Protocol for Treatment Under Hospital Exemption: T Cell Receptor Based Therapy of Metastatic Colorectal Cancer With mRNA-engineered T Cells Targeting Transforming Growth Factor Beta Receptor Type II (TGFβII)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Incidence, nature, and severity of adverse events graded according to NCI CTCAE v4.0
研究概览
简要总结
T Cell Receptor Based Therapy of Metastatic Colorectal Cancer With mRNA-engineered T Cells Targeting Transforming Growth Factor Beta Receptor Type II (TGFβII)
详细描述
Patients with advanced metastatic colorectal cancer who have no other effective treatment options will be offered the treatment. These patients have a poor prognosis, and there is a strong need for improved therapy.
The patients will be given adoptive cell therapy (ACT) with Radium-1 TCR+ T cells transiently redirected against the TGFβRII frameshift antigen which is expressed in MSI+ colon cancer. The first report on TCR therapy in colon cancer was targeting carcinoembryonic antigen (CEA) where some evidence of clinical response was seen, but the T-cell function may have been inhibited due to the necessity to resolve the severe colitis which occurred due to the presence of CEA in normal cells in the colon. This demonstrates the feasibility of T-cell therapy in metastatic colon cancer, but also the limitations of targeting CEA as an antigen.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with metastatic colon cancer which is MSI+ with the presence of the -1A deletion in TGFβRII gene, and positive for HLA-A02 genotype
- •Measurable disease
- •Female or male patients. Fertile females must have a negative pregnancy test before inclusion in the trial. Both fertile men and women must be ready and able to use highly effective methods of contraception, defined as use of oral, implanted, injectable, and mechanical or barrier products for the prevention of pregnancy during participation of the trial
- •Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1
- •Age 18 years and older
- •Life expectancy of at least 3 months
- •Signed informed consent (by the subject or subject's legal representative) obtained before any trial-related procedures.
- •Adequate organ function, measured by pre-defined laboratory values
排除标准
- •Other metastatic malignancies
- •Any other anti-tumour treatment within 4 weeks prior to first administration of cells.
- •Steroid treatment, except substitution dose
- •Significant cardiac or other medical illness that would limit activity or survival, such as severe congestive heart failure, unstable angina or serious cardiac arrhythmia
- •Active infection requiring antibiotic therapy
- •Pregnancy or lactation
- •Known hypersensitivity to any of the components of the investigational product
- •Patients who test positive for hepatitis B, C, HIV or syphilis
- •Any reason why, in the opinion of the investigator, the patient should not participate
研究组 & 干预措施
Adoptive Cell Therapy (ACT)
The ACT will be administered as two intravenous (i.v.) injections of GMP TCR T cells per week for 6 weeks.
Escalating dose per week, from 1 x108 cells (week 1) to 2x109 cells (week 4 onwards) using a central venous catheter. The doses listed indicate the maximum number of T cells per injection at any given time point.
干预措施: Adoptive Cell Therapy (ACT) (Biological)
结局指标
主要结局
Incidence, nature, and severity of adverse events graded according to NCI CTCAE v4.0
时间窗: 2 years
Incidence, nature, and severity of adverse events graded according to NCI CTCAE v4.0
次要结局
- Overall survival (OS)(2 years)
- Progression free survival (PFS)(2 years)
- Radiological response rate (ORR)(2 years)
研究者
Svein Dueland
Principal Investigator
Oslo University Hospital