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Chemotherapy With or Without Bevacizumab in Patients With Completely Resected Stage IB-IIIA Non-small Cell Lung Cancer

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

May 10, 2006
May 11, 2006
January 12, 2018
February 14, 2018
February 14, 2018
June 1, 2007
October 20, 2015   (Final data collection date for primary outcome measure)
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.
Not Provided
Complete list of historical versions of study NCT00324805 on ClinicalTrials.gov Archive Site
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.
Not Provided
  • 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 ]
Not Provided
 
Chemotherapy With or Without Bevacizumab in Patients With Completely Resected Stage IB-IIIA Non-small Cell Lung Cancer
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.

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 STUDIES:

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.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
    Given IV
    Other Names:
    • Anti-VEGF Humanized Monoclonal Antibody
    • Anti-VEGF rhuMAb
    • Avastin
    • Bevacizumab Biosimilar BEVZ92
    • Bevacizumab Biosimilar BI 695502
    • Bevacizumab Biosimilar CBT 124
    • Bevacizumab Biosimilar FKB238
    • Recombinant Humanized Anti-VEGF Monoclonal Antibody
    • rhuMab-VEGF
  • Drug: Cisplatin
    Given IV
    Other Names:
    • Abiplatin
    • Blastolem
    • Briplatin
    • Cis-diammine-dichloroplatinum
    • Cis-platinum II
    • Cismaplat
    • Cisplatina
    • Cisplatinum
    • Cisplatyl
    • Citosin
    • Cysplatyna
    • diamminedichloroplatinum (DDP)
    • Lederplatin
    • Metaplatin
    • Neoplatin
    • Peyrone's Chloride
    • Placis
    • Plastistil
    • Platamine
    • Platiblastin
    • Platinex
    • Platinol
    • Platinoxan
    • Platiran
    • Platistin
    • Platosin
  • Drug: Docetaxel
    Given IV
    Other Names:
    • Docecad
    • RP56976
    • Taxotere
    • Taxotere Injection Concentrate
  • Drug: Gemcitabine Hydrochloride
    Given IV
    Other Names:
    • dFdCyd
    • Difluorodeoxycytidine Hydrochloride
    • Gemzar
    • LY-188011
  • Drug: Pemetrexed Disodium
    Given IV
    Other Names:
    • Alimta
    • LY231514
  • Drug: Vinorelbine
    Given IV
    Other Names:
    • Biovelbin
    • Eunades
    • KW-2307
    • Navelbine
    • Navelbine Ditartrate
    • NVB
    • Vinorelbine Ditartrate
  • 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
    • Drug: Pemetrexed Disodium
    • Drug: Vinorelbine
  • 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
    • Drug: Pemetrexed Disodium
    • Drug: Vinorelbine
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
1501
Not Provided
October 16, 2023
October 20, 2015   (Final data collection date for primary outcome measure)

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
  • 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
  • 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
  • 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
  • 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 other 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 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:

    • 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

Exclusion Criteria:

  • 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
  • Having received any of the following:

    • Prior systemic chemotherapy at any time, but 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 and 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)
  • Any history of cerebral vascular accident (CVA) or transient ischemic attack (TIA)
  • Women who are 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
  • 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
  • History of bleeding diathesis or coagulopathy
  • Treatment with dipyridamole (Persantine), ticlopine (Ticlid), clopidogrel (Plavix) and/or cilostazol (Pletal); patients must have stopped taking any of these agents at least 7 days prior to randomization
  • Serious non-healing wound, ulcer, bone fracture, or having 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
  • History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to randomization
  • Any anticipated major surgical procedure(s) during the course of the study
  • Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • Ongoing post-operative hemoptysis (defined as bright red blood of 1/2 teaspoon or more)
  • Squamous cell histology for patients who will receive pemetrexed (pemetrexed disodium)/cisplatin therapy
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Canada,   Ireland,   Peru,   South Africa,   United States
 
 
NCT00324805
NCI-2009-00509
NCI-2009-00509 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000475774 ( Registry Identifier: Clinical Data Repository )
E1505 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
E1505 ( Other Identifier: CTEP )
U10CA180820 ( U.S. NIH Grant/Contract )
U10CA021115 ( U.S. NIH Grant/Contract )
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: Yes
Plan Description: Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.
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
Principal Investigator: Heather Wakelee ECOG-ACRIN Cancer Research Group
National Cancer Institute (NCI)
February 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP