High-dose Topotecan for Retinoblastoma With Recurrent or Refractory Vitreous Seed

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.

NCT Number	NCT06972602
Lead Sponsor	Eye & ENT Hospital of Fudan University
Conditions	Retinoblastoma, Retinoblastoma, Recurrent
Enrollment	10 participants
Start Date	2025-04-01
Primary Completion	2025-12-31 (estimated)
Study Completion	2027-12-31 (estimated)
Updated on ClinicalTrials.gov	2025-05-15