Trial Comparing Trabectedin to the Best Supportive Care in Patients With Sarcoma

Inclusion criteria

• Informed consent understood, agreed and signed
• Tolerance of the central venous line that will be used for Trabectedin infusions.
• Pathologically confirmed diagnosis of STS at the investigator centre level (and confirmed by Rrepps Network), except the following cases :

• Low grade fibromyxoid sarcoma (LGFMS),
• Giant Cells Fibroblastoma,
• Dermatofibrosarcoma protuberances (DFSP),
• Angiomatoid fibrous histiocytoma,
• Alveolar Rhabdomyosarcoma and Embryonal Rhabdomyosarcoma,
• Mesenchymal and Non-Mesenchymal Chondrosarcoma,
• Extraskeletal Ewing Sarcoma / Primitive Neuroectodermal Tumour (PNET),
• Desmoplastic small round-cell tumour (DSRCT ),
• Gastro-Intestinal Stromal Tumour (GIST),
• Endometrial Stroma Sarcoma,
• Osteosarcoma.
• Histological samples available for centralised histopathological diagnosis and the appropriate genetic diagnosis.
• Patient who already received no more than 3 previous therapy lines. Therefore, trabectedin might be administered as a 2nd, 3rd or 4th therapy line in case of metastatic STS.
• Measurable disease as per RECIST (Response Evaluation Criteria In Solid Tumors), and confirmed based on objective data within 14 days prior to study inclusion.
• Disease progression according to RECIST 1.1 confirmed by imaging evaluation within 14 days prior to study inclusion comparatively to imaging within the previous 6 months.
• ECOG (Eastern Cooperative Oncology Group) Performance score: 0 or 1.
• Normal cardiac function as assessed by cardiac ultrasound examination or by MUltiple Gated Acquisition scan (MUGA scan).
• Biological laboratory parameters meeting the following criteria within 14 days prior to study inclusion:

• neutrophil leucocytes ≥ 1500 /μL,
• haemoglobin ≥ 9,0 g/100 mL,
• platelet count 100 x 103 /μL
• AST (aspartate aminotransferase) ≤ 2.5 times the investigator local laboratory upper normal limit (UNL),
• ALT (alanine aminotransferase) ≤ 2.5 times the investigator local laboratory UNL,
• Alkaline phosphatases ≤ 2.5 UNL,
• bilirubin ≤ UNL ,
• CPK ≤ 2.5 times the investigator laboratory UNL,
• albumin ≥ 25 g/L
• creatinine clearance measured or calculated (Cockcroft-Gault formula) ≥ 30 mL/min.
• Patient having reached the majority age at the time they sign the informed consent.
• Life expectancy of at least 3 months at study entry.
• Patient covered by the health insurance system.
• All women of childbearing potential must have a negative serum pregnancy test within 14 days prior to study inclusion.

Exclusion criteria

• Hypersensitivity, history of allergic reaction to trabectedin
• History of allergic reaction or known hypersensitivity to dexamethasone or to anti-emetic agents belonging to the triptan family (i.e., 5-HT3 receptor antagonists).
• History of allergic reaction or known hypersensitivity to contrast agents (except if the patient's tumour can be evaluated using MRI without contrast agents).
• Severe concomitant disease (such as pulmonary fibrosis, interstitial pneumonitis, renal insufficiency, liver failure, cerebrovascular disease, malignant disease requiring blood transfusions, or uncontrolled diabetes).
• Clinically significant abnormalities of the electrocardiogram test, or one of the following clinically significant cardiac diseases :

• Congestive cardiac insufficiency,
• Active coronary disease,
• Arrhythmia poorly controlled by medicinal products only,
• Myocardial infarction within one year prior to study entry.
• Surgery under general anaesthesia within 28 days prior to study entry, exploratory surgery (thoracotomy or laparotomy) within 28 days prior to study entry,.
• Treatment with one of the following anticancer agents prior to study entry :

• hormonotherapy within 14 days prior to study entry,
• other anticancer treatment (such as chemotherapy, targeted therapy, or biological advanced therapy) within 21 days prior to study entry.
• Radiotherapy within 21 days prior to study entry.
• History of graft transplantation or stem cell transplantation.
• Adverse reaction to a previous treatment, other than alopecia, long-lasting, and of grade ≥ 2 severity according to CTCAE (v. 4.0) criteria.
• Intercurrent infection requiring a systemic antimicrobial treatment (e.g., associated with fever ≥ 38° C),
• Patients HIV positive and/or viral anti-therapy and/or hepatitis B and/or C. Systematic serology to check the status is not necessary.
• Brain metastasis, either symptomatic or requiring a treatment.
• History of another cancer within 5 years prior to study entry (except intra-epithelial neoplasm or basocellular cancer, if they are cured, e.g., thanks to surgical resection or radiotherapy).
• Psychiatric disorders disturbing the informed consent process.
• Pregnant or breast-feeding woman; man or woman not complying to contraceptive measures during the following time periods:

• For the men, during the full study up to 5 months after the last study treatment administration;
• For the women, femmes, during the full study up to 3 months after the last study treatment administration.
• Other investigational treatment within 28 days prior to study entry.
• Prior treatment with trabectedin.
• Any clinical conditions not compatible with an adequate study conduct, according to investigator's judgement.
• Patient under administrative or legal supervision, patient hospitalised without his/her consent or for other purposes than research, patient under guardianship or curators, or unable to express his/her consent.