A Phase 1b/2a, Multicenter, Open Label Study of the Safety, Efficacy and Pharmacokinetics of Narmafotinib in Combination With Modified FOLFIRINOX in Pancreatic Cancer Patients
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 67
- 试验地点
- 3
- 主要终点
- Number of Participants with Treatment-Emergent Adverse Events (TEAEs) from Baseline to End of Study
研究概览
简要总结
This study is testing narmafotinib, a type of drug called a focal adhesion kinase (FAK) inhibitor, when it is given in combination with 4 chemotherapy drugs in a regimen called FOLFIRINOX, to patients who have pancreatic cancer which has metastasised (spread). The study is being run in 2 parts.
Part A will test increasing dose levels of narmafotinib in at least 3 people per dose at up to 4 dose levels to assess safety.
Part B will test 2 of the dose levels from Part A in 20 people per dose, to select the best dose to take forward into future studies.
Participants will take narmafotinib as oral capsules every day. They will also receive mFOLFIRINOX chemotherapy on Day 1 and and Day 15 of 28-day cycles.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Aged at least 18 years at the time of consent.
- •Confirmed diagnosis of metastatic pancreatic adenocarcinoma (PDAC) within the 6 weeks prior to study start and have not received treatment for metastatic PDAC.
- •Have measurable disease by RECIST v1.
- •Eligible for treatment with mFOLFIRINOX as standard of care therapy.
- •Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1
- •Have a life expectancy of > 3 months.
- •Adequate organ function
- •Agree to use effective contraception.
排除标准
- •Pregnant or breast-feeding
- •Have received any investigational medicinal product (IMP) within 30 days or 5 half-lives (whichever is longer) prior to Day -
- •Neuroendocrine or acinar cell pancreas tumors.
- •Known brain metastases.
- •Conditions that could interfere with the swallowing or absorption of study medication.
- •Received previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease.
- •Received cytotoxic doses of any 5-FU based chemotherapy.
- •Any chemotherapy related toxicities greater than grade 1 from prior neoadjuvant or adjuvant therapy for PDAC.
- •Human immunodeficiency virus (HIV) infection and/or history of Hepatitis B infection or known to have active hepatitis B or C.
- •Uncontrolled angina, myocardial infarction, coronary stenting, stroke, or cerebrovascular accident within 1-year prior to the first dose of study drug.
- •History of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis.
- •Clinical signs of active infection at the time of Screening or Baseline.
- •Clinically significant allergies to narmafotinib, mFOLFIRINOX components (or any of their excipients) that are not likely to be well controlled with pre-medication or other supportive measures.
- •Any of the conditions or events outlined in the Contraindications or Special Warnings and Precautions sections of the mFOLFIRINOX component package inserts.
- •Peripheral neuropathy > Grade
- •Prior treatment with narmafotinib or other FAK inhibitor within the 2 years prior to screening.
研究组 & 干预措施
Part A
Part A is a phase 1b dose-escalation design that will enrol at least 3 participants in each of 4 dose-level cohorts, to determine 2 doses of narmafotinib to be explored in Part B.
干预措施: narmafotinib ascending doses (Drug)
Part B
Part B will determine the efficacy of 2 doses of narmafotinib selected from Part A
干预措施: narmafotinib dose comparison (Drug)
结局指标
主要结局
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) from Baseline to End of Study
时间窗: From first dose of study drug to end of study, an expected average of 6 months
TEAEs during study treatment and follow up periods
Part B: identification of optimal dose of narmafotinib
时间窗: From first dose of study drug to end of study, an expected average of 6 months
The optimal dose will be selected based on a review of safety, pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and any other available relevant data
次要结局
- Overall response rate (ORR)(Imaging every 56 days per participant, with an expected average duration of 6 months)
- Overall survival (OS)(Imaging every 56 days per participant, with an expected average duration of 6 months)
- Progression free survival (PFS)(Imaging every 56 days per participant, with an expected average duration of 6 months)
- Clinical benefit rate (CBR)(Imaging every 56 days per participant, with an expected average duration of 6 months)
- Duration of response (DOR)(Imaging every 56 days per participant, with an expected average duration of 6 months)
- Disease control rate (DCR)(Imaging every 56 days per participant, with an expected average duration of 6 months)
- narmafotinib levels in plasma(Days -7, -6, -1, 1 and 15 of Run-In/Cycle 1; and Day 1 of Cycles 2 and 4 (each cycle is 28 days))