A Phase 1b/2 Study of OMP-59R5 in Combination With Nab-Paclitaxel and Gemcitabine in Subjects With Previously Untreated Stage IV Pancreatic Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 217
- 试验地点
- 26
- 主要终点
- Phase 2: Overall Survival (ITT Population)
研究概览
简要总结
The study consists of a Phase1b lead-in portion to determine the maximum tolerated dose (MTD) of OMP-59R5 in combination with nab-paclitaxel and gemcitabine followed by a Phase 2, multicenter, randomized, placebo-controlled portion to evaluate the efficacy and safety of OMP-59R5 in combination with nab-paclitaxel and gemcitabine in subjects with previously untreated stage IV pancreatic 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 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must meet all of the following major inclusion criteria to be eligible for the study:
- •18 years of age or older
- •Histologically or cytologically documented stage IV ductal adenocarcinoma of the pancreas.
- •Performance Status (ECOG) 0 or 1
- •FFPE tumor tissue from metastatic site(s
- •Adequate organ function
- •Written consent on an IRB/IEC-approved Informed Consent Form prior to any study-specific evaluation.
- •For women of child-bearing potential, negative serum pregnancy test at screening and use of physician-approved method of birth control from 30 days prior to the first study drug administration to 30 days following the last study drug administration.
- •Male subjects must be surgically sterile or must agree to use physician-approved contraception from 30 days prior to the first study drug administration to 30 days following the last study drug administration.
排除标准
- •Subjects who meet any of the following major exclusion criteria will not be eligible for participation in the study:
- •Neuroendocrine tumors (i.e., carcinoid, islet cell cancer) of the pancreas.
- •Known brain metastases.
- •Prior therapy, including systemic therapy, surgical resection or radiation for newly diagnosed stage IV pancreatic cancer.
- •Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g., substance abuse, uncontrolled intercurrent illness including active infection, arterial thrombosis, symptomatic pulmonary embolism).
- •Any disorder that would significantly compromise protocol compliance.
- •Prior non-pancreatic malignancy treated with chemotherapy. Prior malignancies treated with surgery and/or radiotherapy alone must be in remission ≥3 years. The following prior malignancies are allowable irrespective of when they occurred: in situ carcinoma of the cervix, in situ ductal breast cancer, low-grade local bladder cancer, and nonmelanotic skin cancer.
- •Known human immunodeficiency virus (HIV) infection.
- •Females who are pregnant or breastfeeding.
研究组 & 干预措施
Gemcitabine and Nab-Paclitaxel plus Placebo
Gemcitabine and Nab-Paclitaxel plus Placebo
干预措施: Placebo (Drug)
Gemcitabine and Nab-Paclitaxel plus Placebo
Gemcitabine and Nab-Paclitaxel plus Placebo
干预措施: Nab-Paclitaxel (Drug)
OMP-59R5 plus Gemcitabine and Nab-Paclitaxel
OMP-59R5 plus Gemcitabine and Nab-Paclitaxel
干预措施: OMP-59R5 (Drug)
OMP-59R5 plus Gemcitabine and Nab-Paclitaxel
OMP-59R5 plus Gemcitabine and Nab-Paclitaxel
干预措施: Gemcitabine (Drug)
OMP-59R5 plus Gemcitabine and Nab-Paclitaxel
OMP-59R5 plus Gemcitabine and Nab-Paclitaxel
干预措施: Nab-Paclitaxel (Drug)
Gemcitabine and Nab-Paclitaxel plus Placebo
Gemcitabine and Nab-Paclitaxel plus Placebo
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Phase 2: Overall Survival (ITT Population)
时间窗: Up to 1 year in absence of unacceptable toxicity or disease progression.
To determine the clinical benefit, as measured by overall survival (OS) ofthe addition of OMP-59R5 to nab-paclitaxel and gemcitabine in all subjects who are receiving first-line therapy for stage IV pancreatic cancer.
Phase Ib: Number of Participants With Dose-limiting Toxicities (DLT)
时间窗: Up to 1 year in absence of unacceptable toxicity or disease progression.
Number of participants with dose-limiting toxicities when administered OMP-59R5 every of other week (Days 1 and 15) in combination with nab-paclitaxel (Nab-P) 125 mg/m2 and gemcitabine (Gem) 1000 mg/m2 on Days 1, 8, and 15 of every 28-day cycle in subjects with previously untreated stage IV pancreatic cancer. In the event that no DLTs are observed, maximum tested dose would be considered the Maximum Tolerated Dose (MTD).
Phase 2: Median OS by Notch 3 Percentile (ITT Population)
时间窗: Up to 1 year in absence of unacceptable toxicity or disease progression.
To determine the clinical benefit, as measured by OS of the addition of OMP-59R5 to Nab-P+Gem across the 4 subject subsets: subjects with Notch3 ≥ 25th percentile, subjects with Notch3 ≥ 50th percentile, subjects with Notch3 ≥ 75th percentile and all subjects receiving first-line therapy for stage IV pancreatic cancer with Notch3 high expression level.
次要结局
未报告次要终点