolic =< 90 within 28 days of registration; patients with known hypertension must be on a stable regimen of anti-hypertensive therapy
- Patients receiving daily treatment with aspirin or non-steroidal anti-inflammatory agents (NSAIDS) are eligible; treatment with dipyridamole (Persantine), ticlopine (Ticlid), clopidogrel (Plavix) and/or cilostazol (Pletal) is not allowed; patients must have stopped taking any of these agents at least 7 days prior to randomization
- Patients must not have serious non-healing wound, ulcer, bone fracture, or have undergone a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization OR core biopsy within 7 days prior to randomization
- Patients must not have a history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to randomization
- Patients must not have any anticipated major surgical procedure(s) during the course of the study
- Patients must not have known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
- Patients may be on a stable regimen of therapeutic anticoagulation or may be receiving prophylactic anticoagulation of venous access devices, provided that coagulation studies meet entry criteria above; caution must be exercised for patients requiring anticoagulation, including treatment with low dose heparin or low molecular weight heparin for deep vein thrombosis (DVT) prophylaxis while on study
- Patients with ongoing post-operative hemoptysis (defined as bright red blood of 1/2 teaspoon or more) are not eligible; patients with pre-operative hemoptysis that has resolved post-operatively are eligible
Patients who will receive pemetrexed (pemetrexed disodium)/cisplatin therapy must also meet the following criteria:
- Patients assigned to pemetrexed/cisplatin therapy must NOT have squamous cell histology
- Calculated creatinine clearance must be obtained within 2 weeks of randomization and calculated creatinine clearance (CrCl) must be >= 45 mL/min using the standard Cockcroft and Gault formula, or the measured glomerular filtration rate (GFR) using the appropriate radiolabeled method (chromium-labeled ethylenediaminetetraacetic acid [51-CrEDTA] or technetium 99m diethylenetriamine-pentaacetic acid [Tc99m-DTPA]) must be used to calculate CrCl
|18 Years and older (Adult, Senior)
|Contact information is only displayed when the study is recruiting subjects
|United States, Canada, Ireland, Peru, South Africa
|NCI-2009-00509, NCI-2009-00509, ECOG-E1505, E1505, CDR0000475774, E1505, E1505, U10CA180820, U10CA021115
|National Cancer Institute (NCI)
|National Cancer Institute (NCI)
- Cancer and Leukemia Group B
- NCIC Clinical Trials Group
- North Central Cancer Treatment Group
- Southwest Oncology Group
||ECOG-ACRIN Cancer Research Group
|National Cancer Institute (NCI)