Study of AVE0005 (VEGF Trap) in Locally Advanced or Metastatic Platinum- and Erlotinib- Resistant Non-small-cell-lung Adenocarcinoma
Condition: Pulmonary Diseases; Neoplasms, Lung
MeSH terms: Neoplasms; Adenocarcinoma; Adenocarcinoma of Lung; Lung Neoplasms
Intervention: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
Intervention description: Aflibercept 4.0 mg/kg administered intravenously (IV) over a period of at least 1 hour once every 2 weeks.
Aflibercept could be reduced by 1 dose level (to 3.0 mg/kg) or 2 dose levels (to 2.0 mg/kg) in case of uncontrolled hypertension or urinary protein >3.5 g/24 hours. Intrapatient dose escalation was not to be permitted. Participants requiring more than 2 dose level reductions would be withdrawn from study treatment.
Intervention MeSH terms: Aflibercept
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 98.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: lung; cancer; non-small-cell lung cancer; metastatic; carcinoma; lung neoplasm; lung diseases; angiogenesis; anti-angiogenesis; anti-angiogenesis inhibitors; cancer and other neoplasms; respiratory tract; (lung and bronchial) diseases

Summary:

      This study evaluated the efficacy and safety of aflibercept in the treatment of participants
      with advanced chemoresistant non-small cell lung adenocarcinoma (NSCLA).

      Primary objective:

        -  To determine the overall objective response rate (ORR) of AVE0005 (ziv-aflibercept,
           aflibercept, VEGF trap, ZALTRAP®) 4.0 mg/kg intravenously (IV) every 2 weeks in
           participants with platinum- and erlotinib-resistant, locally advanced or metastatic
           NSCLA.

      Secondary objective:

        -  To assess duration of response (DR), progression-free survival (PFS), and overall
           survival (OS) in this participant population

        -  To evaluate the safety profile of IV AVE0005 (ziv-aflibercept, aflibercept, VEGF trap,
           ZALTRAP®).

      This study employed an Independent Review Committee (IRC) for radiological tumor assessments.
      For all tumor assessment-related efficacy variables, two analyses were performed: the primary
      analysis was based on Independent Review Committee (IRC) reviewed data and the secondary
      analysis was based on Investigator evaluation.

      In addition, both Response Evaluation Criteria In Solid Tumors (RECIST) and Modified Response
      Evaluation Criteria In Solid Tumors (mRECIST) were used to assess tumors. Where as RECIST
      criteria only consider the longest diameter of the tumors for calculations pertaining to
      changes in tumor size, mRECIST assessments also account for the differences in the cavities
      of lesions observed in non-small-cell lung cancer (NSCLC). Responses based on RECIST and
      mRECIST are reported.
    

Eligibility criteria:

        Participants who met the following criteria were eligible for the study.

        Inclusion Criteria:

          -  Histologically confirmed non-small-cell lung adenocarcinoma that is locally advanced
             or metastatic

          -  Prior treatment with at least 2 cancer drug regimens in the advanced disease setting

          -  Platinum- and erlotinib-resistant disease defined by relapse or progression during or
             after treatment

          -  Measurable disease by RECIST criteria

          -  ECOG Performance status less than or equal to 2

          -  Resolution of any toxic effects of prior therapy

          -  Adequate organ and bone marrow function

          -  Female patients must be post-menopausal, surgically sterile or using effective
             contraception

          -  Willing and able to comply with study procedures and sign informed consent

        Exclusion Criteria:

          -  Diagnosis of squamous-cell lung cancer or any second malignancy within the last 5
             years (except for adequately treated basal cell or squamous cell skin cancer or in
             situ carcinoma of the cervix uteri)

          -  Prior treatment with a VEGF or VEGF receptor inhibitor with the exception of
             bevacizumab (Avastin-TM)

          -  Anticipation of a need for major surgical procedure

          -  Treatment with chemotherapy, radiotherapy, surgery, blood products, or an
             investigational agent within 3 weeks (6 weeks for nitrosoureas, mitomycin C,
             immunotherapy, or cytokine therapy) of study enrollment

          -  Uncontrolled hypertension

          -  Any severe or acute medical or psychiatric problem within the past 6 months requiring
             further investigation or that may cause undue risk for the patient's safety

          -  History of brain metastases, spinal cord compression, or carcinomatous meningitis, or
             new evidence of brain or leptomeningeal disease

          -  Active infection or on antiretroviral therapy for HIV disease

          -  Pregnant or breast-feeding

        The above information is not intended to contain all considerations relevant to potential
        participation in a clinical trial.