XB2001 联合 ONIVYDE + 5-FU/LV（+亚叶酸）治疗晚期胰腺癌 (1-BETTER)
一项 I/II 期随机、双盲、安慰剂对照试验 (1-BETTER) 检查 XB2001（抗 IL-1⍺ 真人抗体）与 ONIVYDE + 5-FU/LV（+亚叶酸）的高级组合胰腺癌
该试验将包括 2 个部分（第 1 阶段和第 2 阶段）。
第一部分将是 I 期、开放标签、剂量递增研究，以确定 XB2001 的最大耐受剂量 (MTD)，通过剂量限制毒性 (DLT) 与 ONIVYDE + LV + 5-FU 化疗方案相结合来衡量晚期胰腺癌患者，并确定后续 2 期研究的推荐剂量。
第 2 阶段部分将以 XB2001 的最大确定耐受剂量（ MTD ）实施。 第二阶段的目标招募是 60 名患者，他们将以 1：1 的比例随机分配到 XB2001加 ONIVYDE + LV + 5-FU（第 1 组）或安慰剂加 ONIVYDE + LV + 5-FU（第 2 组）。
研究概览
地位
条件
详细说明
研究标题：一项 I/II 期随机、双盲、安慰剂对照试验 (1-BETTER) 检查 XB2001（抗 IL-1⍺ 真人抗体）与 ONIVYDE + 5-FU/LV（+亚叶酸) 晚期胰腺癌
主办方：XBiotech USA, Inc.
研究主席：Benjamin Musher，医学博士
样本量：美国将招募大约 69 名患者（开放标签第 1 阶段部分至少有 9 名患者，随机第 2 阶段部分至少有 60 名患者）
大约持续时间：
该试验将包括 2 个阶段。 第一部分将是一项 I 期、开放标签、剂量递增研究，在至少九名接受 ONIVYDE + 亚叶酸 l + d 外消旋治疗的转移性胰腺癌患者中评估 XB2001 的安全性、耐受性并确定最大耐受剂量 (MTD) + 5-氟尿嘧啶化疗。 I 期部分每位患者的持续时间为 14 天（1 个治疗周期），在接受 ONIVYDE + 亚叶酸 l + d 外消旋 + 5-氟尿嘧啶化疗治疗之前，他们将接受一剂 XB2001 静脉注射，并评估剂量有限毒性 (DLT)。 第二阶段部分将在第一阶段部分完成并宣布 MTD 后实施。 受试者参与随机、双盲、安慰剂对照的 II 期试验的持续时间约为 28 周：包括长达 30 天的筛选期和 24 周的治疗期。 所有研究对象都可以在开放标签扩展中继续使用 XB2001 进行治疗，只要他们被判断为在临床上有益并且没有不可接受的毒性。
研究类型
注册 (实际的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习地点
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Arizona
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Tucson、Arizona、美国、85711
- Arizona Oncology Associates
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California
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Burbank、California、美国、91505
- Disney Family Cancer Center at Providence St. Joseph Medical Center
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Cerritos、California、美国、90703
- TOI Clinical Research
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Fullerton、California、美国、92835
- Providence St. Joseph Heritage - Fullerton, CA
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Newport Beach、California、美国、92663
- Hoag Memorial Hospital Presbyterian
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Colorado
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Grand Junction、Colorado、美国、81505
- Grand Valley Oncology
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Florida
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Lake Mary、Florida、美国、32746
- Sarah Cannon - Florida Cancer Specialists
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Miami Beach、Florida、美国、33140
- Mt. Sinai Comprehensive Cancer Center
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Sarasota、Florida、美国、34239
- Sarasota Memorial Hospital
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Weston、Florida、美国、33331
- Cleveland Clinic of Florida
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Indiana
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Goshen、Indiana、美国、46526
- Goshen Center for Cancer Care
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Kansas
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Merriam、Kansas、美国、66204
- Alliance for Multispecialty Research, LLC
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Louisiana
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New Orleans、Louisiana、美国、70121
- Ochsner Clinic Foundation
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Michigan
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Detroit、Michigan、美国、48201
- Barbara Ann Karmanos Cancer Institute
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Farmington Hills、Michigan、美国、48334
- Revive Research - Farmington Hills
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Sterling Heights、Michigan、美国、48126
- Revive Research - Sterling Heights
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Montana
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Billings、Montana、美国、59102
- St. Vincent Frontier Cancer Center
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New Jersey
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Florham Park、New Jersey、美国、07932
- Summit Medical Group
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New York
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Stony Brook、New York、美国、11794
- Stony Brook Cancer Center
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The Bronx、New York、美国、10461
- Montefiore Einstein Medical Center
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Oregon
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Portland、Oregon、美国、97213
- Providence Portland
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Pennsylvania
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Pittsburgh、Pennsylvania、美国、15232
- UPMC Hillman Cancer Center
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Tennessee
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Knoxville、Tennessee、美国、37920
- University of Tennessee Medical Center Cancer Institute
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Nashville、Tennessee、美国、37232
- Vanderbilt University
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Nashville、Tennessee、美国、37203
- Sarah Cannon - Tennessee Oncology
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Texas
