An Investigator Sponsored Phase 1a/1b Trial of Selinexor in Combination With Irinotecan in Patients With Adenocarcinoma of Stomach and Distal Esophagus
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
The main purpose of this study is to see whether the combination of selinexor (KPT-330) and irinotecan can help people with esophageal or stomach cancer. Researchers also want to find out if the combination of selinexor (KPT-330) and irinotecan is safe and tolerable.
详细描述
This is an open label, single group, non-randomized, phase I study with cohort expansion that utilizes the standard 3+3 design for dose. The dose of selinexor will be escalated in combination with the standard doses of irinotecan. The maximum tolerated dose (MTD) for study is defined as the highest dose level at which 1 or less of 6 patients experience a dose limiting toxicity DLT.
Once the MTD is reached and/or the recommended dose for expansion is determined, an additional cohort of 15 patients with advanced gastric or esophageal cancer will be accrued to better define the safety and tolerability of the combination regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Must have histologically confirmed gastric, gastro-esophageal junction or distal esophageal adenocarcinoma (predominant histology) that is recurrent, metastatic or unresectable
- •Must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1
- •Must have received at least one line but less than three lines of prior systemic therapies and have either progressed or intolerant to prior therapies. Patients who have received adjuvant/neoadjuvant therapy within last one year will be eligible as well.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- •Life expectancy of greater than 3 months
- •Must have normal organ and marrow function
- •Women of child-bearing potential (WOCBP) must agree to use dual methods of contraception and have a negative serum pregnancy test at screening. Male participants must use an effective barrier method of contraception if sexually active with a WOCBP. For both male and female participants, effective methods of contraception must be used throughout the study and for three months following the last dose.
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Have had chemotherapy, biologic therapy or radiotherapy within 3 weeks prior to entering the study
- •Are receiving any other investigational agents for anti-cancer treatment within 3 weeks of starting study medication
- •Symptomatic central nervous system (CNS) metastases
- •Progression on irinotecan containing regimen
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to irinotecan
- •Major surgery within 2 weeks before cycle 1 Day 1 (C1D1)
- •Unstable cardiovascular function
- •Patients who are pregnant or lactating
- •Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; patients with controlled infection or on prophylactic antibiotics are permitted in the study.
- •Known active hepatitis A, B, or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen)
- •Any underlying condition that would significantly interfere with the absorption of an oral medication
- •> Grade 2 peripheral neuropathy at baseline
- •Serious psychiatric or medical conditions that could interfere with treatment
- •Concurrent therapy with approved or investigational anticancer therapeutic other than steroids
- •History of gastrointestinal perforation and/or fistulae within 6 months prior to C1D1
- •Use of strong CYP3A4 inducers or inhibitors within 2 weeks of starting study medication
研究组 & 干预措施
Selinexor in Combination with Irinotecan
The first study drug is called selinexor (KPT-330). This drug is taken by mouth on days 1, 3, 8 and 10 of each cycle. The starting dose of selinexor will be dependent on the cohort in which the patient is enrolled into. Level -1: 25 mg/m^2; Level 1: 40 mg/m^2; Level 2: 50 mg/m^2; Level 3: 65 mg/m^2.
The second drug is called irinotecan. This drug is given as intravenous (IV) infusion on days 1 and 8 of each cycle. Participants will receive the standard recommended dose: 125 mg/m^2.
干预措施: Selinexor (Drug)
Selinexor in Combination with Irinotecan
The first study drug is called selinexor (KPT-330). This drug is taken by mouth on days 1, 3, 8 and 10 of each cycle. The starting dose of selinexor will be dependent on the cohort in which the patient is enrolled into. Level -1: 25 mg/m^2; Level 1: 40 mg/m^2; Level 2: 50 mg/m^2; Level 3: 65 mg/m^2.
The second drug is called irinotecan. This drug is given as intravenous (IV) infusion on days 1 and 8 of each cycle. Participants will receive the standard recommended dose: 125 mg/m^2.
干预措施: Irinotecan (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: Up to 18 months
The MTD for study is defined as the highest dose level at which 1 or less of 6 patients experience a dose limiting toxicity (DLT).
次要结局
- Progression Free Survival (PFS)(Up to 18 months)
- Objective Response Rate (ORR)(Up to 18 months)
- Best Overall Response(Up to 18 months)
- Overall Survival (OS)(Up to 18 months)