Randomized Controlled Study Comparing AEZS-108 With Doxorubicin as Second Line Therapy for Locally Advanced, Recurrent or Metastatic Endometrial Cancer.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 511
- 试验地点
- 123
- 主要终点
- Compare the Overall Survival (OS) of Patients Treated With AEZS-108 to the OS of Patients Treated With Doxorubicin.
研究概览
简要总结
Open-label, randomized, active-controlled, two-arm Phase III study to compare the efficacy and safety of AEZS-108 and doxorubicin.
详细描述
The study will include about 500 patients with endometrial cancer resistant to platinum/taxane-based chemotherapy.
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
- •Women ≥ 18 years of age
- •Histologically confirmed endometrial cancer
- •Advanced (FIGO stage III or IV), recurrent or metastatic disease.
- •Measurable or non-measurable disease that has progressed since last treatment.
- •Patients with advanced, recurrent or metastatic endometrial cancer who have received one chemotherapeutic regimen with platinum and taxane (either as adjuvant or as first line treatment) and who have progressed.
- •Availability of fresh or archival FFPE (formalin-fixed and paraffin-embedded) tumor specimens for analysis of LHRH (luteinizing hormone releasing hormone) receptor expression.
排除标准
- •ECOG (Eastern Cooperative Oncology Group) performance status >
- •Inadequate hematologic, hepatic or renal function
- •Red blood cell transfusion within 2 weeks prior to anticipated start of study treatment.
- •History of myocardial infarction, acute inflammatory heart disease, unstable angina, or uncontrolled arrhythmia within the past 6 months.
- •Impaired cardiac function defined as left ventricular ejection fraction (LVEF) < 50 % (or below the study site's lower limit of normal) as measured by MUGA (multigated radionuclide angiography) or ECHO (echocardiography).
- •Concomitant use of prohibited therapy (specified in protocol)
- •Chemo-, immune-, or hormone-therapy within 5 elimination half life times or 4 weeks prior to randomization, whichever is the shorter. Radiotherapy (including pre- or post-operative brachytherapy) within 4 weeks prior to randomization.
- •Previous anthracycline-based chemotherapy (daunorubicin, doxorubicin, epirubicin, idarubicin, mitoxantrone and valrubicin), in any formulation.
- •Anticipated ongoing concomitant anticancer therapy during the study.
- •History of serious co-morbidity or uncontrolled illness that would preclude study therapy, such as active tuberculosis or any other active infection.
- •Brain metastasis, leptomeningeal disease.
- •Pregnant or lactating female or female of child-bearing potential not employing adequate contraception.
- •Subjects with known hypersensitivity to peptide drugs, including LHRH agonists.
- •Receipt of 2 or more prior cytotoxic chemotherapy regimens for advanced, recurrent, or metastatic endometrial cancer.
- •Prior treatment with AEZS-
- •Use of LHRH agonist or antagonist treatment within 6 months prior to randomization.
- •Malignancy within last 5 years except non-melanoma skin cancer.
- •Any concomitant disease or condition which would interfere with the subjects' proper completion of the protocol assignment.
- •Concomitant or recent treatment with other investigational drug (within 4 weeks or 5 elimination half life times prior to anticipated start of study treatment).
- •Lack of ability or willingness to give informed consent.
- •Anticipated non-availability for study visits/procedures.
研究组 & 干预措施
AEZS-108 / zoptarelin doxorubicin
267 mg/m^2 by 2-hour intravenous infusion, on Day 1 of 21-day (3-week) cycles up to 9 cycles
干预措施: AEZS-108 / zoptarelin doxorubicin (Drug)
doxorubicin/ standard chemotherapy
60 mg/m^2 by intravenous bolus injection or 1-hour intravenous infusion, on Day 1 of 21-day (3-week) cycles
干预措施: doxorubicin (Drug)
结局指标
主要结局
Compare the Overall Survival (OS) of Patients Treated With AEZS-108 to the OS of Patients Treated With Doxorubicin.
时间窗: From randomization to death from any cause. During ongoing treatment: response evaluation every 3 cycles. For patients gone of treatment: re-assessment every 12 weeks.
Overall survival was defined as the elapsed time from randomization to death from any cause. For surviving patients, follow-up was to be censored at the date of last contact. The final analysis, which was event-based, was conducted after approximately 384 randomized patients had died. A log-rank test with an overall two sided Type I Error rate of 0.05 after taking the interim analyses into account was used to compare OS between the two treatment arms via a SAS (Statistical Analysis System) LIFETEST procedure. Kaplan Meier estimates were used to calculate median OS and the 95% confidence interval (CI) of the median OS. The proportion of patients alive at 6 and 12 months (from randomization date) and the 95% CIs for these estimated proportions were calculated.
次要结局
- Compare Efficacy Based on Objective Response Rate (ORR).(3 years)
- Compare Efficacy Based on Progression-free Survival (PFS).(During ongoing treatment: response evaluation every 3 cycles. For patients gone of treatment: re-assessment every 12 weeks.)
- Compare Efficacy Based on Clinical Benefit Rate (CBR).(3 years)