Trial record 1 of 1 for:    ECOG E5508
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Bevacizumab or Pemetrexed Disodium Alone or In Combination After Induction Therapy in Treating Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by National Cancer Institute (NCI)
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01107626
First received: April 20, 2010
Last updated: December 5, 2012
Last verified: December 2012
  Purpose

RATIONALE: Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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 may also stop the growth of non-small cell lung cancer by blocking blood flow to the tumor. Pemetrexed disodium may stop the growth of tumor cells by blocking some enzymes needed for cell growth. It is not yet known whether giving bevacizumab or pemetrexed disodium alone or in combination is more effective in treating non-squamous non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying bevacizumab and pemetrexed disodium alone or in combination after induction therapy to see how well they work in treating patients with advanced non-squamous non-small cell lung cancer.


Condition Intervention Phase
Lung Cancer
Biological: bevacizumab
Drug: pemetrexed disodium
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase III Study of Maintenance Therapy With Bevacizumab, Pemetrexed, or a Combination of Bevacizumab and Pemetrexed Following Carboplatin, Paclitaxel and Bevacizumab for Advanced Non-Squamous NSCLC

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Designated as safety issue: No ]
  • Objective response as measured by RECIST [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]
  • Association between bevacizumab and pemetrexed disodium population pharmacokinetics [ Designated as safety issue: No ]
  • Association between proteomic profiles and ICAM, VEGF, and FGF-beta with the clinical outcomes (Closed as of 04/01/2010) [ Designated as safety issue: No ]

Estimated Enrollment: 1282
Study Start Date: August 2010
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive bevacizumab IV over 30-90 minutes on day 1
Biological: bevacizumab
Given IV
Experimental: Arm II
Patients receive pemetrexed IV over 10 minutes on days 1.
Drug: pemetrexed disodium
Given IV
Experimental: Arm III
Patients receive bevacizumab as in arm I and pemetrexed as in arm II.
Biological: bevacizumab
Given IV
Drug: pemetrexed disodium
Given IV

  Hide Detailed Description

Detailed Description:

OBJECTIVES:

Primary

  • To compare the overall survival (OS) of patients with advanced non-squamous non-small cell lung cancer (NSCLC) treated with maintenance therapy with bevacizumab vs pemetrexed disodium vs bevacizumab and pemetrexed disodium following induction therapy.

Secondary

  • To determine the response rate in patients treated with these regimens.
  • To evaluate the progression-free survival (PFS) of patients treated with these regimens.
  • To define the toxicity of these regimens in these patients.
  • To determine the frequency of polymorphisms in VEGF 3578 AA, 1154 AA, ABCB1 G2677TT/AA, and ERCC-118 TT in patients treated with induction therapy comprising paclitaxel, carboplatin and bevacizumab and determine the association between genotypes and response rate.
  • To determine the association between bevacizumab and pemetrexed disodium population pharmacokinetics and patient-specific covariate with bevacizumab or pemetrexed disodium toxicity.
  • To determine the frequency of TSER*3 polymorphisms in NSCLC and the association between TSER polymorphisms and benefit from pemetrexed disodium.
  • To evaluate TS and ERCC1 expression by RT-PCR and MTAP mutations in existing tumor specimens as a predictor of pemetrexed disodium response.
  • To evaluate polymorphisms within CYPs 2C8, 3A4, 3A5 and/or the UGT1A1 collectively or monogenically as markers for variation in efficacious and/or toxic response of individuals to treatment with taxanes.
  • To explore the association between proteomic profiles and ICAM, VEGF, and FGF-beta with the clinical outcomes of the study (OS, PFS, and response) (Closed as of 04/01/2010).
  • To evaluate the ability of FOX03a to predict first-line treatment outcome in non-squamous NSCLC.(Closed as of 04/01/2010)
  • To evaluate the ability of ADSS1 to predict outcome of pemetrexed maintenance treatment in non-squamous NSCLC.(Closed as of 04/01/2010)
  • To develop proteomic classifiers to identify patient populations that would benefit from bevacizumab or pemetrexed therapy.(Closed as of 04/01/2010)

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to gender (male vs female), stage of disease (IIIB-T4Nx [with nodule in ipsilateral lung lobe and not candidate for combined chemotherapy and radiation] and IV M1a vs IV M1b vs recurrent), best response to first-time therapy (complete response/partial response vs stable disease), and smoking status (never vs smoker).