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Arlington、Texas、美国、76012
- Texas Oncology - Arlington
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Dallas、Texas、美国、75230
- Mary Crowley Cancer Research
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Utah
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Ogden、Utah、美国、84405
- Community Cancer Trials of Utah
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Virginia
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Fairfax、Virginia、美国、22031
- Virginia Cancer Specialists
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Midlothian、Virginia、美国、23114
- Bon Secours St. Francis Cancer Center
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
描述
纳入标准：
- 经组织学或细胞学证实的转移性、不可切除或复发性胰腺外分泌腺癌
- 根据实体瘤反应评估标准 V1.1 至少有一个可测量的病灶
- 一种既往基于吉西他滨的疗法或一种 FOLFIRINOX 和吉西他滨联合疗法后记录的疾病进展
- 东部肿瘤协作组 (ECOG) 表现 0 或 1 或 Karnofsky 表现状态 (KPS) ≥ 70
- 足够的肝、肾和骨髓功能
排除标准：
- 在预期的首次剂量给药后 2 周内，体能状态（病历）出现临床显着下降
- 具有临床意义的胃肠道疾病
- 入组前不到 6 个月的严重动脉血栓栓塞事件
- 既往全脑放射治疗 (WBRT)
- 脑转移的证据
- NYHA III 级或 IV 级充血性心力衰竭、室性心律失常或血压失控（定义为 ≥ 160/100 mm Hg）
- 在访问 1/基线访问之前的 14 天内使用强 CYP3A4 诱导剂或抑制剂和/或 UGT1A1 抑制剂。
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：顺序分配
- 屏蔽：四人间
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：Phase I: Dose Escalation Phase
In Phase I (Dose escalation phase), 3 sequential dose levels were administered by participants; 250 mg (dose cohort 1), 500 mg (dose cohort 2), and 1000 mg (dose cohort 3), and traditional 3:3 design was used. Dose-escalation will continue if none of three subjects experience a dose-limiting toxicity (DLT). After enrollment participants received two treatment cycles (a total of 28 days) in which they were given one intravenous (IV) dose of XB2001 prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle. |
Subjects were administered one intravenous (IV) dose of XB2001 250 mg prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.
其他名称：
Subjects were administered one intravenous (IV) dose of XB2001 500 mg prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.
其他名称：
Subjects were administered one intravenous (IV) dose of XB2001 1000 mg prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.
其他名称：
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实验性的：Phase II: Dose Expansion Phase
In Phase II (dose expansion phase), participants were randomized in 1:1 fashion and received:
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Subjects were administered one intravenous (IV) dose of XB2001 1000 mg prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.
其他名称：
Subjects were administered one intravenous (IV) dose of placebo 1000 mg prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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To Establish the Maximum Tolerated Dose (MTD) of XB2001 as Measured by Dose-Limiting Toxicity (DLT), in Combination With ONIVYDE + LV + 5-FU Chemotherapy Regimen in Patients With Advanced Pancreatic Cancer.
大体时间：28 days (consisting of the first two 14-day treatment cycles or the formal DLT observation window).
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The primary objective of the Phase I portion is to identify the MTD of XB2001 when administered in combination with ONIVYDE + LV + 5-FU. The MTD is defined as the highest dose level at which no more than one out of six subjects experience a DLT. If two or more subjects in a cohort of six experience a DLT, the MTD is considered exceeded, and the previous lower dose level will be identified as the MTD. If no DLTs are observed at the highest dose level studied, that dose will be used for Phase II. A DLT is defined as any Grade 3-4 adverse event (per NCI CTCAE v5.0) occurring within the first 28 days that is deemed possibly related to the combination regimen, unless the toxicity is clearly attributable to a single non-XB2001 component. Specific DLT criteria include:
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28 days (consisting of the first two 14-day treatment cycles or the formal DLT observation window).
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Safety and Tolerability of XB2001 in Combination With ONIVYDE + LV + 5-FU
大体时间：From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
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This endpoint evaluates the cumulative safety profile and patient tolerance of XB2001 when administered at the Maximum Tolerated Dose (MTD) or the maximum dose studied in Phase I, in combination with the ONIVYDE + LV + 5-FU regimen. Safety is characterized by the total number of participants in each cohort who experienced one or more adverse events. For the purpose of this count, each participant is counted only once, regardless of the total number of individual adverse events experienced. |
From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Progression Free Survival (PFS)
大体时间：From baseline until the date of first documented disease progression or date of death (from any cause), whichever come first.
