A Multicenter, Randomized, Double-blind, Parallel-arm, Two-stage Study of the Efficacy and Safety of AVE0005 (VEGF Trap) Administered Intravenously Every 2 Weeks in Patients With Platinum-resistant and topotecan-and/or Liposomal Doxorubicin-resistant Advanced Ovarian Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 218
- 试验地点
- 1
- 主要终点
- Number of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Based on the Analysis by an Independent Review Committee (IRC) - Simon's Cohort
研究概览
简要总结
This study evaluated outcomes in participants with advanced ovarian epithelial adenocarcinoma receiving aflibercept.
The primary objective was to compare the objective response rate of Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) 4.0 mg/kg and 2.0 mg/kg, administered intravenously (IV) every 2 weeks with historical control in participants with advanced ovarian epithelial (including fallopian tube and primary peritoneal) adenocarcinoma resistant to platinum and topotecan and/or liposomal doxorubicin.
The secondary objectives was to further assess efficacy, safety, pharmacokinetics, potential biological and pharmacogenomic markers of study drug activity, and health-related quality of life.
This study employed an Independent Review Committee (IRC) for radiological tumor assessments. For all tumor assessment-related efficacy variables, two analyses were performed: the primary analysis was based on Independent Review Committee (IRC) reviewed data and the secondary analysis was based on Investigator evaluation. If an endpoint was evaluated by the IRC, the IRC reviewed data is reported for this study.
详细描述
The study included:
- A screening period for 21 days
- Randomization at baseline (Treatment was initiated with 5 days of randomization)
- A treatment period with 14-day study treatment cycles until a study withdrawal criterion was met
- A follow-up period up to 60 days after the end of treatment
Withdrawal criteria that led to treatment discontinuation were:
- The participant or their legally authorized representative requested to withdraw
- In the investigator's opinion, continuation of the study would be detrimental to the participant's well being, due to reasons such as disease progression, unacceptable toxicity, noncompliance, or logistical considerations.
- A specific request by the Sponsor
- Participant had intercurrent illness that prevented further administration of study treatment
- Participant had more than 2 aflibercept dose reductions
- Participant had arterial thromboembolic events, including cerebrovascular accidents, myocardial infarctions, transient ischemic attacks, new onset or worsening of pre-existing angina
- Participant had radiographic evidence of intestinal obstruction (e.g., dilated loops of bowel accompanied by air-fluid levels) or gastrointestinal perforation (e.g., presence of extraluminal gas) requiring surgical intervention
- Participant was lost to follow-up
After discontinuing treatment, participants remained on the study until the last post-treatment visit or until recovery of drug related toxicities, whichever was later.
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
- Double (Participant, Investigator)
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
- •Histologically-confirmed ovarian epithelial (including fallopian tube and primary peritoneal) adenocarcinoma.
- •Prior treatment with at least 2 treatment regimens in the advanced disease treatment setting
- •Platinum-resistant disease defined by relapse or progression of disease during or after treatment, or drug intolerance
- •Topotecan- and/or liposomal doxorubicin-resistant disease defined by relapse or progression of disease during or after treatment, or drug intolerance
- •Evidence of at least one unidimensional measurable tumor lesion by computed tomography (CT) or magnetic resonance imaging (MRI) scan according to Response Evaluation Criteria in Solid Tumors (RECIST) that has not been treated with surgery or radiation therapy
排除标准
- •Diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or for in situ carcinoma of the cervix uteri
- •Prior treatment with a vascular endothelial growth factor (VEGF) or VEGF receptor inhibitor
- •More than 3 chemotherapy regimens in the advanced disease treatment setting
- •Uncontrolled hypertension
- •The above information is not intended to contain all considerations relevant to potential participation in a clinical trial.
研究组 & 干预措施
Aflibercept 2.0 mg/kg
Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept.
干预措施: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) (Drug)
Aflibercept 4.0 mg/kg
Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept.
干预措施: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) (Drug)
结局指标
主要结局
Number of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Based on the Analysis by an Independent Review Committee (IRC) - Simon's Cohort
时间窗: From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
OR included Complete Response (CR) and Partial Response (PR). Per RECIST, CR was disappearance of all target or non-target lesions, or normalization of tumor marker levels (for non-target lesions) and PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, with baseline sum LD as reference. Tumors were assessed by an independent third-party core imaging laboratory evaluating the chest, abdomen, and pelvis by Computerized Tomography (CT) scans or Magnetic Resonance Imaging (MRI) scans; and responses were confirmed by repeat tumor imaging 4-6 weeks later.
Number of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Based on the Analysis by the IRC - Efficacy Evaluable Population
时间窗: From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
OR included Complete Response (CR) and Partial Response (PR). Per RECIST, CR was disappearance of all target or non-target lesions, or normalization of tumor marker levels (for non-target lesions) and PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, with baseline sum LD as reference. Tumors were assessed by an independent third-party core imaging laboratory evaluating the chest, abdomen, and pelvis by Computerized Tomography (CT) scans or Magnetic Resonance Imaging (MRI) scans; and responses were confirmed by repeat tumor imaging 4-6 weeks later.
次要结局
- Number of Participants With a Clinical Benefit Response (CBR) as Per RECIST Based on the Analysis by the IRC(From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months))
- Duration of Response (DR) Based on the Analysis by an Independent Review Committee (IRC)(From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months))
- Time to Tumor Marker (CA-125) Progression (TTMP)(From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months))
- Progression-free Survival (PFS) Time Based on Analysis by the IRC(From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months))
- Overall Survival (OS) Time(From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months))
- Tumor Marker Response Rate (TMRR) Based on the Gynecologic Cancer Intergroup (GCIG) Definition(From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months))
- Time to Tumor Progression (TTP) as Per RECIST Based on the Analysis by the IRC(From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months))
- Overall Safety - Number of Participants With Adverse Events (AE)(up to 30+/-5 days after treatment discontinuation, or up to recovery or stabilization of a followed-up adverse event)
- Participant's Assessment of Health Related Quality of Life (HRQL) Using a by Using the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) Questionnaire(On Day 1 of Cycle 1 (baseline) , and after Day 14 of Cycle 2)
- Number of Participants With Disease Progression Events for Progression-free Survival (PFS) Analysis by the IRC.(From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months))