| Methods |
Open‐label, prospective, multicentre, randomised phase III.
Patients will be randomly assigned in a 1:1 ratio to treatment arms. |
| Participants |
242 participants
Inclusion Criteria
Female of age 18 years or older
Histologically or cytologically documented invasive epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer
Platinum resistant or sensitive patients with either:
BRCA‐mutated patients BRCAness phenotype patients: patients who have received and responded (subsequent PFI > 6 months) to at least 2 previous platinum based chemotherapy lines Platinum sensitive patients who are not able to receive or not willing to receive other platinum treatments Measurable and evaluable disease per RECIST 1.1 ECOG performance status 0 or 1 No limits in the number of previous chemotherapy lines, previous treatment with PARP inhibitors is allowed Left Ventricular Ejection Fraction (LVEF) ≥ institutional lower limit normal Life expectancy of at least 3 months
Adequate organ functions:
Haematopoietic: absolute neutrophil count ≥ 1500/mm3; platelet count ≥ 100,000/mm3; haemoglobin ≥ 9 g/dl Hepatic: AST and ALT ≤ 1.5 times upper limit of normal (ULN)* ; alkaline phosphatase ≤ 2.5 times ULN*; Bilirubin ≤ 1.5 times ULN. (NOTE: * ≤ 3 times ULN if liver metastases are present) Renal: creatinine clearance ≥ 45 ml/min or serum creatinine ≤ 1.5 x ULN Serum albumin >2.5 g/dl No other invasive malignancy within the past 3 years except non‐melanoma skin cancer or in situ cervical cancer (patients with previous cancers may be enrolled providing that no recurrences have be reported in the last 3 years) Written informed consent Adequately recovered from the acute toxicity of any prior treatment For agents in the standard arm, also refer to the local prescribing information with regard to warnings, precautions, and contraindications
Exclusion Criteria
Prior exposure to trabectedin Known hypersensitivity to any of the components of the trabectedin IV formulation or dexamethasone People with borderline ovarian cancer, i.e. people with low malignant potential tumours are excluded Less than 2 reported responses to platinum (i.e. subsequent recurrences at least 6 months after the first and the second platinum based treatment), unless BRCA mutation is documented. Less than 4 weeks from last dose of therapy with any investigational agent, or chemotherapy History of another neoplastic disease (except basal cell carcinoma or cervical carcinoma in situ adequately treated) unless in remission for 3 years or longer Known clinically relevant CNS metastases, unless treated and asymptomatic
Other serious illnesses, such as:
Congestive heart failure or angina pectoris; myocardial infarction within 1 year before enrolment; uncontrolled arterial hypertension or arrhythmias. Psychiatric disorder that prevents compliance with protocol. Active viral hepatitis; or chronic liver disease. Active infection. Any other unstable medical conditions.
|
| Interventions |
Trabectedin 1.3 mg/m2 on day 1 3‐weekly
versus
Chemotherapy of physician's choice (PLD 40 mg/m2 every 28 days or topotecan 4 mg/m2 days 1, 8, 15 every 28 days or gemcitabine 1000 mg/m2 days 1, 8, 15 every 28 days, or weekly paclitaxel 80 mg/m2 days 1, 8, 15 every 28 days or carboplatin AUC 5‐6 3‐weekly or 4‐weekly) |
| Outcomes |
Primary outcome
Overall survival (OS) (4 years)
Secondary Outcomes
Progression‐free survival (PFS) (4 years) assessed by radiological criteria; CA 125 increases alone (GCIG criteria of progression) will not be considered as progression of disease without a radiological confirmation of progression.
Duration of Response (4 years)
Adverse events (4 years)
Incidence of adverse events, according to the National Cancer Institute Common Toxicity Criteria (NCI‐CTC) version 4.0. |
| Notes |
Estimated 4‐year follow up
https://clinicaltrials.gov/ct2/show/NCT02903004
November 2022: Abstracts for conferences published but full data not yet published. Will request data for PLD‐only once further data available. |