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Progression free survival (PFS) was defined as the time from randomization to first progression based on RECIST v1.1 criteria or death from any cause, whichever occurred first.
Subjects who had no baseline and post-baseline tumor assessment and no death, or no adequate post-baseline tumor assessment and no death were censored at the date of randomization.
Subjects alive and without documented disease progression at the time of data analysis are censored at the date of the last adequate tumor assessment.
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From baseline until the date of first documented disease progression or date of death (from any cause), whichever come first.
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Overall Survival (OS)
大体时间：From baseline until death from any cause
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OS was defined as the duration from the date of randomization until death irrespective of the cause.
Subjects who were alive at the time of analysis were censored at the last known date alive.
Subjects without any data after baseline were censored on the randomization day.
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From baseline until death from any cause
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Objective Response Rate (ORR)
大体时间：Analyses performed at Visit 5 (Week 8), Visit 9 (Week 16), and Visit 13 (Week 24). This outcome measure was reported for Visit 13.
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Objective Response Rate (ORR) is defined as the proportion of subjects in the Phase II Population who achieved a Best Overall Response (BOR) of either Complete Response (CR) or Partial Response (PR), as defined by RECIST v1.1 criteria.
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Analyses performed at Visit 5 (Week 8), Visit 9 (Week 16), and Visit 13 (Week 24). This outcome measure was reported for Visit 13.
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Time to Treatment Failure(TTF)
大体时间：From baseline until treatment failure assessed up to Visit 13 (Week 24)
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TTF measures the time from randomization to discontinuation of treatment for any reason, including, but not limited to, disease progression, treatment-related toxicity, and/or death during study.
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From baseline until treatment failure assessed up to Visit 13 (Week 24)
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Number of Serious Adverse Events (SAEs)
大体时间：From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
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This outcome measure calculates the total number of unique participants who reported serious adverse events (SAEs) in each group.
An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
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From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
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Incidence of Grade 3-4 Diarrhea
大体时间：From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
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This measure tracks the overall burden of severe (Grade 3) or life-threatening (Grade 4) diarrhea as defined by the NCI CTCAE v5.0.
Grade 3 events are severe enough to require medical intervention or significantly limit a person's ability to care for themselves, while Grade 4 events represent urgent, life-threatening clinical situations.
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From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
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Duration of Hospitalization
大体时间：From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
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This outcome measure calculates the sum of duration of hospitalizations during the study period in phase II population for both groups.
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From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
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Plasma Concentration of Natrunix
大体时间：Reported results Natrunix: Phase I: V1 post-dose collected at 30 min post-infusion at visit 1(Week 0), which represents Cmax of Cycle 1. Phase II: V6 pre-dose, at Visit 6 (Week 10), represents the trough of steady state concentration.
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Measurement of the concentration of Natrunix in plasma samples to evaluate the pharmacokinetic profile. Due to reporting limitations on this portal, results from only one time point are reported here. For Phase 1, samples were collected at V1 pre-dose, V1 post-dose, V2 pre-dose, V3 follow up. For phase 2, samples were collected at V1 pre-dose, V1 post-dose, V1 Day 4, V1 Day 7, V2 pre-dose, V3 pre-dose, V4 pre-dose, V6 pre-dose, V8 pre-dose, and V13 follow up. Placebo patients were tested at V1 post-dose only for verification. |
Reported results Natrunix: Phase I: V1 post-dose collected at 30 min post-infusion at visit 1(Week 0), which represents Cmax of Cycle 1. Phase II: V6 pre-dose, at Visit 6 (Week 10), represents the trough of steady state concentration.
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Number of Treatment Cycles
大体时间：From randomization to end of study or study discontinuation for any reasons, up to 24 weeks
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This measures the total number of cycles (total number of doses) received by subjects after randomization in each arm.
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From randomization to end of study or study discontinuation for any reasons, up to 24 weeks
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其他结果措施
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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症状问卷的结果将按治疗组在不同的输注后时间点进行总结，并随时间进行比较
大体时间：在长达 22 周的不同输注后时间点进行评估
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分数范围从 12 到 48。
高分代表较差的结果。
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在长达 22 周的不同输注后时间点进行评估
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通过按治疗组总结并随时间比较的所需 ECG 和心脏毒性相关事件的数量来测量心脏毒性
大体时间：随着时间的推移进行比较，评估长达 22 周
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探索性终点（仅限第 2 阶段部分）
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随着时间的推移进行比较，评估长达 22 周
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合作者和调查者
调查人员
- 学习椅：David J Park、Providence St. Joseph Heritage
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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