NGR015: Study in Second Line for Patient With Advanced Malignant Pleural Mesothelioma Pretreated With Pemetrexed
Condition: Malignant Pleural Mesothelioma
MeSH terms: Mesothelioma; Mesothelioma, Malignant
Intervention: NGR-hTNF plus Best Investigator's Choice (BIC); Placebo plus Best Investigator's Choice (BIC)
Intervention description: NGR-hTNF: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.
Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:
Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks); Placebo: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.
Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:
Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 400.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MPM; NGR-hTNF; NGR-hTNF plus BIC; Randomized double-blind phase III study

Summary:

      The main objective of the trial is to document the efficacy of NGR-hTNF administered at low
      dose weekly in advanced Malignant Pleural Mesothelioma patients previously treated with a
      pemetrexed-based chemotherapy regimen.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥ 18 years

          -  Histologically or cytological confirmed malignant pleural mesothelioma of any of the
             following subtype: epithelial, sarcomatoid, mixed, or unknown

          -  Prior treatment with no more than one systemic pemetrexed-based chemotherapy regimen
             administered for advanced or metastatic disease. Prior use of a biological agent in
             combination with a pemetrexed-based regimen and prior administration of intrapleural
             cytotoxic agents are allowed. Patients who have previously received anthracyclines
             should not receive doxorubicin

          -  ECOG Performance Status 0 - 2

          -  Life expectancy of ≥ 12 weeks

          -  Adequate baseline bone marrow, hepatic and renal function, defined as follows:

               1. Neutrophils ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L; hemoglobin ≥ 9 g/dL

               2. Bilirubin ≤ 1.5 x ULN

               3. AST and/or ALT ≤ 2.5 x ULN in absence of liver metastasis or ≤ 5 x ULN in
                  presence of liver metastasis

               4. Serum creatinine < 1.5 x ULN

          -  Measurable or non-measurable disease according to MPM-modified RECIST criteria

          -  Patients may have had prior therapy providing the following conditions are met:

               1. Surgery: wash-out period of 14 days

               2. Systemic and radiation anti-tumor therapy: wash-out period of 28 days

          -  Patients must give written informed consent to participate in the study

        Exclusion Criteria:

          -  Patients must not receive any other investigational agents while on study

          -  Patients with myocardial infarction within the last six months, unstable angina, New
             York Heart Association (NYHA) grade II or greater congestive heart failure, or serious
             cardiac arrhythmia requiring medication

          -  Uncontrolled hypertension

          -  QTc interval (congenital or acquired) > 450 ms

          -  History or evidence upon physical examination of CNS disease unless adequately treated
             (e.g., primary brain tumor, any brain metastasis, seizure not controlled with standard
             medical therapy, or history of stroke)

          -  Patients with active or uncontrolled systemic disease/infections or with serious
             illness or medical conditions, which is incompatible with the protocol

          -  Known hypersensitivity/allergic reaction to human albumin preparations or to any of
             the excipients

          -  Any psychological, familial, sociological or geographical condition potentially
             hampering compliance with the study protocol

          -  Pregnancy or lactation