Intrathecal Chemotherapy for Central Nervous System Metastasis in Retinoblastoma

NCT04903678 | Recruiting

• 1 other identifier: FD-EENT-2021056
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Retinoblastoma is the most common intraocular malignancy in infancy and childhood. The overall survival rate of retinoblastoma was reported to exceed 95% when children were early diagnosed with localized intraocular phase. The advanced retinoblastoma cases with central nervous system metastasis (CNS)is associated with exceedingly poor prognosis. CNS metastasis is the main cause of death in retinoblastoma. Meningeal involvement combined with spinal cord membrane involvement might be due to the meninges invasion and/or the spreading of CSF. As the most sensitive drug to retinoblastoma tumor cells in vitro, melphalan is the most important drug in the local treatment of retinoblastoma, and it is also an irreplaceable drug in the current eye preservation treatment, which greatly improves the success rate of eye preservation for advanced retinoblastoma. According to the research and the practice of vitreous injection (melphalan), the drug concentration in vitreous can effectively kill retinoblastoma tumor cells. It is reasonable to speculate that the tumor cells in CSF can be effectively killed by melphalan. Therefore, based on the above background, this study will explore the effectiveness and feasibility of intrathecal injection of melphalan in patients with CNS metastasis of retinoblastoma through a multicenter prospective study.

Conditions

Retinoblastoma, Extraocular

Keywords

retinoblastoma; central metastases; intrathecal Chemotherapy

Outcome Measures

Primary Outcomes (6)

• progression-free survival

  living subjects

  1 year

• overall survival at 2-year interval

  living subjects

  2 years

• overall survival at 5-year interval

  living subjects

  5 years

• response rate

  tumor-free subjects

  1 year

• disease-free survival at 2-year interval

  tumor-free subjects

  2 years

• disease-free survival at 5-year interval

  tumor-free subjects

  5 years

Secondary Outcomes (6)

• Number of Participants with Arachnoiditis

  2 years

• Number of Participants with Encephalopathy

  5 years

• Number of Participants with Headache

  2 years

• Number of Participants with Encephalomyelitis infection

  1 year

• Health-Related Quality of life

  10 years

Study Arms (1)

intrathecal chemotherapy in patients with central metastases

EXPERIMENTAL

Systemic chemotherapy and intrathecal chemotherapy are performed every 3 weeks. After three treatment cycles, the treatment response is comprehensively evaluated including cerebrospinal fluid, intracranial and orbital tumors. If necessary, local radiotherapy and arterial interventional chemotherapy are performed for local solid tumors. Cerebrospinal fluid is detected in each treatment cycle. If RB tumor cells still exist in cerebrospinal fluid, chemotherapy and intrathecal chemotherapy are continued until the end event. If cerebrospinal fluid was negative, intrathecal chemotherapy is supplemented for another 2 cycles with a total of 6 cycles of systemic chemotherapy. The patients are followed up after treatment.

Drug: Melphalan

Interventions

Melphalan DRUG

Melphalan is performed for intrathecal chemotherapy

intrathecal chemotherapy in patients with central metastases

Eligibility Criteria

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

You may qualify if:

• The pathological diagnosis was retinoblastoma. According to the IRSs (International retinoblastoma staging system) staging system, the stage was IVB
• CSF tumor cells on cytology, or radiographic evidence of NM on MRI scans and histologic diagnosis of systemic malignancy needed
• KPS≥60%
• Adequate bone marrow and organ function
• The parents signed the informed consent and were willing to accept the treatment and follow-up.

You may not qualify if:

• Eye diseases other than retinoblastoma
• The eyes were infected within 30 days before screening
• There was a history of surgery and / or unhealed wound within 1 month before enrollment .
• Those who have allergic reaction or allergic history to chemotherapeutic drugs.
• Infectious diseases requiring oral, intramuscular or intravenous administration.
• Patients with systemic immune diseases.
• Active disseminated intravascular coagulation.
• Abnormal coagulation function.
• Abnormal bone marrow and organ function.
• Uncontrollable clinical problems.
• The researchers believe that those who need to be excluded.

Sponsors & Collaborators

• Eye & ENT Hospital of Fudan University: lead
• Zhongshan Ophthalmic Center, Sun Yat-sen University: collaborator
• Children's Hospital of Fudan University: collaborator

Study Sites (1)

Fudan Eye & ENT Hospital

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Retinoblastoma

Interventions

Melphalan

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

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Jiang Qian, MD

  Fudan Eye & ENT Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jiang Qian, MD

CONTACT

+86 (021) 64377134; qianjiang@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 22, 2021
• First Posted: May 26, 2021
• Study Start: May 1, 2021
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2030
• Last Updated: February 25, 2025

Record last verified: 2025-02

Data Sharing

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

Locations

CN (1)