Targeting NUDT21 siRNA Drugs for Patients With Refractory Retinoblastoma

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Targeting NUDT21 siRNA Drugs for Patients With Refractory Retinoblastoma

Study Purpose

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 Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	1 Year - 12 Years
Gender	All

More Inclusion & Exclusion 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 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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06424301
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Early Phase 1
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Eye & ENT Hospital of Fudan University
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Jiang Qian, MDKang Xue, MDKang Zhang, MD
Principal Investigator Affiliation	Fudan Eye & ENT HospitalFudan Eye & ENT HospitalThe Eye Hospital of Wenzhou Medical University
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Retinoblastoma, Refractory

Arms & Interventions

Arms

Experimental: Intravitreal chemotherapy in patients with refractory retinoblastoma

The enrolled patients underwent blood sample collection and clinical evaluation before the first injection of the targeted drug. Intravitreal injection of the targeted drug at a dosage of 100-1000 μg was performed on day 1 of week 1 and week 3, respectively. Collection of aqueous humor was performed on weeks 1, 3, and 7, respectively. Collection of blood samples and sputum specimens was performed on weeks 1, 3, 5, and 7. And clinical assessment was performed weekly with continuous follow-up until 12 weeks.