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

NCT ID: NCT06972602

Last Updated: 2025-05-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-01
• Study Completion Date: 2027-12-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Topotecan

Intervention Type: 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.

Collection of aqueous humor

Intervention Type: OTHER

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

Electroretinogram

Intervention Type: OTHER

Electroretinogram was performed every 4 weeks.

Interventions

Topotecan

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.

Intervention Type: DRUG

Collection of aqueous humor

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

Intervention Type: OTHER

Electroretinogram

Electroretinogram was performed every 4 weeks.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. 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.

2. 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).

3. 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).

4. 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.

5. Age greater than 1 year and less than 12 years at the time of inclusion in the study.

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

Exclusion Criteria

1. Presence of factors that require immediate enucleation of the affected eye such as glaucoma, rubeosis iridis, anterior chamber involvement.

2. Comorbidities: Uncontrolled epilepsy with anticonvulsant treatment, cardiac disease not compensated by treatment.

3. Active Infections.

4. Other chronic or active acute diseases that under the criterion of the researcher were an exclusion criterion.

5. History of having received attenuated or live vaccines in the 30 days prior to inclusion in the study.

6. Any cause of Immunosuppression.

7. Trilateral Retinoblastoma.

8. Extraocular spread.

9. History of having received treatment for retinoblastoma with chemotherapy or radiation therapy by any means within 30 days prior to inclusion in the study.

10. Patients who can not complete the study procedures for reasons psychologically or socially

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eye & ENT Hospital of Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Fudan Eye & ENT Hospital

Shanghai, China, China

Site Status: RECRUITING

Countries

China

Central Contacts

Kang Xue, MD

Role: CONTACT

xuekang@foxmail.com

+86 (021) 64377134

Facility Contacts

Kang Xue, MD

Role: primary

xuekang@foxmail.com

+86 (021) 64377134

Other Identifiers

FD-EENT-2018044-1

Identifier Type: -

Identifier Source: org_study_id