Targeted Therapy in Children and Adolescents With Recurrent, Progressive and Unresectable Inflammatory Myofibroblastic Tumor With the Inhibitor of Tyrosine Kinase -Crizotinib
试验速览
- 阶段
- 2 期
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Overall response rate
研究概览
简要总结
Targeted therapy based on target identification by genetic examinations is a promising direction in the treatment of patients with a complicated course of inflammatory myofibroblastic tumor. Recently, the main work covered in foreign publications, aimed at finding additional methods of treatment, by identifying new targets for targeted therapy in patients with unresectable IMT, but currently there is no standardized approach to the treatment of IMT in children worldwide.
This study can show the benefits of the usage of crizotinib as targeted therapy in children with ALK/ROS1 positive unresectable, progressive or reccurent inflammatory myofibroblastic tumors. The main hypothesis is that crizotinib would increase an objective response rate in this group of patients.
详细描述
Inflammatory myofibroblastic tumor (IMT) is a rare type of childhood neoplasm characterized by intermediate biological behavior. The main method of treatment of this tumor is a complete surgical removal. It should be said, that in 2-5% of patients the presence of distant metastases was noted at the time of diagnosis, in addition, the complex anatomical localization of the process sometimes does not allow a radical surgical intervention. In patients with unresectable IMT, the presence of distant metastases, residual tumor after initial resection or progression of the disease, attempts have been made to prescribe therapy with steroids , nonsteroidal anti-inflammatory drugs (NSAIDs), cytostatic drugs. However, the effectiveness of this therapy was low.
Since the late 90s, it is known that with the identification of a number of specific cytogenetic changes, this type of neoplasm is a true neoplastic process. In 50% of all cases of IMT there are clonal translocations of the ALK gene located at the 2p23 encoding the anaplastic lymphoma kinase (ALK). It was shown that ALK gene activation is based on translocations involving a large number of partner genes with tyrosine kinase activity. Currently, there are more than 21 partner genes involved in the formation of chimeric transcripts. The most frequent are TPM3, TPM4, CLTC, CARS, RANBP, EML4, TFG.
The introduction of modern molecular genetic methods, including the next generation sequencing (NGS), has expanded the understanding of the mechanisms of carcinogenesis in IMT. Along with ALK gene rearrangements, the ROS1 gene (YWHAE-ROS1 and TFG-ROS1) and PDGFRB (NAB2) genes were detected in the group of patients with ALK-negative IMT.
The therapy with tyrosine kinase inhibitors (crizotinib) has become possible not only in patients with ALK-positive tumor, but also in a group of patients who do not have an ALK gene rearrangement, but in whom a rearrangement of the ROS1 gene has been detected [4].
Previously, large-scale studies using tyrosine kinase inhibitors (crizotinib) have not been conducted in patients under 18 with IMT.
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
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 0 - 18 years
- •The presence of a histologically verified diagnosis of Inflammatoru Myofibroblastic Tumor, confirmed in the pathology laboratory of Dmitry Rogachev National Research Center
- •The presence of ttumor masses according to CT or MRI at the time of inclusion in the protocol
- •Unresectable or metastatic tumor
- •Relapse or progressive disease
- •Good perfomance status
- •Normal function of bone marrow
- •Normal function of a liver
- •Normal levels of creatinine and urea in blood
- •Nornal heart funсtion (LVEF > 60%)
- •Clear expression of rearranged ALK/ROS1 genes
- •Signed Informed Consent
排除标准
- •Age >18 years
- •Refusal of signing the form of the informed consent
- •The presence of comorbidities, which may endanger patient safety
- •No rearrangements of ALK/ROS genes
- •No signs of existing tumor, according to CT and MRI
研究组 & 干预措施
crizotinib +
Patients with unresectable, relapsed or refractory inflammatory myofibroblastic tumor, receiving crizotinib
干预措施: Crizotinib (Drug)
结局指标
主要结局
Overall response rate
时间窗: 2 months
The frequency of response to therapy with Crizotinib in patients with translocation of the ALK / ROS1 genes and their partners.
次要结局
- Relapse-free survival(5 years)
- Overall survival(5 years)