ATREUS - Phase II Study on the Activity of Trabectedin in Patients With Malignant Pleural Mesothelioma (MPM)

Inclusion Criteria:

1. Histologically proven unresectable MPM. In order to make a reproducible diagnosis, in particular regarding biphasic MPM, histology must derive from transthoracic biopsies (at least 3 representative samples) or from videothoracoscopy (at least 5 representative samples)
2. Age \>18 years
3. Performance status 0-1 (ECOG)
4. Measurable disease (CT-PET) according to RECIST criteria modified for malignant pleural mesothelioma
5. Not more than one previous chemotherapy course (consisting of pemetrexed plus platinum derivative), excluded adjuvant therapy if PFS \< 12 months
6. A minimum of 3 weeks since previous tumour directed therapy
7. Recovery from toxic effects of previous therapies to NCI CTC AE Grade 0-1
8. Patients who have received palliative radiation are eligible if \<30% of bone marrow was irradiated and normal haematological function was completely regained
9. Haematologic variables: haemoglobin ≥ 9 g/dL, Absolute neutrophil count (ANC) ≥ 1,500/μL and Platelet count ≥ 100,000/μL
10. Serum creatinine ≤1.5 mg/dL or creatinine clearance ≥ 30 mL/min
11. Creatinine phosphokinase (CPK) ≤ 2.5 ULN
12. Hepatic function variables: Total bilirubin ≤ ULN, Total alkaline phosphatase ≤ 2.5 ULN or if \> 2.5 ULN alkaline phosphatase liver fraction or GGT or 5' nucleotidase must be determined and ≤ ULN, AST (serum aspartate transaminase \[SGOT\]) and ALT (serum alaninetransaminase \[SGPT\]) must be ≤ 2.5 x ULN, Albumin ≥ 25 g/L
13. Signed informed consent
14. Adequate contraceptive methods for male patients whose partner is of childbearing age/potential, during the study and for three months after the end of treatment

Exclusion Criteria:

1. \- Radiotherapy with curative intent to thoracic wall (concomitant with or prior to chemotherapy)
2. \- Uncompensated diabetes mellitus or other condition absolutely contra-indicating dexamethasone (used as pre-medication)
3. \- Patients enrolled in other study with experimental drugs
4. \- Women of childbearing age/potential
5. \- Prior exposure to trabectedin
6. \- History of other malignancies (except basal cell carcinoma or cervical carcinoma in situ, adequately treated), unless in remission from 5 years or more and judged of negligible potential of relapse
7. \- Active viral hepatitis or chronic liver disease
8. \- Unstable cardiac condition, including congestive heart failure or angina pectoris, myocardial infarction within one year before enrolment, uncontrolled arterial hypertension or arrhythmias
9. \- Active major infection
10. \- Other serious concomitant illness
11. \- Brain / leptomeningeal involvement