High-dose Topotecan for Retinoblastoma With Recurrent or Refractory Vitreous Seed(A Prospective Non-controlled Single Arm Trial)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Tumor response
研究概览
简要总结
Retinoblastoma is the most common intraocular malignancy in infancy and childhood,with an estimated 8000 new cases globally each year.The major cause of failure in the management of retinoblastoma remains the persistence or recurrence of resistant vitreous seeding.Currently,with the emergence of new administration routes, intravitreal chemotherapy has been used for vitreous seeds and the rate of eye preservation has been effectively improved. However, the use of high doses of chemotherapeutic agents may lead to visual impairments due to long term retinal toxicity and some tumors recur or become resistant to chemotherapeutic agents after treatment. In such cases, ocular resection is the only option to prevent extraocular metastasis and death.
Therefore, studies on retinoblastoma are currently focused on finding new targeted therapies at appropriate doses to increase anti-tumor activity and reduce side effects. In this study, Topotecan at a dosage of 100μg will be used to treat patients with refractory or recurrent retinoblastoma.
On one hand, topotecan, as a topoisomerase I inhibitor, prevents the reconnection of broken single stranded DNA, causing irreversible DNA damage. On the other hand, topotecan upregulates PTEN protein to restore its inhibitory effect on the PI3K/AKT signaling pathway, thereby jointly promoting tumor cell apoptosis and weakening cell proliferation activity.Topotecan at a dosage of 100μg has been proven safe in animal experiments, and there have been a few retrospective case reports on its application in retinoblastoma, but relevant prospective clinical studies are still lacking.
Based on the above background, this study will explore the feasibility and effectiveness of intravitreal injection of Topotecan at a dosage of 100μg in patients with refractory or recurrent retinoblastoma through a prospective study,while evaluating immune response and visual preservation.
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
- 1 Year 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with retinoblastoma with a somatic mutation of the gene RB1 and active tumor in a single eye, or germinal mutation of RB1 with active tumor/s in an eye and the contralateral eye unaffected, enucleated or without tumor activity. In both cases, relapsed or refractory vitreous seeding with the use of systemic, intraarterial or intravitreal chemotherapy or radiotherapy, in accordance with the availability at his/her referral site, in whom enucleation is the only recommended treatment under opinion of the medical team treating the case at the originating referral site. But the patient has a strong desire to preserve the eye.
- •Normal renal function: serum creatinine: < 45 μmol/L (0-2 years); < 57 μmol/L (3-6 years); < 60 μmol/L (7-10 years); < 80 μmol/L (11-13 years).
- •Normal Hepatic function: serum ALT: < 0,52 μkat/L (de 9 months -12 years); serum AST: 61-80 g/L (8 months-5 years); 63-83 g/L (5-9 years); 63-82 g/L (9-12 years).
- •Adequate marrow reserve manifested in an absolute neutrophil count > 1000 / mm3, platelets > 100,000 / mm3 and hemoglobin> 8 g / dl, without transfusional or cytokine support at least one month prior to study entry.
- •Age greater than 1 year and less than 12 years at the time of inclusion in the study.
- •Sign the informed consent form and be willing to follow up at the specified time.
排除标准
- •Presence of factors that require immediate enucleation of the affected eye such as glaucoma, rubeosis iridis, anterior chamber involvement.
- •Comorbidities: Uncontrolled epilepsy with anticonvulsant treatment, cardiac disease not compensated by treatment.
- •Active Infections.
- •Other chronic or active acute diseases that under the criterion of the researcher were an exclusion criterion.
- •History of having received attenuated or live vaccines in the 30 days prior to inclusion in the study.
- •Any cause of Immunosuppression.
- •Trilateral Retinoblastoma.
- •Extraocular spread.
- •History of having received treatment for retinoblastoma with chemotherapy or radiation therapy by any means within 30 days prior to inclusion in the study.
- •Patients who can not complete the study procedures for reasons psychologically or socially
研究组 & 干预措施
High-dose Topotecan for Retinoblastoma With Recurrent or Refractory Vitreous Seed
Intravitreal injection of topotecan at a dosage of 100μg was performed on day 1 of week 1.The frequency of treatment is personalized by ophthalmologists based on the intraocular stage of RB and treatment response. The criteria for end event are complete disappearance of vitreous seeding or stable calcification. Patients were followed up and evaluated every four weeks, with collection of aqueous humor and electroretinogram examination.
干预措施: Topotecan (Drug)
High-dose Topotecan for Retinoblastoma With Recurrent or Refractory Vitreous Seed
Intravitreal injection of topotecan at a dosage of 100μg was performed on day 1 of week 1.The frequency of treatment is personalized by ophthalmologists based on the intraocular stage of RB and treatment response. The criteria for end event are complete disappearance of vitreous seeding or stable calcification. Patients were followed up and evaluated every four weeks, with collection of aqueous humor and electroretinogram examination.
干预措施: Collection of aqueous humor (Other)
High-dose Topotecan for Retinoblastoma With Recurrent or Refractory Vitreous Seed
Intravitreal injection of topotecan at a dosage of 100μg was performed on day 1 of week 1.The frequency of treatment is personalized by ophthalmologists based on the intraocular stage of RB and treatment response. The criteria for end event are complete disappearance of vitreous seeding or stable calcification. Patients were followed up and evaluated every four weeks, with collection of aqueous humor and electroretinogram examination.
干预措施: Electroretinogram (Other)
结局指标
主要结局
Tumor response
时间窗: 28 days
Tumor response rate (ORR) to Topotecan at 28 days post-administration.
次要结局
- Incidence of Treatment-Emergent Adverse Events(13 weeks)
- Immune response(13 weeks)
- Electroretinogram(13 weeks)