NCT02383251已完成2 期
A Randomized Phase II Study of Pazopanib and Weekly Paclitaxel in Patients With Platinum Resistant/Refractory Ovarian Cancer Who Relapse During Bevacizumab Maintenance
ARCAGY/ GINECO GROUP36 个研究点 分布在 1 个国家目标入组 118 人开始时间: 2015年6月15日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 118
- 试验地点
- 36
- 主要终点
- Progression free survival (PFS)
研究概览
简要总结
Study of Pazopanib and weekly Paclitaxel in patients with platinum resistant/refractory ovarian cancer who relapse during bevacizumab maintenance.
详细描述
Standard of treatments:
- In Europe, advanced ovarian cancer patients are treated in first line with optimal debulking surgery followed by carboplatin/paclitaxel regimen plus bevacizumab during chemotherapy and as maintenance for a total à 15 months. The addition of bevacizumab is a standard for the patients with residual disease.
- The addition of bevacizumab to carboplatin/gemcitabine chemotherapy was also recently approved for patients with platinum sensible relapse [Aghajanian, 2012]. The bevacizumab is maintained until progression.
Rationale to use anti-angiogenic agents in early relapse:
- The recent AURELIA trial comparing paclitaxel, topotecan or liposomal doxorubicin alone versus combined to bevacizumab after early failure of the first-line with carboplatin/paclitaxel revealed that targeting angiogenesis was beneficial in recurrent platinum-resistant ovarian cancer [Pujade-Lauraine, 2012 and 2013], with higher progression-free survival (PFS). Thus, the strategy of inhibiting angiogenesis in recurrent resistant-platinum ovarian cancer is very promising.
- The recent changes of the standard of treatment of first line and platinum-sensible relapse of patients with ovarian cancer highlights the question of inhibiting angiogenesis for relapse during/after bevacizumab maintenance. In this last situation, the strategy of continuation of antiangiogenesis therapy, just in changing chemotherapy despite recurrence, showed benefit in other types of cancer (colon, lung). In ovarian cancer, no study has been performed to answer to the question. In Aurelia trial, However, patients did not previously receive bevacizumab.
The choice of the best antiangiogenic agent in alternative to bevacizumab needs to be assessed. Small molecular inhibitor of tyrosine-protein-kinases (TK) could be used with efficacy after a first-line of antiangiogenesis treatment as it was demonstrated in renal cancer [Escudier, 2011].
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 95 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Performance status ECOG < 2
- •Histological documented ovarian, tubal or peritoneum carcinoma (stage IC to IV)
- •Patient treated at least with one line of platinum-based chemotherapy who have relapsed within 6 months after trhe last administration of platinum-based chemotherapy and taking bevacizumab for maintenance NB: Penultimate line of chemotherapy could contain chemotherapy without platinum and the last line should contain platinum-based chemotherapy (followed by bevacizumab for maintenance)
- •Patients must have disease that is measurable and/or evaluable according to RECIST criteria and requires chemotherapy treatment
- •Patients with liver metastasis can be included
- •Subjects must provide written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow up.
- •Life expectancy of more than 3 months
- •Able to swallow and retain oral medication
- •Adequate organ system function like:
- •Total bilirubin ≤ 1.5 X ULN Alanine amino transferase (ALT) and Aspartate aminotransferase (AST)c ≤ 2.5 X ULN
- •Subjects may not have had a transfusion within 7 days of screening assessment.
- •Subjects receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation.
- •Concomitant elevations in bilirubin and AST/ALT above 1.0 x ULN (upper limit of normal) are not permitted.
- •If UPC <1, then a 24-hour urine protein must be assessed. Subjects must have a 24-hour urine protein value <1 g to be eligible. Use of urine dipstick for renal function assessment is not acceptable.
- •Women of childbearing potential must agree to use effective contraception
- •Negative serum pregnancy test (if applicable)
- •Affiliated to or a beneficiary of a social security category
排除标准
- •Prior malignancy over the past 5 years with the exception of in situ carcinomas of the cervix or basal and squamous cell carcinoma or nonmelanoma skin cancer properly treated, or all solid tumor, considered as in completed remission without relapse for at least 5 years
- •Central nervous system (CNS) metastases at baseline, with the exception of those subjects who have previously-treated CNS metastases (surgery ± radiotherapy) and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants of P3A4 cytochrom
- •Previous treatment with monotherapy weekly paclitaxel
- •Previous treatment with bevacizumab within three weeks before start of studt treatment
- •Patients with severe hypersensitivity to a product containing castor oil polyoxyl 35 or paclitaxel solvent: the Chremophor
- •Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
- •Active peptic ulcer disease
- •Known intraluminal metastatic lesion/s with risk of bleeding
- •Inflammatory bowel disease (e.g. ulcerative colitis, Chrohn's disease), or other gastrointestinal conditions with increased risk of perforation
- •History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
- •Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:
- •Malabsorption syndrome
- •Major resection of the stomach or small bowel.
- •Corrected QT interval (QTc) > 450 msecs or > 480 msecs for patient with block branch
- •History of any one or more of the following cardiovascular conditions within the past 6 months:
- •Cardiac angioplasty or stenting
- •Myocardial infarction
- •Unstable angina
- •Coronary artery bypass graft surgery
- •Symptomatic peripheral vascular disease
- •Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
- •Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg].
- •History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible
- •Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major surgery).
- •to 14: All risk of bleeding
- •15 Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures. 16 Unable or unwilling to discontinue use of prohibited medications 17 Treatment with any of the following anti-cancer therapies:
- •radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib (out of bevacizumab) OR
- •chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib (out of bevacizumab) 18 Administration of any non-oncologic investigational drug within 30 days or 5 half lives whichever is longer prior to receiving the first dose of study treatment 19 Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia. 20 Patient deprived of liberty or state-controlled 21 Inability to participate to medical follow up for geographic
研究组 & 干预措施
Pazopanib/Paclitaxel association
Experimental
Arm 1 :
Pazopanib alone during 1 week at 600 mg (1x400mg and 1x200mg), per day, taken orally without food at least one hour before or two hours after a meal.
Then:
- Pazopanib 600 mg (1x400mg and 1x200mg), per day, taken orally without food at least one hour before or two hours after a meal.
- Paclitaxel 65 mg/m2 i.v. on days 1, 8, 15 every 28 days until progression of disease or toxicity
干预措施: Pazopanib (Drug)
Pazopanib/Paclitaxel association
Experimental
Arm 1 :
Pazopanib alone during 1 week at 600 mg (1x400mg and 1x200mg), per day, taken orally without food at least one hour before or two hours after a meal.
Then:
- Pazopanib 600 mg (1x400mg and 1x200mg), per day, taken orally without food at least one hour before or two hours after a meal.
- Paclitaxel 65 mg/m2 i.v. on days 1, 8, 15 every 28 days until progression of disease or toxicity
干预措施: Paclitaxel (Drug)
Paclitaxel alone
Active Comparator
Arm 2 :
- Paclitaxel 80mg/m2 i.v. on days 1, 8, 15
- every 28 days until progression of disease or toxicity
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Progression free survival (PFS)
时间窗: 4 months
Proportion of progression or death 4 months after initiation of treatment
次要结局
- Toxicity according to NCI CTCAE v4.3 criteria(Up to 2 years)
- health-related quality of life(Up to 2 years)
- Overall survival(Up to 2 years)
- Disease control rate (DCR)(Up to 2 years)
研究者
研究点 (36)
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