Targeting NUDT21 siRNA Drugs for Patients With Refractory Retinoblastoma

Retinoblastoma Clinical Trial

Official title:

Targeting NUDT21 siRNA Drugs for Patients With Refractory Retinoblastoma (A Two-center Prospective Single Arm Trial)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06424301
• Other study ID #: FD-EENT-20240221
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: May 21, 2024
• Est. completion date: May 21, 2027

Study information

• Verified date: May 2024
• Source: Eye & ENT Hospital of Fudan University
• Contact: Ruiqi Ma, MD
• Phone: 86-021-64377134
• Email: ruiqi_ma[@]fudan.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Retinoblastoma (RB) is the most common intraocular malignancy in children and accounts for 11% of all cancers in children under the age of 1 year. Although the incidence of RB is low, approximately 1/15,000 ~ 1/20,000, it tends to metastasize to the intracranial area through the optic nerve pathway leading to poor prognosis for patients with RB. Currently, with the emergence of new administration routes, such as intravitreal and intrarterial chemotherapy, 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 to increase anti-tumor activity and reduce side effects. In this study, a novel targeting NUDT21 siRNA drug will be used to treat patients with refractory retinoblastoma. This drug promotes tumor apoptosis by regulating the 3'UTR plus tail of SMC1A, which makes the proliferative activity of tumor cells weaken and achieves tumor control. At the same time, since the targeted drug only focuses on tumor cells, it has reduced side effects compared with existing local chemotherapy regimens.

Based on the above background, this study will explore the feasibility and effectiveness of intravitreal injection of NUDT21 siRNA in patients with refractory retinoblastoma through a two-center prospective study.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: May 21, 2027
• Est. primary completion date: May 21, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 12 Years

Eligibility

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 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 psychological or Social.

Related Conditions & MeSH terms

• Refractory
• Retinoblastoma

Intervention

Drug:
• Targeting NUDT21 siRNA drugs
It is performed for intravitreal chemotherapy.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Eye & ENT Hospital of Fudan University	The Eye Hospital of Wenzhou Medical University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment-Emergent Adverse Events		49 days
Secondary	Tumor response	Tumor response rate (ORR) to targeting NUDT21 siRNA at 28 days post-administration.	28 days
Secondary	Targeting NUDT21 siRNA drugs	To detect the presence of drugs in blood samples and aqueous humor. To find out the difference in drug concentrations before and after treatment to evaluate the excretion profile of the drug.	49 days
Secondary	Immune response	Inflammatory factor testing was performed on the patients' aqueous humor samples.	49 days