Perioperative MVT-5873, a Fully Human Monoclonal Antibody Against a CA 19-9 Epitope, for Operable CA 19-9 Producing Pancreatic Cancers, Cholangiocarcinomas, and Metastatic Colorectal Cancers
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Number of Participants With Disease Recurrence At 1 Year
研究概览
简要总结
Background:
Gastrointestinal tumors have a molecule called carbohydrate antigen 19-9 (CA19-9) in the tumors and blood. The agent MVT-5873 was designed to block this molecule. Researchers want to test how safe it is to give this agent to people before and after surgery to remove a tumor. They want to learn the highest dose tolerated. They want to see if getting the agent at surgery helps slow down the disease.
Objective:
To test the safety of giving MVT-5873 at surgery to remove cancer and see if it slows the progression of the disease.
Eligibility:
Adults at least 18 years old with certain cancers and certain blood CA19-9 levels
Design:
Participants will be screened with:
- Medical history
- Physical exam
- Blood and heart tests
- Scans
- Review of normal activities
- Review of tumor sample
- Pregnancy test
A few days before surgery, participants will get a dose of the study agent. They will get it through a small plastic tube in a vein over about 2 hours.
Participants will sign a separate consent and have the surgery. A sample of the tumor and normal liver will be removed for research.
For 1-2 weeks after surgery, participants will recover in intensive care then regular care at the hospital. They will be monitored and treated throughout the stay.
After leaving the hospital, participants will get the study agent every week for 1 month. Then they will get it every other week for 2 months. They will repeat screening tests at study visits and at a follow-up visit. That will be about 5 weeks after the last dose.
详细描述
Background:
- Resections to remove tumors in the liver, bile ducts and pancreas are rarely curative, and patients frequently succumb to disease recurrence in the ensuing months to year(s) after the operation.
- Standard adjuvant therapies, which typically begin 6-12 weeks after surgery, offer little demonstrable decreases in the rates of tumor recurrence.
- The concept and implementation of immediate perioperative therapy has not been evaluated given the serious concerns related to healing and recovery with standard cytotoxic chemotherapy and newer targeted agents.
- A significant percentage of metastatic colorectal cancers, and primary tumors of the pancreas and bile ducts express Sialyl Lewis, an epitope on the well-established tumor marker, Carbohydrate antigen 19-9 (CA19-9).
- MVT-5873, a fully human antibody against Sialyl Lewis, has displayed antibody-dependent cell-mediated cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC) in vitro, potentiated chemotherapeutic efficacy in mouse models and demonstrated efficacy in Phase 1 trials of patients with advanced inoperable Hepato-pancreato-biliary (HPB) cancers.
- MVT-5873 is well tolerated as a single agent; moderate elevations in aspartate aminotransferase (AST)/alanine aminotransferase (ALT) appear to be dose-limiting.
- Patients with resectable Sialyl Lewis-expressing cancers represent an ideal population to explore the use of perioperative MVT-5873 given moderate level of CA 19-9 elevations, and the potential for extension of recurrence-free survival.
Objectives:
- Document the safety of perioperative MVT-5873 in patients undergoing pancreas and liver resections.
- Determine if perioperative MVT-5873 can decrease 1-year recurrence rates for patients with operable CA 19-9-producing cancers.
Eligibility:
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
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Cohort 1 - Pre-operative Escalation Doses of MVT-5873 (HuMab-5B1)
Pre-operative escalation doses of MVT-5873, pancreatectomy or hepatectomy and post-operative MVT-5873 treatment
干预措施: MVT-5873 (Drug)
Cohort 1 - Pre-operative Escalation Doses of MVT-5873 (HuMab-5B1)
Pre-operative escalation doses of MVT-5873, pancreatectomy or hepatectomy and post-operative MVT-5873 treatment
干预措施: pancreatectomy or hepatectomy (Procedure)
Cohort 2 - Pre-operative Recommended Dose (RD) of MVT-5873 (HuMab-5B1)
Pre-operative RD of MVT-5873, pancreatectomy or hepatectomy and post-operative MVT-5873 treatment
干预措施: MVT-5873 (Drug)
Cohort 2 - Pre-operative Recommended Dose (RD) of MVT-5873 (HuMab-5B1)
Pre-operative RD of MVT-5873, pancreatectomy or hepatectomy and post-operative MVT-5873 treatment
干预措施: pancreatectomy or hepatectomy (Procedure)
结局指标
主要结局
Number of Participants With Disease Recurrence At 1 Year
时间窗: 1 year
Disease recurrence is defined as new disease measurable on computed tomography (CT)/magnetic resonance imaging (MRI) that was not present on the baseline CT/MRI.
Number of Grade 3-5 Adverse Events Related and/or Not Related to Drug
时间窗: Date treatment consent signed to date off study, approximately 29 months and 11 days, and 22 months and 21 days for cohort 1 and cohort 2 respectively.
Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse events.
次要结局
- Define Disease Free Survival (DFS) for Participants Treated With Preoperative MVT-5873(An average of 15.17 months)
研究者
Jonathan Hernandez, M.D.
Investigator
National Cancer Institute (NCI)