Effect and Safety of Apatinib on Radiation-Induced Brain Injury
关键词
抽象
描述
The incidence of nasopharyngeal carcinoma (NPC) is high in China especially in southern China. Radiotherapy is the mainstay of therapy for NPC and greatly improves patient survival. Along with promising therapeutic effects, complications such as radiation dermatitis, temporal lobe necrosis, cognitive impairment, and cranial nerve injury are also associated with radiotherapy. Previously, corticosteroids were considered conventional treatment for radiation-induced brain injury (RI). Unfortunately, only 20% patients with early phase RI seem to benefit from corticosteroid treatment. Moreover, the long-term use of steroids is associated with substantial adverse effects. Recently, bevacizumab, an anti-vascular endothelial growth factor (VEGF) recombinant monoclonal antibody, has been introduced as an efficient treatment for RI. However, the risk of severe adverse effects to bevacizumab, e.g. severe hypertension, proteinuria, nasopharyngeal necrosis and bleeding, limits its usage in certain patients with RI. Apatinib mesylate tablet is an oral small molecule tyrosine kinase inhibitor (TKI), which can specifically bind to vascular endothelial growth factor receptor 2 (VEGFR-2) and strongly inhibit neovascularization. Apatinib is currently used as a third-line treatment for advanced gastric cancer. Previous studies and clinical observation showed that apatinib could significantly improve brain injury after radiation, reduce brain tissue exudation and reduce edema. In this study, investigators will discuss the therapeutic effect of apatinib on RI and evaluate its safety through a prospective phase II clinical trial. It is hopeful to explore a new and effective method for the treatment of RI.
Primary objectives: The primary objective of this phase II, open-label, single-arm designed clinical trial is to evaluate the efficacy and safety of apatinib in patients with RI.
OUTLINE: This is a phase II, open-label, single-arm designed clinical trial. Participants are enrolled and administrated with oral apatinib mesylate tablet for 4 weeks.
Arm 1: Participants receive oral apatinib with a dosage of 250mg once daily for 4 weeks, in the absence of unacceptable toxicity or severe deterioration.
日期
| 最后验证: | 10/31/2019 |
| 首次提交: | 10/21/2019 |
| 提交的预估入学人数: | 11/02/2019 |
| 首次发布: | 11/04/2019 |
| 上次提交的更新: | 11/02/2019 |
| 最近更新发布: | 11/04/2019 |
| 实际学习开始日期: | 10/16/2019 |
| 预计主要完成日期: | 01/31/2020 |
| 预计完成日期: | 02/29/2020 |
状况或疾病
干预/治疗
Drug: Assigned Interventions
相
手臂组
| 臂 | 干预/治疗 |
|---|---|
| Experimental: Assigned Interventions Apatinib with a dosage of 250mg once daily for 4 weeks, in the absence of unacceptable toxicity or severe deterioration. | Drug: Assigned Interventions Apatinib with a dosage of 250mg once daily for 4 weeks, in the absence of unacceptable toxicity or severe deterioration. |
资格标准
| 有资格学习的年龄 | 35 Years 至 35 Years |
| 有资格学习的性别 | All |
| 接受健康志愿者 | 是 |
| 标准 | Inclusion Criteria: - Male or female patients aged ≥35 years; - Prior radiotherapy for histologically confirmed head and neck cancer ≥12 months prior to study entry; - Radiographic evidence to support the diagnosis of radiation-induced brain injury without tumor recurrence; - Estimated life expectancy must be greater than 12 months; - Routine laboratory studies：Bilirubin ≤ 1.0 × upper limits of normal (ULN)； Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 1.0 × ULN；Creatinine <1.0 × ULN；White-cell count ≥ 4,000 cells per cubic millimeter；Neutrophils count ≥1500 cells per cubic millimeter；Platelets ≥100,000 cells per cubic millimeter；Hemoglobin ≥110 gram per milliliter；Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR) within the normal ranges； - With sufficient cognitive function and language skills for communication and completion of study questionnaires; - Consent the enrollment of the study. Exclusion Criteria: - Evidence of tumor metastasis, recurrence, or invasion; - Current usage of bevacizumab; - Current usage of glucocorticoids; - Evidence of very high intracranial pressure that suggests brain hernia and the need for surgery; - History of psychiatric disease before radiotherapy; - History of seizures; - History of arteriosclerotic cardiovascular diseases (ASCVD), e.g. stroke, myocardial infarction, and unstable angina, within 6 months; - Present or previous history of cardiac arrhythmia; - New York Heart Association Grade II or greater congestive heart failure; - Significant vascular disease, e.g. moderate or severe carotid stenosis, aortic aneurysm, and history of aortic dissection; - Severe infection; - History of allergy to relevant drugs; - Pregnancy, lactation, or fertility program in the following 12 months; - History or current diagnosis of peripheral nerve disease; - Abnormal liver and renal function; - Active tuberculosis; - A previous history of organ transplantation; - Infection with the human immunodeficiency virus; - Participation in other experimental studies; - Subjects with any other condition which in the investigator's judgment might intervene the outcome of the study. |
结果
主要结果指标
1. Overall efficacy rate [4 weeks]
次要成果指标
1. Change of brain necrosis [4 weeks]
2. Change in neurological function [4 weeks]
3. Change in the quality of life [4 weeks]
4. Change of white matter structural connectivity [4 weeks]
5. Change in cognitive function [4 weeks]
6. Change in pain intensity [4 weeks]
