Gynaecological cancer, ovarian cancer Cancer Malignant neoplasm of ovary
Conditions
Interventions
Yondelis & PLD versus Carboplatin & PLD
Patients are either given trabectedin (Yondelis®) and pegylated liposomal doxorubicin (PLD) or carboplatin and PLD
Sponsors
Mario Negri Gynecological Oncology Group - MaNGO (Italy)
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: 1. Female, aged = 18 years 2. Histologically and/or cytologically proven epithelial ovarian, epithelial fallopian tube cancer or primary peritoneal cancer 3. Progression-free interval between six and twelve (6-12) months (calculated from the first day of the last cycle of the last platinum-based chemotherapy until the date of progression confirmation through radiologic imagery). Patients may have received up to two platinum-based chemotherapy lines, of which at least one must have contained a taxane 4. Measurable or evaluable disease confirmed by radiological imaging, such as magnetic resonance imaging (MRI), computed tomography (CT) scan, or PET/CT scan at study entry. CA-125 rise not supported by radiological evidence of disease is not accepted as criteria for defining progression) or histological proven recurrent ovarian cancer even in the absence of postoperatively measurable or evaluable lesions 5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 2 6. Estimated life expectancy = 12 weeks 7. Patients must be accessible for treatment and follow-up 8. Adequate organ function within 14 days prior to first cycle as evidenced by: 8.1. Peripheral blood counts and serum chemistry values: 8.1.1. Hemoglobin ³ 9 g/dl 8.1.2. Absolute neutrophil count (ANC) ³ 1,500/ml 8.1.3. Platelet count ³ 100,000/ml 8.1.4. Estimated glomerular filtration rate > 60 ml/min according to the Cockroft-Gault formula 8.1.5. Creatine phosphokinase (CPK) = 2.5 x ULN 8.2. Hepatic function variables: 8.2.1. Total bilirubinULN 8.2.2. Total alkaline phosphatase 2.5 ULN (consider hepatic isoenzymes 5-nucleotidase if the elevation could be osseous in origin) 8.2.3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be £ 2.5 x ULN 9. Patients must be able to receive dexamethasone or its equivalent, which is required if randomly assigned to treatment with trabectedin plus PLD 10. Informed consent of the patient
Exclusion criteria
Exclusion criteria: 1. Non-epithelial ovarian or mixed epithelial/non epithelial tumors (e.g., Mullerian tumors) 2. Patients who did not respond to last platinum-based therapy or in whom last relapse occurred 12 months from the last dose of platinum 3. Bowel obstruction, sub-occlusive disease or the presence of symptomatic brain metastases 4. Pre-existing grade > 1 motor or sensory neuropathy according to the National Cancer Institute Common Toxicity Criteria Adverse Event (NCI-CTCAE) version 4.0 5. Myocardial infarct within six months before enrolment, New YorkHeart Association (NYHA) Class II or worse heart failure, uncontrolled angina, severe uncontrolled ventricular arrythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities 6. History of liver disease 7. Concurrent severe medical problems or any unstable medical condition unrelated to malignancy, which would significantly limit full compliance with the study or expose the patient to extreme risk or decreased life expectancy 8. Breastfeeding women and women of child bearing potential must use effective contraception during treatment and 3 months thereafter, which may include prescription contraceptives (oral, injection, or patch), intrauterine device, double-barrier method or male partner sterilization (not applicable to patients that are surgically sterile) 9. Prior exposure to trabectedin 10. Prior resistance to anthracyclines or PLD defined as a progression during anthracycline-based chemotherapy or a recurrence within 6 months from its ending 11. Prior severe PLD related toxicity 12. Prior exposure to cumulative doses of doxorubicin >400mg/m2 or epirubicin >720mg/m2 13. Treatment with any investigational product within 30 days prior to inclusion in the study 14. Patients with known hypersensitivity to Trabectedin and any of its excipients or yellow fever vaccine 15. Patients with concurrent serious or uncontrolled infection 16. Patients in need of yellow fever vaccine while on study chemotherapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Demonstrate that the combination of trabectedin (Yondelis®) and pegylated liposomal doxorubicin | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. CA-125 response 2. To evaluate serological response of CA-125 in each arm 3. Quality of life 4. To compare the quality of life (QoL) in each arm using the European Organization for Research 5. Safety Profile 6. To compare safety profile, progression free survival (PFS), objective response rate (ORR) Sub study (Italy only): 1. To perform pharmacokinetic (PK) analyses in both plasma 2. Time to subsequent chemotherapy 3. To evaluate the time from randomization to subsequent chemotherapy and the overall survival counted | — |
Countries
Denmark, England, Finland, Germany, Italy, Spain, United Kingdom
Outcome results
None listed