A Phase I, Open-Label, Multiple Ascending Dose Study to Assess the Safety and Tolerability of RRx-001 in Combination With Irinotecan in Metastatic or Advanced Cancer Patients Without Life-Prolonging Therapies of Demonstrated Clinical Benefit (PAYLOAD)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 28
- 试验地点
- 2
- 主要终点
- Number, frequency and type of adverse events
研究概览
简要总结
This is a phase 1 open-label trial to evaluate the safety, pharmacodynamics and clinical activity of RRx-001 administered in combination with irinotecan.
RRx-001 is associated with resensitization to irinotecan in tumors that are previously refractory. This effect has been attributed to the ability of RRx-001 to restore the expression of aberrantly silenced genes, thus re-establishing pathway functions. However, resensitization may have more than one mechanism, among them Pgp pump inhibition and vascular modulation, leading to improved penetration of standard chemotherapy.
详细描述
This dose escalation study consists of 5 sequential dose cohorts each administered RRx-001 with irinotecan. After the first 3 subjects of each cohort complete Cycle 1, the safety will be assessed before moving to the next dose level. Subjects in the current cohort will continue treatment immediately following the completion of Cycle 1, for as long as therapy is tolerated and the RECIST v.1.1 definition of progression is not met.
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
- •Histologically or cytologically confirmed diagnosis of an advanced, malignant, solid tumor(s) with all standard treatment options having been exhausted or declined.
- •Eastern Cooperative Group (ECOG) performance status is 0-2 at Screening.
- •Measurable disease per RECIST v1.1 by radiographic techniques
- •Acceptable liver function, serum creatinine and hematological status
- •Female subjects of childbearing potential, and male subjects with partners of childbearing potential, must agree to use medically acceptable methods of contraception beginning on Study Day 1 and continuing until at least four weeks after administration of the subject's final dose of RRx-
- •Subjects with brain metastases are eligible
排除标准
- •Concurrent anticancer therapy; however, radiotherapy is allowed
- •Any history of hypersensitivity to irinotecan
- •Cholangitis that required treatment or intervention within 4 weeks of study enrollment
- •Bilirubin > 2.0 mg/dL
- •Serious medical or psychiatric illness likely to interfere with participation in this clinical study
- •If female, subject is pregnant and/or breastfeeding.
- •UGT1A1*28 homozygote or heterozygote
研究组 & 干预措施
RRx-001 + Irinotecan
Cohorts of participants with an advanced, malignant, solid tumor(s) will receive weekly doses of RRx-001 for 3 weeks, switching at week 4 to every-other-week treatments of RRx-001 with irinotecan.
干预措施: RRx-001 (Drug)
RRx-001 + Irinotecan
Cohorts of participants with an advanced, malignant, solid tumor(s) will receive weekly doses of RRx-001 for 3 weeks, switching at week 4 to every-other-week treatments of RRx-001 with irinotecan.
干预措施: Irinotecan (Drug)
结局指标
主要结局
Number, frequency and type of adverse events
时间窗: 14 Weeks
次要结局
- Overall Survival(2 years)
- Overall Response rate(1 year)
- Duration of clinical benefit rate(1 year)
- Progression-Free Survival(1 year)