Phase II Anetumab Ravtansine as 2nd Line Treatment for Malignant Pleural Mesothelioma (MPM)
Condition: Mesothelioma
MeSH terms: Mesothelioma; Mesothelioma, Malignant
Intervention: Anetumab ravtansine (BAY94-9343); Vinorelbine
Intervention description: Starting dose: 6.5 mg/kg administered as IV infusion over 1 h every 3 weeks until disease progression or treatment withdrawal for any reason. Dose reductions are permitted.; Starting dose: 30mg/m^2 administered as an IV infusion over 6 to 10 min every week until disease progression or treatment withdrawal for any reason. Dose reductions are permitted per standard practise.
Intervention MeSH terms: Vinorelbine; Maytansine; Anetumab ravtansine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 248.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The main purpose of the 15743 study is to assess efficacy and safety of anetumab ravtansine
      versus vinorelbine in progression free survival in patients with stage IV mesothelin
      overexpressing malignant pleural mesothelioma (MPM).

      210 eligible patients will be randomized to receive either anetumab ravtansine every three
      weeks or weekly vinorelbine.

      Treatment will continue until centrally confirmed disease progression or until another
      criterion is met for withdrawal from the study. Patients will enter follow up phase to
      capture safety and endpoint data as required.

      Efficacy will be measured by evaluating progression free survival from randomization.
      Radiological tumor assessments will be performed at defined time points until the patient's
      disease progresses.

      Blood samples will be collected for safety, pharmacokinetic and biomarker analysis. Archival
      or fresh biopsy tissue may also be collected for central pathology review and biomarkers.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histological documentation of malignant pleural mesothelioma (MPM) overexpressing
             mesothelin

          -  Unresectable locally advanced or metastatic MPM after locally confirmed progression on
             1st line treatment with platinum in combination with pemetrexed.

          -  Patients must have measurable disease

          -  Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1

          -  Life expectancy of at least 3 months.

          -  Adequate bone marrow, liver and renal function

          -  Left ventricular ejection fraction (LVEF) ≥ 50% or the lower limit of normal (LLN)
             according to local institution ranges of normality.

        Exclusion Criteria:

          -  More than 1 previous systemic anti-cancer therapy line

          -  Patients with corneal epitheliopathy or any eye disorder that may predispose the
             patients to this condition at the discretion of the investigator in consultation with
             the ophthalmologist.

          -  Brain metastases, meningeal tumours or other metastases in the central nervous system

          -  Evidence of history of bleeding diathesis.

          -  Ongoing or active infection (bacterial, fungal, or viral) of National Cancer
             Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03
             Grade > 2.

          -  Pre-existing cardiac conditions