A Phase 1b Dose Escalation Study of OMP-54F28 in Combination With Nab-Paclitaxel and Gemcitabine in Patients 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
- 26
- 试验地点
- 5
- 主要终点
- Safety and tolerability of OMP-54F28 in combination with nab-paclitaxel and gemcitabine in patients with previously untreated Stage IV pancreatic cancer
研究概览
简要总结
This is an open-label Phase 1b dose-escalation study to assess the safety, tolerability, and PK of OMP-54F28 when combined with nab-paclitaxel and gemcitabine. OMP-54F28 will be administered IV on Days 1 and 15 of each 28-day cycle. Nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) will be administered IV on Days 1, 8, and 15 of each cycle. The planned dose levels of OMP-54F28 are 3.5 mg/kg and 7.0 mg/kg.
详细描述
Depending on safety in this study, additional lower or intermediate dose levels may be evaluated. Depending on emerging safety data from the Phase 1a study 54F28-001 with continuing dose escalation, additional higher dose levels of OMP-54F28 may be evaluated in this study. No dose escalation of OMP-54F28 will be allowed within a dose cohort.
Once the maximum tolerated dose (MTD) or maximum administered dose (MAD) has been determined, up to 10 patients may be enrolled in the cohort-expansion phase to better characterize the safety, tolerability and PK of OMP-54F28 combined with nab-paclitaxel and gemcitabine. Up to approximately 34 patients may be enrolled into the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Signed Informed Consent Form
- •Age ≥18 years
- •Histologically documented Stage IV ductal adenocarcinoma of the pancreas
- •Availability of FFPE tumor tissue, either archival or obtained at study entry through fresh biopsy
- •Tumor tissue from fine needle aspiration is not acceptable.
- •ECOG performance status of 0 or 1
- •Adequate hematologic and end-organ function
- •Evaluable or measurable disease per RECIST v1.1
- •For women of childbearing potential and men with partners of childbearing potential, agreement to use two effective forms of contraception
排除标准
- •Prior therapy before Day 1 of Cycle 1 for the treatment of Stage IV pancreatic cancer
- •Prior adjuvant therapy for the treatment of ductal adenocarcinoma of the pancreas
- •Known hypersensitivity to any component of study treatments
- •Known brain metastases, uncontrolled seizure disorder, or active neurologic disease
- •Leptomeningeal disease as a manifestation of cancer
- •Active infection requiring antibiotics
- •Bisphosphonate therapy for symptomatic hypercalcemia
- •Known history of clinically significant liver disease, including active viral hepatitis and cirrhosis
- •Significant intercurrent illness including, but not limited to, unstable angina pectoris, and cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements
- •Pregnancy, lactation, or breastfeeding
- •Known HIV infection
- •Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
- •Concurrent use of therapeutic warfarin
- •History of interstitial lung disease, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or pulmonary hypersensitivity pneumonitis
- •New York Heart Association Classification III or IV
- •Known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the first dose of study treatment or anticipation of need for major surgical procedure during the course of the study
- •Osteoporosis based on a T-score of <-2.5 at the left or right total hip, left or right femoral neck or lumbar spine (L1-L4) as determined by DEXA scan
- •Bone metastases and one of the following:
- •Prior history of a pathologic fracture
- •Lytic lesion requiring an impending orthopedic intervention
- •Lack of treatment with a bisphosphonate or denosumab
- •Treatment with a thiazolidinedione PPAR gamma inhibitor; e.g. Actos® (pioglitazone) and Avandia® (rosiglitazone)
- •Active treatment with an oral or IV glucocortocoid for ≥4 weeks at a daily dose equivalent to or greater than 7.5 mg of oral prednisone
- •Fasting β-CTX of >1000 pg/mL
- •Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia
研究组 & 干预措施
Drug: OMP-54F28, Nab-Paclitaxel and Gemcitabine
干预措施: OMP-54F28, Nab-Paclitaxel and Gemcitabine (Drug)
结局指标
主要结局
Safety and tolerability of OMP-54F28 in combination with nab-paclitaxel and gemcitabine in patients with previously untreated Stage IV pancreatic cancer
时间窗: Subjects will be treated and observed for DLT through the end of the first cycle (from Day 0 - 28)
The maximum tolerated dose (MTD) will be determined in patients treated with gemcitabine in combination with weekly nab-paclitaxel (from Day 0 - 28)
次要结局
- Pharmacokinetics (PK) of OMP-54F28 when administered in combination with nabpaclitaxel and gemcitabine to patients with previously untreated Stage IV pancreatic cancer(Plasma sample for Pharmacokinetics (PK) analysis to be obtained prior to the gemcitabine infusion and before nabpaclitaxel infusion from Day 0 to treatment termination)