A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Assess the Efficacy and Safety of Farletuzumab (MORAb 003) in Combination With Carboplatin Plus Paclitaxel or Carboplatin Plus Pegylated Liposomal Doxorubicin (PLD) in Subjects With Low CA125 Platinum-Sensitive Ovarian Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Eisai Inc.
- 入组人数
- 332
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
MORAb-003-011 is a global, multicenter, double-blind, randomized placebo-controlled study to assess the safety and efficacy of farletuzumab in combination with standard chemotherapy in subjects with low cancer antigen 125 (CA125) platinum-sensitive ovarian cancer in first relapse.
详细描述
Participants will be enrolled into 1 of 2 chemotherapy treatment arms at the investigator's discretion: carboplatin plus paclitaxel or carboplatin plus Pegylated Liposomal Doxorubicin (PLD), and then randomized in a 2:1 ratio to receive weekly farletuzumab 5 mg/kg or placebo (ie, Test Article). All participants will receive a loading dose for the first 2 weeks of 10 mg/kg Test Article (farletuzumab or placebo). Participants will be stratified at randomization by individual chemotherapy treatment regimen (targeted 1:1 ratio) and platinum-free interval following first-line therapy (6 to 12 months vs greater than 12 to 36 months).
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
- •Female subjects who are at least 18 years of age at the time of informed consent
- •CA125 less than or equal to 3 x upper limit of normal (ULN) [105 units per millilitre (U/mL)] confirmed within 2 weeks of randomization using a centralized laboratory assay
- •A histologically confirmed diagnosis of high-grade serous epithelial ovarian cancer including primary peritoneal and fallopian tube malignancies; all other histologies, including mixed histology, are excluded
- •Have been treated with debulking surgery and a first-line platinum-based chemotherapy regimen
- •Maintenance therapy during the first platinum-free interval is allowed; however, the last dose must have been at least 21 days prior to Randomization.
- •Must be in a first relapse and have evaluable disease by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan, according to RECIST 1.1 (subjects with measurable disease per RECIST 1.1 or radiographically visible and evaluable disease). Subjects with only ascites or pleural effusion are excluded.
- •Must have relapsed radiographically between 6 months and 36 months of completion of first-line platinum chemotherapy
- •Must be a candidate for treatment with either carboplatin plus paclitaxel or carboplatin plus PLD with no medical contraindications present as outlined in the product labels for the selected regimen to be used in this study
- •Have a life expectancy of at least 6 months, as estimated by the investigator
- •Other significant medical conditions must be well-controlled and stable in the opinion of the investigator for at least 30 days prior to Randomization
- •Have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- •Subjects being enrolled to receive paclitaxel plus carboplatin treatment must have neuropathic function (sensory and motor less than or equal to Grade 2 according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v4.03 (2010)
- •Laboratory results within the 2 weeks prior to Randomization must be as follows:
- •Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9/L
- •Platelet count greater than or equal to 100 x 10^9/L
- •Hemoglobin greater than or equal to 9 g/dL
- •Creatinine less than 1.5 x ULN (CTCAE Grade 1)
- •Bilirubin less than 1.5 x ULN (CTCAE Grade 1)
- •Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) less than 3 x ULN
- •Alkaline Phosphatase less than 2.5 x ULN (CTCAE Grade 1)
- •Baseline albumin greater than or equal to Lower Limit of Normal
- •Subjects of childbearing potential must be surgically sterile or consent to use a medically acceptable method of contraception throughout the study period. All females will be considered to be of childbearing potential unless they are postmenopausal (eg, amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing). If a patient of childbearing potential is neither surgically sterile nor postmenopausal, a highly-effective contraceptive method (ie, a method that can achieve a failure rate of less than 1 percent (%) per year when used consistently and correctly) must start either before or at Screening and continue throughout the entire study period and for 6 months after the last dose of Test Article is administered. Pregnant and/or lactating females are excluded
排除标准
- •Known central nervous system (CNS) tumor involvement
- •Evidence of other active invasive malignancy requiring treatment other than surgery in the past 3 years
- •Clinically significant heart disease (eg, congestive heart failure of New York Heart Association Class 3 or 4 angina, not well controlled by medication, or myocardial infarction within 6 months)
- •Electrocardiogram (ECG) demonstrating clinically significant arrhythmias that are not adequately medically managed (Note: subjects with chronic atrial arrhythmia, ie, atrial fibrillation or paroxysmal supraventricular tachycardia [SVT], are eligible)
- •Active serious systemic disease, including active bacterial or fungal infection
- •Active viral hepatitis or active human immunodeficiency virus (HIV) infection. Asymptomatic positive serology is not exclusionary.
- •Other concurrent immunotherapy (eg, immunosuppressants or chronic use of systemic corticosteroids, with the exception that low-dose corticosteroids [50 mg/day prednisone or equivalent corticosteroid] are allowed; these should be discussed with the Medical Monitor)
- •Known allergic reaction to a prior monoclonal antibody therapy or have any documented Anti-Drug Antibody (ADA) response; additionally known allergic reaction to the concomitant chemotherapies selected by the investigator for planned treatment in this study unless desensitization is planned
- •Previous treatment with farletuzumab or other folate receptor targeting agents
- •Previous treatment with cancer vaccine therapy
- •For subjects being enrolled to receive PLD plus carboplatin, prior treatment with anthracyclines or anthracenodiones
- •Breast-feeding, pregnant, or likely to become pregnant during the study
- •Any medical or other condition that, in the opinion of the investigator, would preclude the subject's participation in a clinical study including medical contraindications as outlined in the product labels for the chemotherapies selected by the investigator for planned treatment in this study
- •Patients who have had secondary debulking surgery or any second line therapy
- •Currently enrolled in another clinical study or used any investigational drug or device within 30 days (or 5 x half-life for investigational drugs where the half-life is known) preceding informed consent
研究组 & 干预措施
Farletuzumab
All participants will receive a loading dose for the first 2 weeks of 10 milligram per kilogram (mg/kg) farletuzumab, followed by 5 mg/kg weekly farletuzumab administered intravenously (IV).
干预措施: Farletuzumab (Drug)
Placebo
All subjects will receive placebo weekly, administered intravenously (IV).
干预措施: Placebo (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: From the date of randomization to the date of first documentation of PD, or date of death, whichever occurs first up to approximately 5 years 5 months
PFS was defined as the time (in months) from the date of randomization of a participant to the date of first observation of progression or date of death, whatever the cause. PFS was assessed based on the investigators' assessments utilizing Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Disease progression (PD) was defined as at least a 20 percent (%) increase or 5 millimeter (mm) increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.
次要结局
- Overall Survival (OS)(From the date of randomization until the date of death (up to approximately 5 years 5 months))
- Number of Participants With Best Overall Response (BOR)(From first dose of study drug (Baseline) up to approximately 5 years 5 months)
- Time to Tumor Response (TTR)(From the date of randomization until date of first observation of response (CR or PR) up to approximately 5 years 5 months)
- Duration of Response (DOR)(From date of the first observation of CR or PR until the date of first observation of progression or date of death up to approximately 5 years 5 months)
- Percentage of Participants Achieving Each Second Platinum-Free Interval Stratified by First Platinum-Free Interval(From the date of randomization to the date of first relapse (or first observation of progression/death) up to approximately 5 year 5 months)