Reprab Study: PLD + Trabectedin Rechallenge

Inclusion criteria:

• Female aged ≥ 18 years.
• Histologically or cytologically documented invasive epithelial ovarian cancer, primaryperitoneal carcinoma, or fallopian tube cancer
• Platinum partially sensitive patients or fully platinum sensitive patients not able toreceive or not willing to receive other platinum treatments, who have previouslyreceived pegylated liposomal doxorubicin (carboplatin- pegylated liposomal doxorubicinor pegylated liposomal doxorubicin alone).
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0- 1.
• Subject has radiographically-documented measurable disease, as per RECIST 1.1 at studyentry (CA-125 rise not supported by radiological evidence of disease is not acceptedas criteria for defining progression).
• Be able to receive IV dexamethasone or an equivalent IV corticosteroid.
• Have all of the following: hemoglobin ≥9 g/dL (without transfusion in the prior 7 days). Subjects may be enrolled intothe study while receiving recombinant erythropoietin provide they have received recombinanterythropoietin for at least 4 weeks. before the first dose of study drug. albumin >25 g/L absolute neutrophil count (ANC) >1,500/μL platelet count >100,000/μL (without transfusion in the prior 7 days) either a serum creatinine <=1.5 mg/dL or acalculated glomerular filtration rate >60 mL/min/1.73 m2 (Cockcroft-Gault) CPK <2.5 x upperlimit of normal (ULN) Have total bilirubin <xULN. If total bilirubin is > 1,5xULN, measuredirect and indirect bilirubin to evaluate for Gilbert's syndrome (if direct bilirubin iswithin normal range, subject may be eligible). Have alkaline phosphatase (ALP) 2.5xULN; if the ALP is >2.5xULN, then an ALP liver fractionor 5' nucleotidase must be <ULN (as reported in absolute units of measure). Have AST and ALT 2.5xULN. Have LVEF by MUGA scan or 2D-ECHO within normal limits for theinstitution.
• Patients must be in postmenopausal (at least 12 months consecutive amenorrhea, in theappropriate age group and without other known or suspected cause), or have beensterilized surgically
• Adequate recovery from acute toxicity of any prior treatment

Exclusion criteria:

• Non-epithelial ovarian or mixed epithelial/non epithelial tumors (e.g., Mulleriantumors)
• Patients who did not respond to last platinum-based therapy or in whom last relapseoccurred < 6 months from the last dose of platinum
• Bowel obstruction, sub-occlusive disease or the presence of symptomatic brainmetastases
• Known hypersensitivity to any of the components of pegylated liposomal doxorubicin orTRABECTEDIN i.v. formulation
• Previous treatment with Trabectedin
• Known hypersensitivity to dexamethasone
• Less than 4 weeks from last dose of therapy with any investigational agent, orchemotherapy.
• History of another neoplastic disease (except basal cell carcinoma or cervicalcarcinoma in situ adequately treated) unless in remission for 3 years or longer
• Myocardial failure within six months before enrolment, New York
• Association (NYHA) Class II or worse heart failure, uncontrolled angina, severeuncontrolled ventricular arythmias, clinically significant pericardial disease, orelectrocardiographic evidence of acute ischemic or active conduction systemabnormalities
• Known significant chronic liver disease, such as cirrhosis or active hepatitis (potential subjects who test positive for hepatitis B surface antigen or hepatitis Cantibodies are allowed provided they do not have active disease requiring antiviraltherapy). Also known history of liver carcinoma and cholangitis with abnormal liverfunctionality
• Concurrent severe medical problems or any unstable medical condition unrelated tomalignancy, which would significantly limit full compliance with the study or exposethe patient to extreme risk or decreased life expectancy
• Known clinically relevant CNS metastases
• Psychiatric disorder that prevents compliance with protocol
• Patients with concurrent serious or uncontrolled infection
• Patients in need of yellow fever vaccine while on study chemotherapy
• Active infection
• Breastfeeding women
• Pregnant women
• Any other unstable medical condition