Intrathecal Chemotherapy for Central Nervous System Metastasis in Retinoblastoma

Intrathecal Chemotherapy for Central Nervous System Metastasis in Retinoblastoma (A Multicenter Prospective Single Arm Trial)

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.

Study Overview

• Status: Recruiting
• Conditions: Retinoblastoma, Extraocular
• Intervention / Treatment: Drug: Melphalan

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jiang Qian, MD; Phone Number: +86 (021) 64377134; Email: qianjiang@fudan.edu.cn

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Fudan Eye & ENT Hospital
    • Contact: Jiang Qian, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 1.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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: intrathecal chemotherapy in patients with central metastases; 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; Melphalan is performed for intrathecal chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival at 2-year interval	living subjects	2 years
overall survival at 5-year interval	living subjects	5 years
disease-free survival at 2-year interval	tumor-free subjects	2 years
disease-free survival at 5-year interval	tumor-free subjects	5 years
progression-free survival	living subjects	1 year
response rate	tumor-free subjects	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Arachnoiditis	A disorder characterized by inflammation of the arachnoid membrane and adjacent subarachnoid space.	2 years
Number of Participants with Encephalopathy	A disorder characterized by a pathologic process involving the brain.	5 years
Number of Participants with Headache	A disorder characterized by a sensation of marked discomfort in various parts of the head, not confined to the area of distribution of any nerve.	2 years
Number of Participants with Encephalomyelitis infection	A disorder characterized by an infectious process involving the brain and spinal cord tissues.	1 year
Health-Related Quality of life	The health-related quality of life will be assessed based on the EORTC (European Organisation for Research and Treatment of Cancer) Quality of Life Questionnaire Core 30 (QLQ-C30) downloaded from https://www.eortc.org. This 30-item questionnaire includes five functional scales, three symptom scales, a global health status / QoL scale, and six single items. The multi-item scales include a different set of items. Each item includes four subscales, namely "Not at all" (1 point), "A little" (2 points), "Quite a bit" (3 points) and "Very much" (4 points)	10 years
Ophthalmic Cancer-Related Quality of life	The ophthalmic cancer-related quality of life will be assessed based on the EORTC (European Organisation for Research and Treatment of Cancer) Quality of Life Questionnaire Ophthalmic Cancer Module 30 (QLQ-OPT30) - Page 4 of 6 [DRAFT] - downloaded from https://www.eortc.org. The QLQ-OPT30 comprises of 30 questions assessing vision impairment (9 items), functional problems due to vision impairment (8 items), eye symptoms (6 items), worry about recurrent disease (2 items), problems with appearance (1 items), problems driving (2 items), headache (1 item), problems reading (1 item). Each item includes four subscales, namely "Not at all" (1 point), "A little" (2 points), "Quite a bit" (3 points) and "Very much" (4 points).	10 years

Collaborators and Investigators

• Sponsor: Eye & ENT Hospital of Fudan University
• Collaborators: Zhongshan Ophthalmic Center, Sun Yat-sen University; Children's Hospital of Fudan University
• Investigators: Principal Investigator: Jiang Qian, MD, Fudan Eye & ENT Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2021
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2030

Study Registration Dates

• First Submitted: May 22, 2021
• First Submitted That Met QC Criteria: May 22, 2021
• First Posted (Actual): May 26, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 24, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: retinoblastoma; central metastases; intrathecal Chemotherapy
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Eye Diseases; Neoplasms, Glandular and Epithelial; Neoplastic Processes; Eye Diseases, Hereditary; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Eye Neoplasms; Retinal Diseases; Retinal Neoplasms; Neoplasm Metastasis; Retinoblastoma; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Melphalan
• Other Study ID Numbers: FD-EENT-2021056

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No