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 last (first or second) platinum-containing regimen. According to the Bryant and Day design the primary endpoints will be the proportion of progression-free patients at 6 months for the efficacy, and the proportion of patients with severe toxicity for the safety at the same time-point.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
71
Arm A: bevacizumab (15 mg/kg) given as 1 hour infusion will be followed by trabectedin (1.1 mg/sqm) 3 hour iv infusion; to be repeated every 21 days until progression, unacceptable toxicity, patient or physician decision to discontinue, or death patients
Arm B: cycle 1- 6, bevacizumab given as 1 hour infusion will be followed by carboplatin AUC 4 and trabectedin 3 hour iv infusion. Cycle 7- end of treatment, bevacizumab given as 1 hour infusion will be followed by trabectedin 3 hour iv infusion. Patient enrolled in arm B will receive (cycle 1-6): trabectedin 0.8 mg/m2 ,carboplatin AUC 4 day 1 every 28 days and bevacizumab 10 mg/kg iv on day 1 and day 15. From cycle 7 to disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death patients will receive bevacizumab 15 mg/kg iv and trabectedin 1.1 mg/m2 day 1 every 21 days
Azienda Ospedaliera Spedali Civili di Brescia
Brescia, Italy
Istituto Europeo di Oncologia
Milan, Italy
AO Fatebenefratelli e Oftalmico
Milan, Italy
Azienda Ospedaliera S. Gerardo
Monza, Italy
Progression Free Survival at 6 months (PFS-6)
The PFS-6, defined as the percentage of patients who are alive and progression free at 6 months after the randomization.
Time frame: from randomization up to 6 months
Proportion of patients with severe toxicity within 6 months from randomization.
The following conditions will be considered as severe toxicity: * absolute neutrophil count (ANC) \< 0.5x109/L lasting \> 7 days and/or with fever * platelets \< 25x109/L * any other grade 3-4 (evaluated by the National Cancer Institute-Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] version 4.0) non-hematological toxicities except for reversible nausea/vomiting, diarrhea, hypersensitivity reactions, and alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation reversible to grade 1 by day 28 * any toxicity causing a delay of \>14 days in the following cycle
Time frame: from randomization up to 6 months
Progression Free Survival (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.
Time frame: from randomization up to 30 months
Overall survival at 12 months (OS-12)
Defined as the percentage of patients who are alive at 12 months after the randomization.
Time frame: one year
Clinical Benefit (CB)
clinical benefit, 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 Response Evaluation Criteria In Solid Tumors (RECIST) criteria, version 1.1 after 12 weeks from the date of randomization.
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Istituto Oncologico Veneto
Padova, Italy
Policlinico Universitario Agostino Gemelli di Roma
Roma, Italy
Mauriziano Hospital
Torino, Italy
Time frame: from randomization up to 30 months
Incidence of Adverse Events (AEs)
Incidence of AEs, according to NCI-CTCAE, version 4.0
Time frame: from randomization up to 30 months
Maximum toxicity grade
Maximum toxicity grade experienced by each patient for each specific toxicity
Time frame: from randomization up to 30 months
Percentage of patients experiencing grade 3-4 toxicity for each specific toxicity
Percentage of patients experiencing grade 3-4 toxicity for each specific toxicity during the study
Time frame: from randomization up to 30 months
Patients with at least a Serious Adverse Drug Reaction (SADR)
Patients with at least a SADR during the study
Time frame: from randomization up to 30 months
Patients with at least a Suspect Unexpected Serious Adverse Reaction (SUSAR).
Patients with at least a suspect unexpected serious adverse reaction during the study
Time frame: from randomization up to 30 months
Percentage of patients with dose and/or time modifications
Percentage of patients with dose and/or time modifications of the study drugs
Time frame: from randomization up to 30 months
Percentage of premature withdrawals
Percentage of premature withdrawals of the enrolled patients
Time frame: from randomization up to 30 months
Patients with at least a Serious Adverse Event (SAE)
Patients with at least a SAE during the study
Time frame: from randomization up to 30 months
Nature of AEs
Nature of AEs, according to NCI-CTCAE, version 4.0
Time frame: from randomization up to 30 months
Severity of AEs
Severity of AEs, according to NCI-CTCAE, version 4.0
Time frame: from randomization up to 30 months
Seriousness of AEs
Seriousness of AEs according to NCI-CTCAE, version 4.0
Time frame: from randomization up to 30 months