A Phase 1b Study Evaluating Momelotinib Combined With Capecitabine and Oxaliplatin in Subjects With Relapsed/Refractory Metastatic Pancreatic Ductal Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 16
- 试验地点
- 4
- 主要终点
- Incidence of dose limiting toxicities
研究概览
简要总结
This study will evaluate the safety, tolerability, and define the maximum tolerated dose (MTD) of momelotinib (MMB) combined with capecitabine and oxaliplatin in adults with relapsed/refractory metastatic pancreatic ductal adenocarcinoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- All
- 接受健康志愿者
- 否
入选标准
- •Relapsed or refractory metastatic pancreatic adenocarcinoma
- •Received 1 prior chemotherapy regimen for metastatic pancreatic ductal adenocarcinoma (not including neoadjuvant and/or adjuvant therapy)
- •Measurable disease per RECIST v1.1
- •Adequate organ function defined as
- •Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x upper limit of normal (ULN) OR ≤ 5 x ULN if liver metastases are present; total conjugated bilirubin ≤ 2 x ULN
- •Absolute neutrophil count (ANC) ≥1500 cells/mm^3, platelet ≥100,000 cells/mm^3, hemoglobin ≥ 9.0 g/dL
- •Creatinine clearance (CrCl) > 50 ml/min as calculated by the Cockroft-Gault method
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
排除标准
- •Received more than 1 prior line of chemotherapy for metastatic pancreatic ductal adenocarcinoma
- •Major surgery within 21 days of first dose of study drug
- •Minor surgical procedure(s) within 7 days of enrollment or not yet recovered from prior minor surgery (placement of central venous access device, fine needle aspiration, or endoscopic biliary stent ≥ 1 day before enrollment is acceptable)
- •Chemotherapy, immunotherapy, biologics, and/or investigational therapy within 21 days prior to first dose of study drug
- •Known positive status for HIV, chronic active or acute viral hepatitis A, B, or C infection, or hepatitis B or C carrier
- •Known dihydropyrimidine dehydrogenase deficiency
- •Peripheral neuropathy ≥ Grade 2
- •Any condition that impairs gastrointestinal absorption of drug
- •Known or suspected brain or central nervous system metastases
- •Diagnosis of pancreatic islet neoplasm, acinar cell carcinoma, non-adenocarcinoma, adenocarcinoma originating from the biliary tree or cystadenocarcinoma
- •External biliary drain
- •Documented myocardial infarction or unstable/uncontrolled cardiac disease within 6 months of enrollment
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Momelotinib (MMB)+capecitabine
Participants will receive momelotinib (MMB)+capecitabine at varying dose levels to determine the MTD for momelotinib (MMB) and capecitabine.
干预措施: Momelotinib (MMB) (Drug)
Momelotinib (MMB)+capecitabine
Participants will receive momelotinib (MMB)+capecitabine at varying dose levels to determine the MTD for momelotinib (MMB) and capecitabine.
干预措施: Capecitabine (Drug)
Momelotinib (MMB)+capecitabine+oxaliplatin
Upon reaching the MTD for momelotinib (MMB) and capecitabine or if no MTD is reached, participants will receive momelotinib (MMB)+capecitabine at the MTD plus oxaliplatin at varying dose levels to determine the MTD of combination capecitabine, momelotinib (MMB), and oxaliplatin.
干预措施: Momelotinib (MMB) (Drug)
Momelotinib (MMB)+capecitabine+oxaliplatin
Upon reaching the MTD for momelotinib (MMB) and capecitabine or if no MTD is reached, participants will receive momelotinib (MMB)+capecitabine at the MTD plus oxaliplatin at varying dose levels to determine the MTD of combination capecitabine, momelotinib (MMB), and oxaliplatin.
干预措施: Capecitabine (Drug)
Momelotinib (MMB)+capecitabine+oxaliplatin
Upon reaching the MTD for momelotinib (MMB) and capecitabine or if no MTD is reached, participants will receive momelotinib (MMB)+capecitabine at the MTD plus oxaliplatin at varying dose levels to determine the MTD of combination capecitabine, momelotinib (MMB), and oxaliplatin.
干预措施: Oxaliplatin (Drug)
结局指标
主要结局
Incidence of dose limiting toxicities
时间窗: Up to 21 days
Dose limiting toxicities refer to toxicities experienced during the first 21 days of treatment that have been judged to be clinically significant and at least possibly related to study treatment.
Incidence of adverse events, assessment of clinical laboratory test findings, physical examination, 12-lead electrocardiogram (ECG), and vital signs measurements
时间窗: Up to 2 years
This composite endpoint will measure the safety profile of momelotinib.
次要结局
- Progression-free survival(Up to 2 years)
- Pharmacokinetic (PK) profile of momelotinib (MMB)(Predose and postdose on Day 15)
- Overall response rate(Up to 2 years)
- Overall survival(Up to 2 years)