Phase 1/2a Study of DTA-H19 in Advanced Stage Ovarian Cancer
Phase 1/2a, Dose-Escalation, Safety, Pharmacokinetic, and Preliminary Efficacy Study of Intraperitoneal Administration of DTA-H19 in Subjects With Advanced Stage Ovarian Cancer
研究概览
详细说明
This is a Phase 1/2a, open label, dose escalation, repeat dose study in 11 subjects with recurrent, platinum resistant advanced stage ovarian cancer or primary peritoneal carcinoma designed to determine the tolerability, safety, quality of life, PK, and preliminary efficacy of DTA-H19 administered intraperitoneally(IP).
Primary Objective: The primary objectives of this study are:
- To determine the maximum tolerated dose (MTD) of IP DTA-H19; and,
- To identify any dose limiting toxicities (DLTs).
Secondary Objectives: Secondary objectives of this study are:
- To determine quality of life of subjects with advanced ovarian cancer, primary peritoneal carcinoma treated with IP DTA-H19;
- To determine the the reduction in malignant ascites as measured by Ultrasound and change in frequency of parecenteses necessary.
- To determine the overall survival distribution.
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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Holon、以色列
- The Edith Wolfson Medical Center
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Jerusalem、以色列
- Hadassah University Hospital
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Kfar Saba、以色列
- Meir Hospital
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Tel Hashomer、以色列
- Sheba medical 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
有资格学习的性别
描述
Inclusion Criteria:
- Provide written informed consent and be at least 18 years of age.
- Have histopathologically documented epithelial ovarian carcinoma or primary peritoneal carcinoma with evidence of ascites.
- Have either a) platinum-refractory disease (i.e. persistent disease following completion of platinum-based primary chemotherapy) and have failed at least primary platinum-based chemotherapy; or b) platinum-resistant recurrent disease and have failed at least one regimen of second line chemotherapy.
- Be able to tolerate placement of IP catheter.
- Be at least 2 weeks from last treatment to allow recovery from prior toxicity but in the judgment of the investigator with sufficient time to ensure that the effects of prior treatments will not confound safety evaluations.
- Have a Karnofsky performance status score of ≥ 70%.
- Not be of child-bearing potential.
- Have a life expectancy of ≥ 3 months.
- Have serum creatinine < 2.0 mg/dL, total bilirubin less than the institution's 3x upper limit of normal (ULN); AST and ALT <= 2.5 x ULN,total albumin ≥ 2.5 g/dL, PT, PTT, and PT/INR within normal limits, absolute neutrophil count (ANC) > 1,500 x 103 cells/mL, platelets ≥ 100,000/mL, and hemoglobin ≥ 10 mg/dL.
- Have a biopsy specimen or an ascites fluid that is positive for H19 expression.
- Have screening procedures completed within 6-weeks before starting treatment.
- No significant history of cardiac disease, i.e., uncontrolled hypertension, unstable angina or congestive heart failure.
- - No plans to receive concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy or any other type of therapy for treatment of cancer while on this protocol.
Exclusion Criteria:
- Have evidence of extra abdominal disease with the exception of isolated small nodules (e.g., liver or pulmonary nodules) that are not causing symptoms.
- Have known brain metastases.
- Have known HIV infection.
- Have known active viral or bacterial infections.
- Have presence of any psychological, familiar, sociological, or geographical condition potentially hampering compliance with the study protocol or follow up schedule.
- Have a medical condition contraindicated for laparotomy, laparoscopy, or surgery.
- Have significant bowel involvement denoted by persistent grade 3 vomiting (≥6 episodes in 24 hrs; IV fluids, or total parenteral nutrition (TPN) indicated ≥24 hrs) after removal of ascites, inability to tolerate oral diet or medications, requirement for total parenteral nutrition, or recent (past six weeks) episode of bowel obstruction.
- Have a history of coagulopathy.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的:BC-819
BC-819 60, 120 and 240 mg IP administration
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Cohort #1: 60 mg IP weekly for 3 weeks, one week rest, then repeat for 2 more courses / 60 mg IP weekly for 3 weeks, four week rest, then repeat for 1 more course. Cohort #2: 120 mg IP weekly for 3 weeks, four week rest, then repeat for 1 more course. Cohort #3: 240 mg IP weekly for 3 weeks, four week rest, then repeat for 1 more course.
其他名称:
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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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Number of Participants With Dose-Limiting Toxicities
大体时间:8 weeks
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A dose limiting toxicity (DLT) was defined as any grade 3 or greater non-hematologic AE by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE).
If one subject in a cohort experienced a DLT, then three additional subjects had to be enrolled to that cohort unless a second subject in that cohort experiences a DLT.
The next lower dose was to be considered the MTD.
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8 weeks
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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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Overall Survival in ITT Population
大体时间:17.5 months
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Overall survival, defined as the time from the start of treatment until the subject died, was estimated by Kaplan Meier curves.
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17.5 months
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Solid Tumor Response
大体时间:6 weeks
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If measurable disease was present, then the response of each marker lesion was evaluated separately and rated for response according to RECIST criteria for solid tumors. Complete Response: Disappearance of the target lesion. Partial Response: At least a 30% decrease in the longest diameter of the target lesion. Stable Disease: No sufficient shrinkage to qualify for partial response, or sufficient increase to qualify for progressive disease. Progressive Disease: At least a 20% increase in the longest diameter of the target lesion. |
6 weeks
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Systemic BC-819 Pharmacokinetics (PK) by Treatment - T1/2 (Hours)
大体时间:Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion
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Blood was collected at the indicated time points, then analyzed with a quantitative polymerase chain reaction (Q-PCR) method to quantitate the amount of plasmid present.
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Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion
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Systemic BC-819 Pharmacokinetics (PK) - Maximum Observed Plasma Concentration (Cmax)
大体时间:Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion
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Blood was collected at the indicated time points, then analyzed with a quantitative polymerase chain reaction (Q-PCR) method to quantitate the amount of plasmid present.
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Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion
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Systemic BC-819 Pharmacokinetics (PK) by Treatment - Tmax (Hours)
大体时间:Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion
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Blood was collected at the indicated time points, then analyzed with a quantitative polymerase chain reaction (Q-PCR) method to quantitate the amount of plasmid present.
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Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion
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Systemic BC-819 Pharmacokinetics (PK) by Treatment - AUClast
大体时间:Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion
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Blood was collected at the indicated time points, then analyzed with a quantitative polymerase chain reaction (Q-PCR) method to quantitate the amount of plasmid present.
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Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion
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Systemic BC-819 Pharmacokinetics (PK) by Treatment - AUCinf
大体时间:Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion
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Blood was collected at the indicated time points, then analyzed with a quantitative polymerase chain reaction (Q-PCR) method to quantitate the amount of plasmid present.
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Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion
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Overall Survival in PP
大体时间:17.5 months
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Overall survival, defined as the time from the start of treatment until the subject died, was estimated by Kaplan Meier curves.
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17.5 months
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合作者和调查者
调查人员
- 首席研究员:Tally Levy, M.D.、The Edith Wolfson Medical Center
- 首席研究员:David Edelman, MD、Hadassah University Hospital
- 首席研究员:Ami Fishman, MD、Meir Medical Center
- 首席研究员:Eitan Rami, MD.、Rabin Medical Center
- 首席研究员:Ofer Lavie, M.D.、Carmel Medical Center
- 首席研究员:Ronnie Shapira-Frommer, MD、Sheba medical center
研究记录日期
研究主要日期
学习开始
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 (估计)
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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