A Pilot Study of AMP-224, a PD-1 Inhibitor, in Combination With Stereotactic Body Radiation Therapy (SBRT) in Patients With Metastatic Colorectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)
研究概览
简要总结
Background:
- T-cells are white blood cells that can find and kill germs and tumors. Cancer can keep T-cells from working. Researchers think a new drug called AMP-224 might help the T-cells in people with cancer. They think the drug might work even better when combined with a certain type of radiation therapy.
Objective:
- To study the safety and effectiveness of AMP-224 together with 1 or 3 days of stereotactic body radiation therapy (SBRT) directed to the liver.
Eligibility:
- People age 18 and older with metastatic colorectal cancer. Their cancer must have spread to the liver and not be responding to treatment.
Design:
- Participants will be screened with a medical history, physical exam, and blood and urine tests. Their tumors will be measured with computerized tomography (CT) scans or magnetic resonance imaging (MRI) of the chest, stomach, and pelvis. They will have an electrocardiogram (ECG) heart test.
- Participants will have a small part of their tumor removed by needle (biopsy).
- Participants will have 8 study visits over about 10 weeks.
- At 1 visit, they will have another tumor biopsy.
- At 1 visit, they will get a chemotherapy drug through a vein (intravenous (IV)).
- At 6 visits, they will receive AMP-224 through an IV.
- At 1 or 3 visits, they will have SBRT. Computed tomography (CT) scans will map the position of their tumor. Radiation beams of different intensities at different angles will be directed to the tumor.
- At all visits, some screening procedures may be repeated.
- After treatment ends, participants will have 7 follow-up visits over about 5 months. Blood will be drawn. Some screening procedures may be repeated.
详细描述
Background:
- Colorectal cancer remains the second leading cause of cancer death in western countries with a median survival of approximately 24 months despite recent advances in systemic treatment.
- Several preclinical studies have documented an increase in peripheral antitumor immunity following radiation, a phenomenon known as the abscopal effect. Tumor PDL1 expression has also been shown to be induced by radiation, which can suppress the anti-tumor immune response. Inhibition of programmed cell death-1 (PD-1)/programmed death ligand-1(PDL-1) axis has been shown to improve anti-tumor immunity by blocking the tumor-mediated suppression of cytotoxic T cells.
- AMP-224, a B7-DC Fc fusion protein, binds to PD-1, an inhibitory receptor that is present on the cell surface of exhausted, activated, effector, and memory T cells. AMP- 224 has a unique mechanism of action in that it binds specifically to PD-1HI T cells (chronically stimulated / exhausted T cells) but not to PD-1LO cells which represent the normal activated T cells population
- The aim of the study is to evaluate whether the anti-tumor immunity of anti-PD1 therapy (with AMP-224) can be enhanced by radiation therapy.
Objectives:
- To assess safety, tolerability and feasibility of AMP-224 in combination with stereotactic body radiation therapy (SBRT) in patients with metastatic colorectal cancer.
Eligibility:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 99 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
DL1 - CTX, SBRTx1 day, & AMP-224
Dose Level 1 (DL1) Cyclophosphamide (CTX) 200mg/m(2) intravenous (IV) on day 0. Stereotactic body radiation therapy (SBRT) 8 (gray)Gy x 1 day on day 0, AMP-224 10mg/kg on day 1 then every (q)14 days for a total of 6 doses
干预措施: AMP-224 (Drug)
DL1 - CTX, SBRTx1 day, & AMP-224
Dose Level 1 (DL1) Cyclophosphamide (CTX) 200mg/m(2) intravenous (IV) on day 0. Stereotactic body radiation therapy (SBRT) 8 (gray)Gy x 1 day on day 0, AMP-224 10mg/kg on day 1 then every (q)14 days for a total of 6 doses
干预措施: Stereotactic Body Radiation Therapy(SBRT) (Radiation)
DL1 - CTX, SBRTx1 day, & AMP-224
Dose Level 1 (DL1) Cyclophosphamide (CTX) 200mg/m(2) intravenous (IV) on day 0. Stereotactic body radiation therapy (SBRT) 8 (gray)Gy x 1 day on day 0, AMP-224 10mg/kg on day 1 then every (q)14 days for a total of 6 doses
干预措施: Cyclophosphamide (Drug)
DL2 - CTX, SBRTx3 days, and AMP-224
Dose Level 2 (DL2) CTX 200mg/m(2) IV on day 0, SBRT 8Gy x 3 day on days -2, -1, and 0. AMP-224 10mg/kg on day 1 then q14 days.
干预措施: AMP-224 (Drug)
DL2 - CTX, SBRTx3 days, and AMP-224
Dose Level 2 (DL2) CTX 200mg/m(2) IV on day 0, SBRT 8Gy x 3 day on days -2, -1, and 0. AMP-224 10mg/kg on day 1 then q14 days.
干预措施: Stereotactic Body Radiation Therapy(SBRT) (Radiation)
DL2 - CTX, SBRTx3 days, and AMP-224
Dose Level 2 (DL2) CTX 200mg/m(2) IV on day 0, SBRT 8Gy x 3 day on days -2, -1, and 0. AMP-224 10mg/kg on day 1 then q14 days.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)
时间窗: Date treatment consent signed to date off study, approximately 24 months and 8 days
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
次要结局
- Duration of Response in Patients With Colorectal Cancer During and Following Treatment With AMP-224 in Combination With SBRT(12 months)
- Number of Participants in Which Specimens Were Collected for Pre and Post Pharmacokinetic (PK) AMP-224 Analyses(Baseline and post infusion AMP-224 (e.g. 15 minutes after infusion ended))
- Overall Survival in Patients With Colorectal Cancer Following Treatment With AMP-224 in Combination With SBRT(Baseline to end of study, which is date of death. Average time participants were followed was 10.6 months.)
- Count of Participants With Post-Treatment Biopsies(Post treatment, day 29 +/- 7 days)
- Median Progression-free Survival in Patients With Colorectal Cancer(Baseline to disease progression, an average of 2.6 months.)
- Immunogenicity of AMP-224 as Measured by Human Anti-Murine Antibodies (HAMA) and Human Anti-Chimeric Antibodies (HACA) Concentrations(Baseline, D1, D29, and D57 (pre-infusion), D79, D85 and 90 days post last dose (D169))
- Area of the Curve (AUC) of AMP-224(Pre and post-infusion with all the AMP infusion and Day 1 at 8, 15, 29, 43, 57, and 71 hours.)
- Objective Response Rate(Restaging was done every 8 weeks for an average of 2.6 months.)
- Terminal Elimination Half-Life of AMP-224(10 days)
- Time to Maximum Observed Plasma Concentration (Tmax) of AMP-224(12.7 hours following intravenous (IV) infusion.)
研究者
Tim Greten, M.D.
Principal Investigator
National Cancer Institute (NCI)