Multicenter, Randomized, Non-comparative, Phase II Trial on the Efficacy and Safety of the Combination of Bevacizumab and Trabectedin With or Without Carboplatin in Adult Women With Platinum Partially Sensitive Recurring Ovarian Cancer.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 71
- 试验地点
- 7
- 主要终点
- Proportion of patients with severe toxicity within 6 months from randomization.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Age≥18years
- •Eastern Cooperative Oncology Group (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)
- •One or two previous platinum-based chemotherapy lines
- •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 International Conference on Harmonization/ Good Clinical Practice (ICH/GCP).
排除标准
- •Prior treatment with trabectedin
- •Prior progression while on therapy containing bevacizumab or other vascular endothelial growth factor (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 109/l, or platelet count <100 x 109/l or haemoglobin <9 g/dl. Patients may be transfused to maintain haemoglobin values ≥9 g/dl
- •Inadequate coagulation parameters: activated partial thromboplastin time (APTT) >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/serum glutamic-oxaloacetic transaminase (SGOT) or ALT/ serum glutamic-pyruvic transaminase (SGPT) >2.5 x ULN
- •Inadequate renal function: serum creatinine >1.5 mg/dL or >132 micromol/L and urine dipstick for proteinuria > or = 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
- •hepatitis C virus (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.
研究组 & 干预措施
bevacizumab and trabectedin
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
干预措施: bevacizumab and trabectedin (Drug)
bevacizumab, trabectedin and carboplatin
Arm B: cycle 1-6, bevacizumab given as 1 hour infusion will be followed by carboplatin area under curve 4 (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
干预措施: bevacizumab, trabectedin and carboplatin (Drug)
结局指标
主要结局
Proportion of patients with severe toxicity within 6 months from randomization.
时间窗: from randomization up to 6 months
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
Progression Free Survival at 6 months (PFS-6)
时间窗: from randomization up to 6 months
The PFS-6, defined as the percentage of patients who are alive and progression free at 6 months after the randomization.
次要结局
- Percentage of patients experiencing grade 3-4 toxicity for each specific toxicity(from randomization up to 30 months)
- Patients with at least a Suspect Unexpected Serious Adverse Reaction (SUSAR).(from randomization up to 30 months)
- Overall survival at 12 months (OS-12)(one year)
- Progression Free Survival (PFS)(from randomization up to 30 months)
- Patients with at least a Serious Adverse Drug Reaction (SADR)(from randomization up to 30 months)
- Incidence of Adverse Events (AEs)(from randomization up to 30 months)
- Percentage of premature withdrawals(from randomization up to 30 months)
- Clinical Benefit (CB)(from randomization up to 30 months)
- Maximum toxicity grade(from randomization up to 30 months)
- Percentage of patients with dose and/or time modifications(from randomization up to 30 months)
- Severity of AEs(from randomization up to 30 months)
- Seriousness of AEs(from randomization up to 30 months)
- Patients with at least a Serious Adverse Event (SAE)(from randomization up to 30 months)
- Nature of AEs(from randomization up to 30 months)