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

• ClinicalTrials.gov Identifier: NCT00324805
• Recruitment Status: Active, not recruiting
• First Posted: May 11, 2006
• Results First Posted: February 14, 2018
• Last Update Posted: April 17, 2024
• Sponsor: National Cancer Institute (NCI)
• Collaborators: Cancer and Leukemia Group B; NCIC Clinical Trials Group; North Central Cancer Treatment Group; SWOG Cancer Research Network
• Information provided by (Responsible Party): National Cancer Institute (NCI)

Tracking Information

• First Submitted Date: May 10, 2006
• First Posted Date: May 11, 2006
• Results First Submitted Date: January 12, 2018
• Results First Posted Date: February 14, 2018
• Last Update Posted Date: April 17, 2024
• Actual Study Start Date: June 1, 2007
• Actual Primary Completion Date: October 20, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 12, 2018)

Overall Survival [ Time Frame: From registration to death, up to 10 years ]

Overall survival (OS) was defined as the time from randomization to death from any cause, and patients who were thought to be alive at the time of final analysis were censored at the last date of contact. The study failed to meet its primary endpoint.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: February 12, 2018)

Disease-free Survival [ Time Frame: From registration to death, up to 10 years ]

Disease-free survival (DFS) was defined as the time from randomization to an event. Events include disease recurrence, new primary of lung cancer, second primaries or death, whichever occurred first; however, it should be noted that patients with new primaries at other non-lung sites should have continued followup for recurrence of the original cancer. Patients that have not had an event reported at analysis were censored at their last date of disease assessment.

• Original Secondary Outcome Measures: Not Provided

Current Other Pre-specified Outcome Measures (submitted: February 12, 2018)

• 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 ]
  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.
• Perform Analyses of Tissue and Blood to Establish Factors That Predict for Clinical Outcome in Patients Receiving Chemotherapy, With or Without Bevacizumab, for Resected Early Stage NSCLC. [ Time Frame: From registration to death, up to 10 years ]
• To Determine Whether Smoking Status is Linked to Outcome for Patients With Resected Stage IB - IIIA NSCLC Treated With Chemotherapy With or Without Bevacizumab in the Adjuvant Setting. [ Time Frame: From registration to death, up to 10 years ]

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: 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)
• Brief Summary: 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.

Detailed Description

PRIMARY OBJECTIVES:

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).

SECONDARY OBJECTIVES:

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.

CORRELATIVE OBJECTIVES:

I. 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.

II. 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Stage IB Lung Non-Small Cell Carcinoma AJCC v7
• Stage IIA Lung Non-Small Cell Carcinoma AJCC v7
• Stage IIB Lung Non-Small Cell Carcinoma AJCC v7
• Stage IIIA Lung Non-Small Cell Cancer AJCC v7

Intervention

• Biological: Bevacizumab
  Given IV
  Other Names:

  • ABP 215
  • Anti-VEGF
  • Anti-VEGF Humanized Monoclonal Antibody
  • Anti-VEGF Monoclonal Antibody SIBP04
  • Anti-VEGF rhuMAb
  • Avastin
  • BAT 1706
  • BAT-1706
  • BAT1706
  • BAT1706 Biosimilar
  • Bevacizumab awwb
  • Bevacizumab Biosimilar ABP 215
  • Bevacizumab Biosimilar BAT1706
  • Bevacizumab Biosimilar BEVZ92
  • Bevacizumab Biosimilar BI 695502
  • Bevacizumab Biosimilar CBT 124
  • Bevacizumab Biosimilar CT-P16
  • Bevacizumab Biosimilar FKB238
  • Bevacizumab Biosimilar GB-222
  • Bevacizumab Biosimilar HD204
  • Bevacizumab Biosimilar HLX04
  • Bevacizumab Biosimilar IBI305
  • Bevacizumab Biosimilar LY01008
  • Bevacizumab Biosimilar MIL60
  • Bevacizumab Biosimilar Mvasi
  • Bevacizumab Biosimilar MYL-1402O
  • Bevacizumab Biosimilar QL 1101
  • Bevacizumab Biosimilar QL1101
  • Bevacizumab Biosimilar RPH-001
  • Bevacizumab Biosimilar SCT501
  • Bevacizumab Biosimilar Zirabev
  • Bevacizumab-adcd
  • Bevacizumab-awwb
  • Bevacizumab-bvzr
  • BP102
  • BP102 Biosimilar
  • CT-P16
  • HD204
  • 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
  • Mvasi
  • MYL-1402O
  • QL1101
  • Recombinant Humanized Anti-VEGF Monoclonal Antibody
  • rhuMab-VEGF
  • SCT501
  • SIBP 04
  • SIBP-04
  • SIBP04
  • Vegzelma
  • Zirabev
• Drug: Cisplatin
  Given IV
  Other Names:

