adult women with platinum partially sensitive recurring ovarian cancer. MedDRA version: 14.1 Level: LLT Classification code 10033271 Term: Ovarian neoplasia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: YONDELIS*EV 1FL POLV 1MG
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: trabectedin
CAS Number: 114899-77-3
Concentration unit: µg microgram(s)
Concentration t
Sponsors
IST. DI RICERCHE FARMACOLOG. M. NEGRI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age=18years ECOG-performance status 0-2 Cytological/histological diagnosis of epithelial ovarian cancer Progression free interval between 6-12 months (calculated from the first day of the last cycle of the previous last platinum-based chemotherapy until the date of progression confirmation through radiologic imaging). Only one previous platinum-based chemotherapy line Measurable disease according to RECIST version 1.1 Life expectancy = 12 weeks Patients must be able to receive dexamethasone or its equivalent, as a premedication for trabectedin Written informed consents given before the enrolment according to ICH/GCP. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 14
Exclusion criteria
Exclusion criteria: Prior treatment with trabectedin Prior progression while on therapy containing bevacizumab or other VEGF pathway–target therapy Pre-existing grade > 1 sensitive/motor neurologic disorder Current or recent (within 30 days of first study dosing) treatment with another investigational drug Surgery (including open biopsy) within 4 weeks prior to the first planned dose of bevacizumab Current or recent (within 10 days prior to the first study drug dose) use of full-dose oral or parenteral anticoagulant or thrombolytic agent for therapeutic purposes (except for line patency, in which case international normalized ratio [INR] must be maintained below 1.5). Post operative prophylaxis with low molecular weight heparin sc is allowed Inadequate bone marrow function: absolute neutrophil count (ANC): 1.5 x upper limit of normal (ULN) or INR >1.5 Inadequate liver function, defined as: serum (total) bilirubin > ULN for the institution AST/SGOT or ALT/SGPT >2.5 x ULN Inadequate renal function: serum creatinine >1.5 mg/dL or >132 ?mol/L and urine dipstick for proteinuria ?2+ and >1g of protein in their 24-hour urine collection History or evidence of brain metastases or spinal cord compression Pregnant, breastfeeding women and women of child bearing potential, who do not agree to use a medically acceptable method of contraception through the treatment period and for 6 months after discontinuation of treatment History or evidence of thrombotic or hemorrhagic disorders; including cerebrovascular accident, stroke or transient ischemic attack or sub-arachnoid haemorrhage within 6 months prior to the first study treatment Uncontrolled hypertension (sustained systolic >150 mmHg and/or diastolic >100 mmHg despite antihypertensive therapy) or clinically significant (i.e. active) cardiovascular disease, including: myocardial infarction or unstable angina within 6 months prior to the first study treatment, New York Heart Association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication History of bowel obstruction, including subocclusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess. Evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction Non-healing wound, ulcer or bone fracture HCV positivity Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This study is aimed at assessing the efficacy and the safety of the combination of bevacizumab and trabectedin with or without carboplatin in adult women with epithelial ovarian cancer at first recurrence occurred 6-12 months after the end of the first platinum-containing regimen. According to the Bryant and Day design the primary endpoints will be the proportion of progression-free patients at 6 months (PFS-6) for the efficacy, and the proportion of patients with severe toxicity for the safety at the same time-point. Disease progression will be determined using the RECIST criteria, version 1.1.;Secondary Objective: To evaluate: PFS, defined for each patient as the time from the date of randomization to the date of first progression, second primary malignancy or death for any cause, whichever comes first. Subjects not progressed or died at the time of the analysis will be censored at the last disease assessment date. 12 month overall survival (OS-12), defined as the percentage of patients who are alive at 12 months after the randomization. Clinical benefit, defined as the percentage of patients who are judged by the Investigators to have a complete response, or partial response or stable disease according to the RECIST criteria, version 1.1 after 4 cycles of treatment the treatment compliance. the safety profile, evaluated by the NCI-CTCAE scale, version 4.0 and by the occurrence of serious adverse reactions.;Primary end point(s): the proportion of progression-free patients at 6 months (PFS-6) for the efficacy, and the proportion of patients with severe toxicity for the safety at the same time-point. Disease progression will be determined using the RECIST criteria, version 1.1. The following conditions will be considered as severe toxicity: 1. absolute neutrophil count (ANC) 7 days and/or with fever 2. platelets 14 days in the following cycle;Timepoint(s) of evaluation of this end point: PFS-6 and safety will be evalueted at 6 mon | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy endpoints: The PFS, defined for each patient as the time from the date of randomization to the date of first progression, second primary malignancy or death for any cause, whichever comes first. Subjects not progressed or died at the time of the analysis will be censored at the last disease assessment date. Disease progression will be determined using the RECIST criteria, version 1.1. The 12 month overall survival (OS-12), defined as the percentage of patients who are alive at 12 months after the randomization. the clinical benefit (CB), defined as the percentage of patients who are judged by the Investigators to have a complete response (CR), or partial response (PR) or stable disease (SD) according to the RECIST criteria, version 1.1 after 12 weeks from the date of randomization. Compliance endpoints Percentage of patients with dose and/or time modifications Percentage of premature withdrawals. Safety endpoints Incidence, nature, severity and seriousness of AEs, according to NCI-CTCAE, version 4.0 Maximum toxicity grade experienced by each patient for each specific toxicity Percentage of patients experiencing grade 3-4 toxicity for each specific toxicity Patients with at least a SAE Patients with at least a serious adverse drug reaction (SADR) Patients with at least a suspect unexpected serious adverse reaction (SUSAR).;Timepoint(s) of evaluation of this end point: 12 months | — |
Countries
Italy
Contacts
Public Contactunità coordinamento studi clinici
Istituto di Ricerche Farmacologiche Mario Negri
Outcome results
None listed