Trial record 1 of 1 for:    E1505
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Chemotherapy With or Without Bevacizumab in Treating Patients With Stage IB, Stage II, or Stage IIIA Non-Small Lung Cancer That Was Removed By Surgery

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Southwest Oncology Group (SWOG) Research Base
North Central Cancer Treatment Group
Cancer and Leukemia Group B
NCIC Clinical Trials Group
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00324805
First received: May 10, 2006
Last updated: March 26, 2014
Last verified: December 2013
  Purpose

This randomized phase III trial is studying 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 or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab also may stop the growth of tumor cells by blocking blood flow to the tumor. Giving chemotherapy together with bevacizumab after surgery may kill any tumor cells that remain after surgery. It is not yet known whether chemotherapy is more effective with or without bevacizumab in treating non-small cell lung cancer.


Condition Intervention Phase
Stage IB Non-small Cell Lung Cancer
Stage IIA Non-small Cell Lung Cancer
Stage IIB Non-small Cell Lung Cancer
Stage IIIA Non-small Cell Lung Cancer
Drug: gemcitabine hydrochloride
Drug: vinorelbine tartrate
Drug: cisplatin
Drug: docetaxel
Drug: pemetrexed disodium
Biological: bevacizumab
Other: questionnaire administration
Other: laboratory biomarker analysis
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Randomized Trial of Adjuvant Chemotherapy With or Without Bevacizumab for Patients With Completely Resected Stage IB (> 4cm)-IIIA Non-Small Lung Cancer (NSCLC)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Overall survival (OS) [ 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. The O'Brien-Fleming group sequential boundary adjusts for the sequential testing and the use function methodology of Lan and DeMets 1 will be employed to adjust the boundaries if the actual interim analyses do not correspond with the projected information times provided.


Secondary Outcome Measures:
  • Disease-free survival (DFS) [ Time Frame: Time from randomization to an event, 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 calculated3. The comparison will be assessed by using stratified log-rank test.

  • Toxicity as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) 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 (ATE) and bleeding events will be monitored and assessed between the treatment arms.

  • Correlation between VEGF and ICAM expression and clinical outcomes (OS and DFS) by gene expression analysis and immunohistochemistry [ Time Frame: From baseline to up to 15 months ] [ Designated as safety issue: No ]
    Stratified log-rank test to assess whether the difference in the expression level of VEGF/ICAM predict survival at each time-point will be used. A Cox regression model to further determine how VEGF/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. Longitudinal techniques will be used to assess whether the ICAM expression levels in the blood differ in the two treatment arms over time

  • Correlation between smoking status and OS assessed by the Smoking Status Survey [ Time Frame: From baseline to up to 1 year ] [ Designated as safety issue: No ]
    Descriptive and summary statistics will be conducted on the smoking questionnaire data.


Estimated Enrollment: 1500
Study Start Date: June 2007
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (chemotherapy)
Patients receive one of the following: 1) vinorelbine ditartrate IV over 10 minutes on days 1 and 8 and cisplatin IV over 1 hour on day 1, 2) docetaxel IV over 1 hour and cisplatin IV over 1 hour on day 1, 3) gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV over 1 hour on day 1, or 4) pemetrexed disodium IV over 10 minutes and cisplatin IV over 1 hour on day 1. Treatment repeats every 3 weeks for up to 4 courses.
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Drug: vinorelbine tartrate
Given IV
Other Names:
  • Eunades
  • navelbine ditartrate
  • NVB
  • VNB
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Drug: pemetrexed disodium
Given IV
Other Names:
  • ALIMTA
  • LY231514
  • MTA
Other: questionnaire administration
Ancillary studies
Other: laboratory biomarker analysis
Correlatives studies
Experimental: Arm II (chemotherapy, monoclonal antibody therapy)
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.
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Drug: vinorelbine tartrate
Given IV
Other Names:
  • Eunades
  • navelbine ditartrate
  • NVB
  • VNB
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Drug: pemetrexed disodium
Given IV
Other Names:
  • ALIMTA
  • LY231514
  • MTA
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Other: questionnaire administration
Ancillary studies
Other: laboratory biomarker analysis
Correlatives studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Compare overall survival of patients with completely resected stage IB (tumors ≥ 4cm)-IIIA non-small cell lung cancer treated with adjuvant chemotherapy with or without bevacizumab.

SECONDARY OBJECTIVES:

I. Compare disease-free survival of patients treated with these regimens. II. Compare the toxicity of these regimens in these patients. III. Perform analyses of tissue and blood to establish factors that predict clinical outcome in patients treated with these regimens.

