Efficacy and Safety of Plitidepsin in Patients With Advanced Unresectable or Metastatic, Relapsed/Refractory, Dedifferentiated Liposarcoma (DLPS): an Exploratory Phase II Multicenter Trial

Inclusion Criteria

• •1. Voluntarily signed and dated written informed consent prior to any study specific procedure.
• •2. Histologically confirmed DLPS by central review.
• •3. Metastatic or unresectable locally advanced disease
• •4. Progressive disease according to RECIST v1.1 criteria diagnosed on the basis of two CT scan obtained at an interval less than 3 months and confirmed by central review
• •5. At least one prior anthracycline-containing chemotherapy regimen
• •6. Age ≥ 18 years.
• •7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1.
• •8. Measurable disease according to RECIST v1.1 outside any previously irradiated field.
• •9. Adequate hematological, renal, metabolic and hepatic function.
• •1. Hemoglobin ≥ 9 g/dl (patients may have received prior red blood cell \[RBC\] transfusion, if clinically indicated); absolute neutrophil count (ANC) ≥ 1.2 x 109/l, and platelet count ≥ 100 x 109/l.
• •2. Alkaline phosphatase (AP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) 2.5 x upper limit of normality (ULN) (5 in case of extensive skeletal involvement for AP exclusively).
• •3. Total bilirubin 1.5 x ULN.
• •4. Albumin \> 25 g/l.
• •5. Calculated creatinine clearance (CrCl) ≥ 40 ml/min (according to cockroft and Gault formula).
• •6. Creatine phosphokinase (CPK) ≤ 2.5 x ULN.
• •10. Troponin I ≤ ULN
• •11. No prior or concurrent malignant disease in the last 5 years except for adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma.
• •12. At least three weeks since last chemotherapy (six weeks in case of nitrosoureas and mitomycin C), immunotherapy or any other pharmacological treatment and/or radiotherapy.
• •13. Recovery to grade ≤ 1 from any adverse event (AE) derived from previous treatment (excluding alopecia of any grade and non-painful peripheral neuropathy grade ≤ 2) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 4.0).
• •14. Left ventricular ejection fraction (LVEF) by echocardiogram (ECHO) or multiple gated acquisition (MUGA) within normal limits.
• •15. Women of childbearing potential must have a negative serum pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for six months after discontinuation of treatment. Acceptable methods of contraception include intrauterine device (IUD), oral contraceptive, subdermal implant and double barrier.
• •16. Patients with a french social security in compliance with the French law relating to biomedical research