An Open-label, Dose-finding, Phase Ib/II Study to Assess the Safety, Tolerability of JPI-547, a Dual Inhibitor of PARP/Tankyrase, in Combination With Modified FOLFIRINOX (mFOLFIRINOX) or Gemcitabine-nab-paclitaxel (GemAbraxne) in Patients With Locally Advanced and Metastatic Pancreatic Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 71
- 试验地点
- 4
- 主要终点
- Maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D).
研究概览
简要总结
The purpose of this study is to assess the safety, tolerability and efficacy of JPI-547 in combination with modified FOLFIRINOX (mFOLFIRINOX) or Gemcitabine-nab-paclitaxel (GemAbraxne) in patients with locally advanced and metastatic pancreatic cancer
详细描述
In combination with JPI-547 and chemotherapy in patients with locally advanced/metastatic pancreatic cancer,
Primary Objectives
- To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D).
- To select the optimal combination chemotherapy based on the safety profile.
Secondary Objectives
- To assess the safety and toxicity.
- To evaluate anti-tumor activity.
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
- 19 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •[Phase 1b/2]
- •Histologically or cytologically confirmed inoperable locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC)
- •Those with at least one measurable lesion in accordance with RECIST 1.1
- •Those with Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Those with an expected survival period ≥12 weeks
- •Patients with adequate hematologic function, renal and hepatic function confirmed by the following criteria (During the screening period, laboratory tests can be retested only once.)
- •Those who voluntarily decide to participate in this clinical study after hearing sufficient explanations and who consent in writing
- •[only to Phase 2]
- •1. Subjects from whom tumor tissue samples can be obtained at screening and who meet at least one of the following criteria:
- •Tumor tissue samples stored prior to screening are available
- •Tumor tissue samples can be obtained at screening with the subject's consent to biopsy
排除标准
- •[Phase 1b/2]
- •Those with a history of severe hypersensitivity to the investigational product or combination anticancer drugs.
- •Those with the following medical history or surgical history/procedural history confirmed
- •Other primary malignant tumors other than pancreatic cancer
- •Major surgery that requires general anesthesia or breathing aid
- •Severe cardiovascular disease
- •New York Heart Association Class 3 or 4 heart failure
- •Severe cerebrovascular disease t
- •Pulmonary thrombosis, deep vein thrombosis, or bronchial asthma, obstructive pulmonary disease, and other life-threatening severe lung diseases
- •Infections requiring administration of systemic antibiotics or antivirals, etc.
- •Hematologic malignancy
- •Those with the following diseases
- •Massive ascites, pleural effusions requiring therapeutic paracentesis
- •Neuropathy ≥Grade 2
- •Diarrhea, chronic inflammatory bowel disease
- •Intestinal paralysis, intestinal obstruction
- •Diseases that make oral administration difficult or affect absorption
- •Interstitial lung disease, pulmonary fibrosis
- •Dialysis patient
- •Patients with clinically significant symptoms or uncontrolled central nervous system or brain metastases
- •j. Uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic blood pressure >90 mmHg) k. Bleeding diatheses l. Active hepatitis B or C virus. m. Known human immunodeficiency virus (HIV) positive
- •Those with a medication history of the following drugs
- •Anti-cancer drug therapy such as chemotherapy and biological therapy
- •Radiation therapy within 2 weeks of baseline
- •Those who are taking or expected to require administration of strong inhibitors or inducers of CYP3A4
- •(For mFOLFIRINOX cohort) Those who are taking or expected to require administration of sorivudine
- •Patients who require continuous administration of non-steroidal anti-inflammatory drugs (NSAIDs) with high bleeding risk
- •Patients requiring continuous administration of systemic corticosteroid equivalent to prednisone >10 mg/day
- •Those who have received antithrombotic agents, including antiplatelet agents, anticoagulants, etc.
- •Pregnant women, lactating women, or women of childbearing potential and men who do not intend to practice abstinence or use appropriate contraceptive methods for until 6 months for men and 9 months for women after administration of the investigational product and during the clinical study
- •Those who have administered other investigational products or have received investigational medical device procedures within 4 weeks of the baseline
- •Other patients who are inappropriate or unable to participate in this clinical study at the discretion of the investigator
研究组 & 干预措施
Arm B (GemAbraxane)
JPI-547 and Combination Chemotherapy (Gemcitabine-nab-paclitaxel) The study is conducted in a 3+3 dose escalation method.
干预措施: JPI-547 (Drug)
Arm B (GemAbraxane)
JPI-547 and Combination Chemotherapy (Gemcitabine-nab-paclitaxel) The study is conducted in a 3+3 dose escalation method.
干预措施: Gemcitabine-nab-paclitaxel (Drug)
Arm A (mFOLFIRINOX)
JPI-547 and Combination Chemotherapy(mFOLFIRINOX) The study is conducted in a 3+3 dose escalation method.
干预措施: modified FOLFIRINOX (Drug)
Arm A (mFOLFIRINOX)
JPI-547 and Combination Chemotherapy(mFOLFIRINOX) The study is conducted in a 3+3 dose escalation method.
干预措施: JPI-547 (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D).
时间窗: From the date of administration to 4 weeks (DLT period)
The MTD is determined according to the traditional 3+3 rule-based method for each combination therapy, and it is defined as the highest dose with a DLT incidence of less than 1/3 or 2/6 subjects.
Phase 1b: Maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D).
时间窗: From the date of administration to 4 weeks (DLT period)
The MTD is determined according to the traditional 3+3 rule-based method for each combination therapy, and it is defined as the highest dose with a DLT incidence of less than 1/3 or 2/6 subjects.
Phase 2: To determine the regimen of JPI-547 in combination with Chemotherapy GemAbraxane and to evaluate the potential antitumor activity and safety of the combination therapy.
时间窗: From first dose until disease progression, assessed up to end of study
次要结局
- To assess the adverse events, drug adverse events, and serious adverse events evaluated by NCI-CTCAE v5.0(Until 4 weeks after the last dose administration)
- To evaluate anti-tumor activity.(Evaluation at 8 weeks intervals through study completion from the date of study entry until the date of progression, up to 18 months)