A Phase 3, Randomized, Double-blind, Placebo-controlled Study of Gemcitabine and Nab-paclitaxel Combined With Momelotinib in Subjects With Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma Preceded by a Dose-finding, Lead-in Phase
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 25
- 试验地点
- 4
- 主要终点
- Lead-In Phase: Percentage of Participants Experiencing Treatment-Emergent Dose Limiting Toxicity (DLT) Adverse Events
研究概览
简要总结
There will be two phases to this study. The lead-in phase will evaluate the safety, pharmacokinetics, and define the maximum tolerated dose (MTD) of momelotinib (MMB) combined with nab-paclitaxel and gemcitabine (nab-P + G) in adults with previously untreated metastatic pancreatic ductal adenocarcinoma. The randomized treatment phase will evaluate the efficacy, safety, and tolerability of nab-P + G with either MMB administered at the MTD or placebo in adults with previously untreated metastatic pancreatic ductal adenocarcinoma. Participants will continue study treatment until disease progression, unacceptable toxicity, consent withdrawal, or participant's refusal of treatment. Following treatment, participants will be followed for safety for 30 days and for survival approximately every 3 months for up to 3 years.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Presence of metastatic pancreatic adenocarcinoma plus 1 of the following:
- •Histological diagnosis of pancreatic adenocarcinoma confirmed pathologically, OR
- •Pathologist confirmed histological/cytological diagnosis of adenocarcinoma consistent with pancreas origin in conjunction with either:
- •The presence of a mass in the pancreas, OR
- •A history of resected pancreatic adenocarcinoma
- •Measurable disease per RECIST v1.1
- •Adequate organ function defined as follows:
- •Total bilirubin ≤ 1.25 x upper limit of the normal range (ULN); aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN
- •Absolute neutrophil count (ANC) > 1500 cells/mm^3, platelet > 100,000 cells/mm^3, hemoglobin > 9 g/dL
- •Serum creatinine < ULN OR calculated creatinine clearance (CrCl) of ≥ 60 ml/min
- •Eastern Cooperative Oncology Group (ECOG ) 0 or 1
- •Modified Glasgow prognostic score (mGPS) of 1 or 2 at Screening (randomized phase only)
排除标准
- •Neoadjuvant or adjuvant chemotherapy or chemoradiotherapy for pancreatic adenocarcinoma
- •Currently or previously treated with biologic, small molecule, immunotherapy, chemotherapy, or other agents for metastatic pancreatic carcinoma
- •Major surgery within 28 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)
- •Known positive status for HIV
- •Chronic active or acute viral hepatitis A, B, or C infection (testing required for hepatitis B and C), or hepatitis B or C carrier
- •Peripheral neuropathy ≥ Grade 2
- •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
- •History of interstitial pneumonitis and/or require supplemental oxygen therapy
- •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
Participants will receive momelotinib plus nab-paclitaxel and gemcitabine.
干预措施: Momelotinib (Drug)
Momelotinib
Participants will receive momelotinib plus nab-paclitaxel and gemcitabine.
干预措施: Nab-paclitaxel (Drug)
Momelotinib
Participants will receive momelotinib plus nab-paclitaxel and gemcitabine.
干预措施: Gemcitabine (Drug)
Placebo
Participants will receive placebo to match momelotinib plus nab-paclitaxel and gemcitabine.
干预措施: Placebo to match momelotinib (Drug)
Placebo
Participants will receive placebo to match momelotinib plus nab-paclitaxel and gemcitabine.
干预措施: Nab-paclitaxel (Drug)
Placebo
Participants will receive placebo to match momelotinib plus nab-paclitaxel and gemcitabine.
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Lead-In Phase: Percentage of Participants Experiencing Treatment-Emergent Dose Limiting Toxicity (DLT) Adverse Events
时间窗: Up to 28 Days
Dose limiting toxicities were based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Dose limiting toxicities referred to toxicities experienced during the first 28 days (Cycle 1) of treatment that were judged to be clinically significant and related to study treatment. No statistical analysis was planned or performed for this endpoint.
Randomized Treatment Phase: Overall Survival (OS)
时间窗: Baseline up to the Date of Death or Censoring, up to 3 years
Overall survival was defined as the time interval from first dose date of MMB to death from any cause
次要结局
- Lead-In Phase: Progression-Free Survival (PFS)(Baseline up to the Date of Event or Censoring, up to 3 years)
- Lead-In Phase: Overall Survival (OS)(Baseline up to the Date of Death or Censoring, up to 3 years)
- Lead-In Phase: Overall Response Rate (ORR)(Baseline up to the Last Tumor Assessment Date, up to 3 years)
- Randomized Treatment Phase: Progression-Free Survival (PFS)(Baseline up to the Date of Event or Censoring, up to 3 years)
- Randomized Treatment Phase: Overall Response Rate(Baseline up to the Last Tumor Assessment Date, up to 3 years)