  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin
• Drug: Docetaxel
  Given IV
  Other Names:

  • Docecad
  • RP 56976
  • RP56976
  • Taxotere
  • Taxotere Injection Concentrate
• Drug: Gemcitabine Hydrochloride
  Given IV
  Other Names:

  • dFdCyd
  • Difluorodeoxycytidine Hydrochloride
  • Gemcitabine HCI
  • Gemzar
  • LY-188011
  • LY188011
• Other: Laboratory Biomarker Analysis
  Correlative studies
• Drug: Pemetrexed Disodium
  Given IV
  Other Names:

  • Alimta
  • Almita
  • LY231514
  • 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
  Ancillary studies
• Drug: Vinorelbine Tartrate
  Given IV
  Other Names:

  • Biovelbin
  • Eunades
  • KW-2307
  • Navelbine
  • Navelbine Ditartrate
  • NVB
  • Vinorelbine Ditartrate

Study Arms

• Active Comparator: Arm I (chemotherapy)

  Patients receive one of the following. For all, treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

  REGIMEN 1: Vinorelbine ditartrate 30 mg/m2 IV on days 1 and 8, cisplatin 75 mg/m2 IV over 60 minutes on day 1 REGIMEN 2: Docetaxel 75 mg/m2 IV and cisplastin 75 mg/m2 IV on day 1 REGIMEN 3: Gemcitabine hydrochloride 1200 mg/m2 IV on days 1 and 8, cisplatin 75 mg/m2 IV on day 1 REGIMEN 4 (non-squamous histology only): Pemetrexed disodium 500mg/m2 IV and cisplatin 75 mg/m2 IV on day 1

  Interventions:

  • Drug: Cisplatin
  • Drug: Docetaxel
  • Drug: Gemcitabine Hydrochloride
  • Other: Laboratory Biomarker Analysis
  • Drug: Pemetrexed Disodium
  • Other: Questionnaire Administration
  • Drug: Vinorelbine Tartrate
• Experimental: Arm II (chemotherapy, 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.
  Interventions:

  • Biological: Bevacizumab
  • Drug: Cisplatin
  • Drug: Docetaxel
  • Drug: Gemcitabine Hydrochloride
  • Other: Laboratory Biomarker Analysis
  • Drug: Pemetrexed Disodium
  • Other: Questionnaire Administration
  • Drug: Vinorelbine Tartrate

• Publications *: Wakelee HA, Dahlberg SE, Keller SM, Tester WJ, Gandara DR, Graziano SL, Adjei AA, Leighl NB, Aisner SC, Rothman JM, Patel JD, Sborov MD, McDermott SR, Perez-Soler R, Traynor AM, Butts C, Evans T, Shafqat A, Chapman AE, Kasbari SS, Horn L, Ramalingam SS, Schiller JH; ECOG-ACRIN. Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1610-1623. doi: 10.1016/S1470-2045(17)30691-5. Epub 2017 Nov 9.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 12, 2018): 1501
• Original Enrollment: Not Provided
• Estimated Study Completion Date: October 16, 2024
• Actual Primary Completion Date: October 20, 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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 ([51]chromium-labeled ethylenediaminetetraacetic acid [51-CrEDTA] or technetium 99m diethylenetriamine-pentaacetic acid [Tc99m-DTPA]) must be used to calculate CrCl

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Ireland, Peru, South Africa, United States

Administrative Information

• NCT Number: NCT00324805
• Other Study ID Numbers: NCI-2009-00509; NCI-2009-00509 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 09-0404; E1505; CDR0000475774; ECOG-E1505; E1505 ( Other Identifier: ECOG-ACRIN Cancer Research Group ); E1505 ( Other Identifier: CTEP ); U10CA180820 ( U.S. NIH Grant/Contract ); U10CA021115 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: National Cancer Institute (NCI)
• Original Responsible Party: Not Provided
• Current Study Sponsor: National Cancer Institute (NCI)
• Original Study Sponsor: Eastern Cooperative Oncology Group

Collaborators

• Cancer and Leukemia Group B
• NCIC Clinical Trials Group
• North Central Cancer Treatment Group
• SWOG Cancer Research Network

Investigators

• Principal Investigator: Heather A Wakelee; ECOG-ACRIN Cancer Research Group

• PRS Account: National Cancer Institute (NCI)
• Verification Date: April 2024