IV. Determine whether smoking status is linked to outcome in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to type of chemotherapy (cisplatin/vinorelbine ditartrate vs cisplatin/docetaxel vs cisplatin/gemcitabine hydrochloride vs cisplatin/pemetrexed disodium), stage (IB vs II vs IIIA [N2] vs IIIA [T3, N1]), histology (squamous cell vs other), and gender. 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 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. Patients complete smoking status questionnaires at baseline and then every 3 months during study treatment.

After completion of study treatment, patients are followed periodically for 10 years.

  Eligibility

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

Inclusion Criteria:

  • Diagnosis of stage IB-IIIA (T2-3 N0, T1-3 N1, T1-3 N3) non-small cell lung cancer (NSCLC)

    • Patients with stage IB disease must have tumors measuring ≥ 4 cm
  • No non-squamous cell histology (for patient assigned to receive the pemetrexed disodium and cisplatin therapy)
  • Must have undergone complete resection of NSCLC within the past 6-12 weeks

    • Accepted types of resection include any of the following:

      • Lobectomy
      • Sleeve lobectomy
      • Bilobectomy
      • Pneumonectomy
    • No resection by segmentectomy or wedge resection
  • Mediastinal lymph node sampling at specific levels is required pre-operatively (mediastinoscopy) or intraoperatively (level 7 for right-sided tumors or level 7 and 5 and/or 6 for left sided tumors)
  • ECOG performance status 0-1
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • INR ≤ 1.5 OR INR ≤ 3.0 with therapeutic anticoagulation
  • PTT normal OR PTT ≤ 1.5 times upper limit of normal (ULN) for patients on therapeutic anticoagulation
  • Bilirubin ≤ 1.5 mg/dL
  • AST and ALT < 5 times ULN
  • Creatinine ≤ 1.5 times ULN
  • Creatinine clearance ≥ 45 mL/min (for patient assigned to receive the pemetrexed disodium and cisplatin therapy)
  • If urine protein: creatinine ratio > 0.5, then urine protein must be < 1,000 mg by 24-hour urine collection
  • No other cancer within the past 5 years except in situ carcinoma of the cervix or completely resected nonmelanoma skin cancer
  • Known history of myocardial infarction or other evidence of arterial thrombotic disease (angina) allowed if there is no evidence of active disease within the past 12 months
  • No history of cerebrovascular accident or transient ischemic attack
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for at least 6 months after completion of study treatment
  • No clinically significant ongoing, active, or serious infection, symptomatic or uncontrolled congestive heart failure or cardiac arrhythmia, psychiatric illness or social situation, or any other medical condition that would preclude study compliance
  • No history of bleeding diathesis or coagulopathy
  • Systolic blood pressure (BP) ≤ 150 and diastolic BP ≤ 90 within the past 28days

    • Patients with known hypertension on a stable regimen of antihypertensive therapy allowed
  • No serious nonhealing wound, ulcer, or bone fracture
  • No significant traumatic injury within the past 28 days
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
  • No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • No ongoing postoperative hemoptysis (i.e., bright red blood of ≥ ½ teaspoon
  • Recovered from prior surgery
  • At least 7 days since prior aspirin or non-steroidal anti-inflammatory agents (NSAIDS), dipyridamole (Persantine), ticlopine (Ticlid),clopidogrel (Plavix) and/or cilostazol (Pletal)
  • No prior systemic chemotherapy

    • Prior methotrexate given in low doses for non-malignant conditions with the last dose ≥ 2 weeks ago is allowed
    • Other low-dose chemotherapeutics for non-malignant conditions may be allowed after review by the study chair
  • No hormonal cancer therapy or radiotherapy as cancer treatment within the past 5years

    • Prior surgery, biologic therapy, hormonal therapy, or radiotherapy for a malignancy diagnosed > 5 years prior to study entry that is now considered cured allowed
  • No major surgery or open biopsy within the past 28 days

    • No anticipated major surgery during course of treatment
  • No core biopsy within the past 7 days
  • Concurrent therapeutic anticoagulation therapy allowed
  • No concurrent aminoglycoside antibiotics
  • No concurrent growth factors
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00324805

  Show 1123 Study Locations
Sponsors and Collaborators
Southwest Oncology Group (SWOG) Research Base
North Central Cancer Treatment Group
Cancer and Leukemia Group B
NCIC Clinical Trials Group
Investigators
Principal Investigator: Heather Wakelee Eastern Cooperative Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00324805     History of Changes
Other Study ID Numbers: NCI-2009-00509, NCI-2009-00509, ECOG-E1505, CDR0000475774, E1505, E1505, U10CA021115
Study First Received: May 10, 2006
Last Updated: March 26, 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
Antibodies
Antibodies, Monoclonal
Gemcitabine
Vinorelbine
Docetaxel
Pemetrexed
Bevacizumab
Cisplatin
Vinblastine
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on April 15, 2014