An Open-label Phase 1 Trial of the Safety and Efficacy of Daily Subcutaneous SPL-108 Injections When Used In Combination With Paclitaxel In Patients With Platinum-resistant, CD44+, Advanced Ovarian Epithelial Cancer
试验速览
- 阶段
- 1 期
- 入组人数
- 14
- 试验地点
- 2
- 主要终点
- Incidence of Adverse Events (Safety)
研究概览
简要总结
Up to 18 women with ovarian cancer will administer up to two injections of SPL-108 daily in combination with weekly doses of Paclitaxel. They will be monitored for safety and efficacy for up to 6 months, until disease progression or unacceptable toxicity.
详细描述
This is an open-label 2-arm trial. Eligible subjects will be screened and enrolled sequentially into 1 of 2 Arms:
Arm I: N=6 to 12 subjects, Safety Phase
- Cohort 1 SPL-108 x 1 injection daily + 80 mg/m2 PTX weekly on Days 1, 8, and 15 in 28 day cycles
- Cohort 2 SPL-108 BID + 80 mg/m2 PTX weekly on Days 1, 8, and 15 in 28 day cycles
For Arm I, at least 1 week will elapse between Dose 1 for each subject.
In Cohort 1, 3 subjects will be enrolled: if 1 dose-limiting toxicity (DLT) occurs, 3 subjects will be added at this dose level; if 0/3 or 1/6 DLTs occur, Cohort 2 will initiate enrolling subjects; if 2 or more DLTs occur at this dose level, subjects will not be enrolled in Cohort 2 and the trial will be terminated.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Females ≥18 years of age
- •Platinum-resistant recurrent or metastatic epithelial ovarian carcinoma
- •Positivity on CD44 assay as defined by strong (+++) or moderate (++) staining in 20% or more of the tumor tissue/stroma as obtained by biopsy or paracentesis
- •Status post first-line therapy with definitive surgery (which provided tissue for pathologic diagnosis) and chemotherapy
- •Original diagnosis has been confirmed through a histopathologic review of the primary tumor slides by an expert pathologist at the Principal Investigator's institution
- •Disease has progressed or recurred during or less than 6 months after platinum-based chemotherapy at some point during the subject's course.
- •No more than 3 prior regimens of cytotoxic chemotherapy unless approved by the sponsor (Note: all platinum-containing regimens are not to be counted separately but are considered to be a single regimen for the purposes of this criterion)
- •Measurable disease by RECIST 1.1 criteria
- •Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, 1, or 2
- •Women with childbearing potential and partners must both use effective contraception during the study and for 3 months after the last dose
- •Life expectancy of at least 6 months
- •Able to understand and comply with the study procedures, understand the risks involved in the study, and provide written informed consent before the first study-specific procedure
排除标准
- •Treatment with cytotoxic chemotherapy for malignancies other than ovarian cancer within the past 5 years
- •Fewer than 28 days before Cycle 1 Day 1 since any prior chemotherapy (less than 42 days in the case of mitomycin or a nitrosourea)
- •Fewer than 28 days before Cycle 1 Day 1 since administration of hormonal or biological anti-neoplastic agents
- •Concomitant use of other cytotoxic or cytostatic drugs other than PTX
- •Abnormal clinical laboratory values within 14 days prior to initiation of dosing, as indicated by:
- •Hemoglobin level <9.0 gm/L
- •Platelet count <100,000/mm3
- •Granulocyte count <1500/mm3
- •Serum creatinine level ≥2.5 mg/dL (221 μmol/L)
- •Liver aminotransferase levels greater than 3 times the laboratory's upper limit of normal (greater than 5 times the laboratory's upper limit of normal if the liver is known to be involved with tumor)
- •Contraindication to the use of PTX
- •Pregnancy or breast-feeding at time of Screening and throughout the study.
- •Active, uncontrolled infection
- •Participation in another investigational drug trial concurrently or within 30 days of Cycle 1 Day 1, or a vaccine trial within 90 days of Cycle 1 Day 1
- •Significant acute or chronic medical or psychiatric illness that, in the judgment of the Investigator, could compromise subject safety, limit the subject's ability to complete the trial, and/or compromise the objectives of the trial
研究组 & 干预措施
Safety Phase
Six to 12 subjects
- Cohort 1 SPL-108 injection daily + 80 mg/m2 PTX weekly on Days 1, 8, and 15 in 28 day cycles
- Cohort 2 SPL-108 BID injection + 80 mg/m2 PTX weekly on Days 1, 8, and 15 in 28 day cycles
干预措施: SPL-108 (Drug)
Exploratory Expansion Phase
Up to 12 subjects
• Cohort 3: SPL-108 daily dose (to be determined in Arm I) + 80 mg/m2 PTX weekly on Days 1, 8, and 15 in 28 day cycles.
干预措施: SPL-108 (Drug)
结局指标
主要结局
Incidence of Adverse Events (Safety)
时间窗: Until dose-limiting toxicity, disease progression or 6 months
Includes adverse events, laboratory data, physical examination findings, vital signs, weight and ECOG Performance Status
次要结局
- Response to Investigational Product(Until dose-limiting toxicity, disease progression or 6 months)