Phase I Study of Intratumor Injection of Anti-Mesothelin Immunotoxin LMB-100 With Ipilimumab in Malignant Mesothelioma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Number of Participants Who Experienced Grades 1-5 Serious and/or Non-serious Toxicity Related (= Possibly + Probably + Definitely) to LMB-100
研究概览
简要总结
Background:
Mesothelioma is a type of cancer. It originates in cells that line human body cavities. Most people have advanced disease when they are diagnosed. Researchers want to see if a combination of drugs can help.
Objective:
To find a safe dose of LMB-100 in combination with ipilimumab when LMB-100 is injected into tumors.
Eligibility:
Adults ages 18 and older with malignant pleural or peritoneal mesothelioma, that cannot be cured with surgery and has not responded to standard first-line treatments for mesothelioma.
Design:
Participants will be screened with:
- Tumor biopsy or effusion, if needed
- Medical history
- Physical exam
- Blood and urine tests
- Imaging scans
- Heart and lung function tests
- Pregnancy test, if needed
Some screening tests will be repeated during the study.
Participants will get LMB-100 on Days 1 and 4 for up to 2 cycles. Each cycle lasts 21 days. They will stay in the hospital for about 8 days each time they get LMB-100. It will be injected into their tumor with needles.
Participants will get ipilimumab through a tube that is put in a vein. It will be given on Day 2 of the first 2 cycles and Day 1 of the next 2 cycles.
Participants will be assessed for how well they do daily activities. They will give blood and tissue samples for research.
Participants will have a safety visit 4 to 6 weeks after the last dose of the study drugs. Then they will have scans every 6 weeks until their disease gets worse. If their tumor gets bigger, they will have phone, video, or email follow-ups every 12 weeks.
Participants will be on this study for life....
详细描述
Background:
LMB-100, and a closely related immunotoxin, SS1P, also targeting mesothelin, given intravenously, have been studied in Phase 1 clinical studies for mesothelioma and pancreatic cancer.
LMB-100 given intravenously results in systemic inflammation in patients, but as a single agent has limited anti-tumor efficacy.
Almost all patients develop neutralizing anti-LMB-100 antibodies after 2 cycles of therapy.
Intra-tumoral delivery of LMB-100 has been shown to induce immune cell infiltration in immune-competent mice, bearing murine malignant mesothelioma tumors. Combination with cytotoxic T-lymphocyte associated protein 4 (CTLA-4) blockage eradicates murine tumors by promoting anti-cancer immunity.
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 120 Years（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
1/Intra-tumoral LMB-100 Administration
Those with pleural or peritoneal mesothelioma receiving intra-tumoral administration of LMB-100 + ipilimumab for up to 4 cycles.
干预措施: Echocardiogram (Diagnostic Test)
1/Intra-tumoral LMB-100 Administration
Those with pleural or peritoneal mesothelioma receiving intra-tumoral administration of LMB-100 + ipilimumab for up to 4 cycles.
干预措施: LMB-100 (Biological)
1/Intra-tumoral LMB-100 Administration
Those with pleural or peritoneal mesothelioma receiving intra-tumoral administration of LMB-100 + ipilimumab for up to 4 cycles.
干预措施: ipilimumab (Drug)
1/Intra-tumoral LMB-100 Administration
Those with pleural or peritoneal mesothelioma receiving intra-tumoral administration of LMB-100 + ipilimumab for up to 4 cycles.
干预措施: Diphenhydramine (Drug)
1/Intra-tumoral LMB-100 Administration
Those with pleural or peritoneal mesothelioma receiving intra-tumoral administration of LMB-100 + ipilimumab for up to 4 cycles.
干预措施: Famotidine (Drug)
1/Intra-tumoral LMB-100 Administration
Those with pleural or peritoneal mesothelioma receiving intra-tumoral administration of LMB-100 + ipilimumab for up to 4 cycles.
干预措施: Acetaminophen (Drug)
1/Intra-tumoral LMB-100 Administration
Those with pleural or peritoneal mesothelioma receiving intra-tumoral administration of LMB-100 + ipilimumab for up to 4 cycles.
干预措施: Dexamethasone (Drug)
1/Intra-tumoral LMB-100 Administration
Those with pleural or peritoneal mesothelioma receiving intra-tumoral administration of LMB-100 + ipilimumab for up to 4 cycles.
干预措施: Biopsy (Procedure)
1/Intra-tumoral LMB-100 Administration
Those with pleural or peritoneal mesothelioma receiving intra-tumoral administration of LMB-100 + ipilimumab for up to 4 cycles.
干预措施: FDG-PET (Diagnostic Test)
1/Intra-tumoral LMB-100 Administration
Those with pleural or peritoneal mesothelioma receiving intra-tumoral administration of LMB-100 + ipilimumab for up to 4 cycles.
干预措施: CT CAP (Diagnostic Test)
1/Intra-tumoral LMB-100 Administration
Those with pleural or peritoneal mesothelioma receiving intra-tumoral administration of LMB-100 + ipilimumab for up to 4 cycles.
干预措施: MRI (Diagnostic Test)
1/Intra-tumoral LMB-100 Administration
Those with pleural or peritoneal mesothelioma receiving intra-tumoral administration of LMB-100 + ipilimumab for up to 4 cycles.
干预措施: ECG (Diagnostic Test)
结局指标
主要结局
Number of Participants Who Experienced Grades 1-5 Serious and/or Non-serious Toxicity Related (= Possibly + Probably + Definitely) to LMB-100
时间窗: Median follow-up: 3.4 months (1.9 months and 5.0 months)
Toxicity was assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. And Grade 5 is death related to adverse event.
Recommended Phase 2 Dose (RP2D) of Intratumorally Administered LMB-100 in Participants With Mesothelioma
时间窗: 21 days after first LMB-100 administration
RP2D is defined as the highest dose at which fewer than 2 of 6 participants experience a dose-limiting toxicity. A dose-limiting toxicity is defined as any Grade 4 hematological toxicity lasting greater than 5 days. Grade 3 febrile neutropenia, Grade 3 thrombocytopenia associated with bleeding episodes, any Grade 3 or greater, non-hematological toxicity with the following exceptions: tumor lysis syndrome, Grade 3 electrolyte changes associated with clinically significant consequences, Grade 3 nausea and diarrhea which has not received appropriate treatment, isolated Grade 3 fever occurring within 48 hours of LMB-100 infusion and resolving within 48 hours to ≤ Grade 2 and fully resolved within 1 week, alopecia, infusion-related reactions up to and including Grade 3, asymptomatic ≥ Grade 3 lymphopenia, leukopenia, hypoalbuminemia, electrolyte abnormalities resolving within 24 hours, and increase in alkaline phosphatase.
Number of Participants Who Experienced Grades 1-5 Serious and/or Non-serious Toxicity Related (= Possibly + Probably + Definitely) to Ipilimumab
时间窗: Median follow-up: 3.4 months (1.9 months and 5.0 months)
Toxicity was assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. And Grade 5 is death related to adverse event.
次要结局
- Duration of Response(Median follow-up: 3.4 months (1.9 months and 5.0 months))
- Progression Free Survival(Median: 1.4 months (95% CI: 0.6-2.3 months))
- Overall Survival(Median 3.4 months (1.9 months and 5.0 months).)
- Proportion of Participants Who Experienced an Objective Response Defined as Either a Partial or Complete Response(Median: 3.4 months (1.9 months and 5.0 months).)
研究者
Raffit Hassan, M.D.
Principal Investigator
National Cancer Institute (NCI)