A Phase 1b/2 Randomized, Controlled Study of AVB-S6-500 in Combination With Pegylated Liposomal Doxorubicin (PLD) or Paclitaxel (Pac) in Patients With Platinum-resistant Recurrent Ovarian Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 53
- 试验地点
- 16
- 主要终点
- Incidence of Adverse Events (AEs)
研究概览
简要总结
This is a Phase 1b/2 study of AVB-S6-500 in combination with pegylated liposomal doxorubicin (PLD) or paclitaxel (Pac) in patients with platinum resistant recurrent ovarian cancer. The phase 1b portion of the study is open label and patients will receive either AVB-S6-500+PLD or AVB-S6-500+ Pac. The Phase 2 portion of the study is randomized, double-blind, placebo-controlled study to compare efficacy and tolerability of AVB-S6-500 in combination with PLD or Pac versus placebo plus PLD or Pac.
详细描述
While this study was planned as two-part study consisting of a Phase 1b and a Phase 2 portion, the sponsor decided not to proceed with the Phase 2 portion.
The Phase 1b portion of the study was a multicenter, 2-group, open-label design to evaluate the safety and tolerability of AVB-S6-500 combined with PLD or Pac in subjects with platinum-resistant recurrent ovarian cancer. The decision to enroll in the Phase 2 portion of the study was to be driven by the recommendation of a safe and tolerable dose of AVB-S6-500 in combination with each chemotherapy backbone; however, enrollment into the Phase 2 portion was not initiated per Sponsor decision. Given that sufficient data were obtained in the Phase 1b portion AVB-S6-500 + Pac group, the decision was made to pursue a randomized Phase 3 to further study the benefit of this combination versus paclitaxel alone in patients with platinum resistant ovarian cancer.
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
- •Age 18 years or older
- •Histologically confirmed and documented recurrent ovarian, fallopian tube, and peritoneal cancer.
- •Platinum resistant disease, defined as progression within ≤ 6 months from completion of most recent regimen and calculated from the date of the last administered dose of platinum therapy
- •Must have available archived tumor tissue OR if archived tissue is not available, willing to provide a fresh tumor biopsy
- •Must have radiologic imaging with a computerized tomography (CT) scan or magnetic resonance imaging (MRI) within 4 weeks of first dose of study drug
- •Received at least 1 but not more than 3 therapy regimens, not including maintenance or adjuvant therapy
- •Must have ovarian cancer that is measurable according to RECIST 1.1
- •ECOG performance status of 0-1
- •Normal gastrointestinal (GI), bone marrow, liver and kidney function
- •At least 28 days between termination of prior anti-cancer or hormonal therapy and administration of AVB-S6-500
排除标准
- •Primary platinum-refractory disease (defined as progression during the first platinum regimen or within 4 weeks of completion of the first platinum regimen)
- •Currently being treated with concurrent anti-cancer therapy or any other interventional treatment or trial
- •Received prior therapy with Pac or PLD in the recurrent setting, depending on physician-chosen chemotherapy for this study
- •Significant cardiac disease history
- •Has other prior or concurrent malignancy within the past 5 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix
- •Symptomatic CNS metastasis or metastases
- •Serious active infection requiring IV antibiotics and/or hospitalization at study entry
- •Has known previous or current human immune deficiency (HIV) syndrome, hepatitis B, or hepatitis C
- •Has had paracentesis for ascites within 3 months
研究组 & 干预措施
Phase 1b: AVB-S6-500+PLD
干预措施: AVB-S6-500 (Drug)
Phase 1b: AVB-S6-500+PLD
干预措施: Pegylated liposomal doxorubicin (PLD) (Drug)
Phase 1b: AVB-S6-500+Pac
干预措施: AVB-S6-500 (Drug)
Phase 1b: AVB-S6-500+Pac
干预措施: Paclitaxel (Pac) (Drug)
Phase 2: AVB-S6-500+PLD
干预措施: AVB-S6-500 (Drug)
Phase 2: AVB-S6-500+PLD
干预措施: Pegylated liposomal doxorubicin (PLD) (Drug)
Phase 2: AVB-S6-500+Pac
干预措施: AVB-S6-500 (Drug)
Phase 2: AVB-S6-500+Pac
干预措施: Paclitaxel (Pac) (Drug)
Phase 2: Placebo+PLD
干预措施: Pegylated liposomal doxorubicin (PLD) (Drug)
Phase 2: Placebo+PLD
干预措施: Placebo (Other)
Phase 2: Placebo+Pac
干预措施: Paclitaxel (Pac) (Drug)
Phase 2: Placebo+Pac
干预措施: Placebo (Other)
结局指标
主要结局
Incidence of Adverse Events (AEs)
时间窗: 6 months
Measured by the number of patients with AEs in Phase 1 portion of the study.
Anti-tumor activity of AVB-S6-500 in combination with Pac
时间窗: 18 months
Measured by progression free survival (PFS) in patients receiving AVB-S6-500+ Pac versus patients receiving Placebo+Pac in Phase 2 portion of the study.
Anti-tumor activity of AVB-S6-500 in combination with PLD
时间窗: 18 months
Measured by progression free survival (PFS) in patients receiving AVB-S6-500+PLD versus patients receiving Placebo+PLD in Phase 2 portion of the study.
次要结局
- Pharmacokinetics: Tmax(18 months)
- Duration of response (DOR)(18 months)
- Overall survival(30 months)
- Pharmacokinetics: AUC(18 months)
- Pharmacokinetics: t1/2(18 months)
- Anti-drug antibody (ADA) titers(18 months)
- Quality of Life(QOL)(18 months)
- Pharmacokinetics: Cmax(18 months)
- Pharmacodynamic marker assessment(18 months)
- Objective response rate(18 months)
- Disease control rate(18 months)
- CA-125 response rate(18 months)