Targeting NUDT21 siRNA Drugs for Patients With Refractory Retinoblastoma

NCT06424301 | Recruiting Early Phase 1 DMC

• 1 other identifier: FDEENT-20241031
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

Retinoblastoma (RB) is the most common intraocular malignancy in children, accounting for approximately 11% of all cancers diagnosed in children under the age of one. Although its incidence is relatively low-about 1 in 15,000 to 20,000 live births-RB has a high risk of intracranial metastasis via the optic nerve, often leading to poor prognosis in advanced cases. Recent advances in administration routes, such as intravitreal and intra-arterial chemotherapy, have significantly improved eye preservation rates. However, these strategies are limited by cumulative retinal toxicity and drug resistance. In refractory cases, enucleation remains the only definitive treatment to prevent extraocular spread and death. In light of these challenges, current research efforts are focused on developing novel targeted therapies that enhance anti-tumor efficacy while minimizing local toxicity. In this context, we introduce a first-in-class siRNA-based drug targeting NUDT21, which promotes tumor regression by modulating the 3'UTR tail of SMC1A, thereby suppressing tumor cell proliferation. Importantly, the siRNA drug selectively targets tumor cells, offering a favorable safety profile compared to conventional chemotherapeutic regimens. Given that both the target (NUDT21) and the mode of administration (intraocular siRNA injection) are novel in retinoblastoma treatment, there is an urgent need for early-phase investigator-initiated clinical research. This study is therefore designed to assess the short-term safety and preliminary efficacy of NUDT21 siRNA in patients with refractory retinoblastoma, and to provide an evidence base for future large-scale clinical trials.

Conditions

Retinoblastoma; Refractory

Keywords

retinoblastoma; intravitreal Chemotherapy

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

  Treatment-emergent adverse events (TEAEs) are defined as any unfavorable or unintended sign, symptom, or disease temporally associated with the administration of intravitreal siRNA therapy, whether or not considered related to the drug. Use CTCAE v5.0 (Common Terminology Criteria for Adverse Events) for grading severity.

  6 months

Secondary Outcomes (3)

• Tumor size

  6 months

• Retinal function

  6 months

• Target engagement

  6 months

Study Arms (1)

Intravitreal chemotherapy in patients with refractory retinoblastoma

EXPERIMENTAL

Prior to the first administration of the targeted drug, enrolled patients underwent peripheral blood sampling and comprehensive clinical evaluation. Intravitreal injections of the targeted drug were administered at a dosage of 100-200 μg (100 μg for patients under 2 years of age; 200 μg for patients aged 2 years and above) on Day 1 of Weeks 1, 3, and 7. Aqueous humor samples were collected at the time of injection during Weeks 1, 3, and 7. Clinical assessments were conducted monthly, with continuous follow-up extending through Week 24.

Drug: Targeting NUDT21 siRNA drugs

Interventions

Targeting NUDT21 siRNA drugs DRUG

It is performed for intravitreal chemotherapy.

Intravitreal chemotherapy in patients with refractory retinoblastoma

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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 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).
• 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.

Sponsors & Collaborators

• Eye & ENT Hospital of Fudan University: lead
• The Eye Hospital of Wenzhou Medical University: collaborator

Study Sites (1)

Fudan Eye & ENT Hospital

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Retinoblastoma

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

Study Officials

• Chen Zhao, MD

  Fudan Eye & ENT Hospital

  PRINCIPAL INVESTIGATOR

• Kang Xue, MD

  Fudan Eye & ENT Hospital

  STUDY DIRECTOR

• Kang Zhang, MD

  The Eye Hospital of Wenzhou Medical University

  STUDY DIRECTOR

• Jiang Qian, MD

  Fudan Eye & ENT Hospital

  STUDY DIRECTOR

Central Study Contacts

Chen Zhao, MD

CONTACT

86-021-64377134; dr_zhaochen@fudan.edu.cn

Ruiqi Ma, MD

CONTACT

ruiqi_ma@fudan.edu.cn

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 16, 2024
• First Posted: May 22, 2024
• Study Start: December 20, 2024
• Primary Completion: September 30, 2025
• Study Completion: September 30, 2025
• Last Updated: June 26, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE

Locations

CN (1)