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

NCT06972602 | Recruiting Early Phase 1

• 1 other identifier: FD-EENT-2018044-1
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Retinoblastoma; Retinoblastoma, Recurrent

Outcome Measures

Primary Outcomes (1)

• Tumor response

  Tumor response rate (ORR) to Topotecan at 28 days post-administration.

  28 days

Secondary Outcomes (3)

• Incidence of Treatment-Emergent Adverse Events

  13 weeks

• Immune response

  13 weeks

• Electroretinogram

  13 weeks

Study Arms (1)

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

EXPERIMENTAL

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.

Drug: Topotecan; Other: Collection of aqueous humor; Other: Electroretinogram

Interventions

Topotecan DRUG

Intravitreal injection of topotecan at a dosage of 100μg was performed at week 1.Then based on the tumor response and vitreous seeding, it will be decided whether to continue the injection by ophthalmologists.

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

Collection of aqueous humor OTHER

Patients' aqueous humor samples will be collected for Inflammatory factor testing and IOP control every 4 weeks.

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

Electroretinogram OTHER

Electroretinogram was performed every 4 weeks.

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

Eligibility Criteria

• Age: 1 Year - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• Sign the informed consent form and be willing to follow up at the specified time.

You may not qualify if:

• 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.
• Any cause of Immunosuppression.
• Trilateral Retinoblastoma.
• Extraocular spread.
• Patients who can not complete the study procedures for reasons psychologically or socially

Sponsors & Collaborators

• Eye & ENT Hospital of Fudan University: lead

Study Sites (1)

Fudan Eye & ENT Hospital

Shanghai, China, China

RECRUITING

MeSH Terms

Conditions

Retinoblastoma; Recurrence

Interventions

Topotecan

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Retinal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases, Hereditary; Eye Diseases; Retinal Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Central Study Contacts

Kang Xue, MD

CONTACT

+86 (021) 64377134; xuekang@foxmail.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2025
• First Posted: May 15, 2025
• Study Start: April 1, 2025
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2027
• Last Updated: May 15, 2025

Record last verified: 2025-05

Locations

CN (1)