## Protocol Section
### Identification Module
**NCT ID:** NCT06424301

**Brief Title:** Targeting NUDT21 siRNA Drugs for Patients With Refractory Retinoblastoma

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

#### Organization Study ID Info
**ID:** FD-EENT-20240221
#### Organization
**Class:** OTHER
**Full Name:** Eye & ENT Hospital of Fudan University
### Status Module
#### Completion Date
**Date:** 2027-05-21

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-22

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-16

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-05-21

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-21

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-22
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-16
**Study First Submit QC Date:** 2024-05-16
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** The Eye Hospital of Wenzhou Medical University

#### Lead Sponsor

**Class:** OTHER

**Name:** Eye & ENT Hospital of Fudan University

#### Responsible Party

**Investigator Affiliation:** Eye & ENT Hospital of Fudan University

**Investigator Full Name:** Chen Zhao

**Investigator Title:** Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**Brief 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.

### Conditions Module

**Conditions:**

- Retinoblastoma

- Refractory

**Keywords:**

- retinoblastoma

- intravitreal Chemotherapy

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 20

**Type:** ESTIMATED

**Phases:**

- EARLY_PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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.

**Intervention Names:**

- Drug: Targeting NUDT21 siRNA drugs

**Label:** Intravitreal chemotherapy in patients with refractory retinoblastoma

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Intravitreal chemotherapy in patients with refractory retinoblastoma

**Description:** It is performed for intravitreal chemotherapy.

**Name:** Targeting NUDT21 siRNA drugs

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Measure:** Incidence of Treatment-Emergent Adverse Events

**Time Frame:** 49 days

#### Secondary Outcomes

**Description:** Tumor response rate (ORR) to targeting NUDT21 siRNA at 28 days post-administration.

**Measure:** Tumor response

**Time Frame:** 28 days

**Description:** 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.

**Measure:** Targeting NUDT21 siRNA drugs

**Time Frame:** 49 days

**Description:** Inflammatory factor testing was performed on the patients' aqueous humor samples.

**Measure:** Immune response

**Time Frame:** 49 days

### Eligibility Module

**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 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.

**Maximum Age:** 12 Years

**Minimum Age:** 1 Year

**Sex:** ALL

**Standard Ages:**

- CHILD

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** ruiqi_ma@fudan.edu.cn

**Name:** Ruiqi Ma, MD

**Phone:** 86-021-64377134

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** Fudan Eye & ENT Hospital

**Name:** Jiang Qian, MD

**Role:** PRINCIPAL_INVESTIGATOR

**Official 2:**

**Affiliation:** Fudan Eye & ENT Hospital

**Name:** Kang Xue, MD

**Role:** PRINCIPAL_INVESTIGATOR

**Official 3:**

**Affiliation:** The Eye Hospital of Wenzhou Medical University

**Name:** Kang Zhang, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**Description:** IPD will be shared upon requirement.

**Info Types:**

- STUDY_PROTOCOL

- SAP

- ICF

- CSR

- ANALYTIC_CODE

**IPD Sharing:** YES

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000018302

- Term: Neoplasms, Neuroepithelial

- ID: D000017599

- Term: Neuroectodermal Tumors

- ID: D000009373

- Term: Neoplasms, Germ Cell and Embryonal

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000009375

- Term: Neoplasms, Glandular and Epithelial

- ID: D000009380

- Term: Neoplasms, Nerve Tissue

- ID: D000019572

- Term: Retinal Neoplasms

- ID: D000005134

- Term: Eye Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000015785

- Term: Eye Diseases, Hereditary

- ID: D000005128

- Term: Eye Diseases

- ID: D000012164

- Term: Retinal Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC11

- Name: Eye Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M15010

- Name: Retinoblastoma

- Relevance: HIGH

- As Found: Retinoblastoma

- ID: M20446

- Name: Neoplasms, Neuroepithelial

- Relevance: LOW

- As Found: Unknown

- ID: M19845

- Name: Neuroectodermal Tumors

- Relevance: LOW

- As Found: Unknown

- ID: M20388

- Name: Neuroectodermal Tumors, Primitive

- Relevance: LOW

- As Found: Unknown

- ID: M12318

- Name: Neoplasms, Germ Cell and Embryonal

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M12320

- Name: Neoplasms, Glandular and Epithelial

- Relevance: LOW

- As Found: Unknown

- ID: M12325

- Name: Neoplasms, Nerve Tissue

- Relevance: LOW

- As Found: Unknown

- ID: M21508

- Name: Retinal Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M8277

- Name: Eye Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M8271

- Name: Eye Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M18339

- Name: Eye Diseases, Hereditary

- Relevance: LOW

- As Found: Unknown

- ID: M14999

- Name: Retinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T4977

- Name: Retinoblastoma

- Relevance: HIGH

- As Found: Retinoblastoma

- ID: T4092

- Name: Neuroepithelioma

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000012175

- Term: Retinoblastoma

### Misc Info Module

- Version Holder: 2024-05-31