  • Induction therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
  • Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Treatment begins within 6 weeks of the last day of induction chemotherapy administration.

    • Arm I: Patients receive bevacizumab IV over 30-90 minutes on day 1.
    • Arm II: Patients receive pemetrexed disodium IV over 10 minutes on day 1.
    • Arm III: Patients receive bevacizumab as in arm I and pemetrexed as in arm II. In all arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Some patients undergo blood sample collection at baseline and periodically during study for pharmacokinetics, protein biomarkers, proteomic profiling (closed as of 04/01/10), and other analyses.

After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 2-5 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Cytologically or histologically confirmed non-small cell lung cancer (NSCLC)

    • Predominant non-squamous histology

      • NSCLC not otherwise specified allowed
      • Mixed tumors are categorized by the predominant cell type
  • Must meet 1 of the following criteria:

    • Stage IV disease including M1a or M1b stages or recurrent disease
    • Stage IIIB (T4NX) disease with ipsilateral lung lobe allowed provided patients are not candidates for combined chemotherapy or radiotherapy
  • Measurable or non-measurable disease as defined by RECIST criteria
  • Patient must have an overall stable or better response after 4 courses of induction therapy
  • No cavitary lesions in the lungs
  • Patients with brain metastasis must have received local therapy to the brain and have no evidence of progression in the brain for at least 2 weeks from the time of completion of local therapy, prior to registration

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Leukocytes ≥ 3,000/mm^3
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Total bilirubin ≤ institutional upper limit of normal (ULN)
  • AST and ALT ≤ 3 times ULN
  • Creatinine ≤ institutional ULN OR creatinine clearance ≥ 60 mL/min
  • Urine protein:urine dipstick ≤ 0-1+ (if > 1+, urine protein creatinine ratio must be < 1)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must agree to abstain from sexual intercourse or to use adequate contraceptive methods during and for at least 6 months after completion of study therapy
  • No prior malignancy within the past 3 years except superficial melanoma, basal cell carcinoma, or carcinoma in situ
  • No major hemoptysis within the past 4 weeks
  • No uncontrolled intercurrent illness including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Serious cardiac arrhythmia
    • Psychiatric illness and/or social situations that would limit compliance with study requirements
  • Patients with hypertension must be adequately controlled (BP < 150/100 mm Hg) with appropriate anti-hypertensive therapy or diet
  • No history of arterial thrombotic events or major bleeding within the past 12 months
  • No significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within the past 6 months
  • No significant traumatic injury in the past 3 months
  • No clinically significant cardiovascular disease
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
  • No history of serious non-healing wounds, ulcers, or bone fractures

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 12 months since prior adjuvant chemotherapy
  • At least 2 weeks since prior radiotherapy
  • Patients must not have had any major surgery such as thoracotomy, laparotomy, craniotomy, or significant traumatic injury within 6 weeks prior to registration

    • Biopsy procedures and chest tube insertion are not considered major surgery for the purpose of this protocol
  • More than 7 days since a core biopsy
  • Concurrent therapeutic anti-coagulation allowed
  • No prior systemic chemotherapy for advanced stage lung cancer
  • No prior paclitaxel, pemetrexed disodium, or bevacizumab

    • Prior carboplatin allowed provided it was given as part of adjuvant chemotherapy
  • No concurrent anti-retroviral therapy in patients with HIV infection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01107626

  Show 434 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Principal Investigator: Suresh Ramalingam, MD Winship Cancer Institute of Emory University
  More Information

Additional Information:
No publications provided

Responsible Party: Robert L. Comis, ECOG Group Chair's Office
ClinicalTrials.gov Identifier: NCT01107626     History of Changes
Other Study ID Numbers: CDR0000666482, ECOG-E5508
Study First Received: April 20, 2010
Last Updated: December 5, 2012
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
recurrent non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
adenocarcinoma of the lung
bronchoalveolar cell lung cancer
large cell lung cancer

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
Pemetrexed
Bevacizumab
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Folic Acid Antagonists
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014