Intra-arterial Chemotherapy for Retinoblastoma (IAC)

Intra-arterial Chemotherapy for Retinoblastoma (IAC)

Children with retinoblastoma who may benefit from intra-arterial chemotherapy will receive up to 3 doses of melphalan and will be assessed for feasibility, toxicity, and response.

Study Overview

• Status: Active, not recruiting
• Conditions: Retinoblastoma
• Intervention / Treatment: Drug: Melphalan

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine (Saint Louis Children's Hospital)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients diagnosed with retinoblastoma >4 months of age16
• Patients whose other treatment options would require systemic chemotherapy, radiotherapy, or enucleation
• Patient or parent/legal guardian must sign a written informed consent

• One of a, b, or c:

  • Patients who have bilateral COG stage B, C, D, or E retinoblastoma (refer to Appendix A) who have undergone systemic chemotherapy without resolution (meaning either has not had CR or has progressed despite systemic chemotherapy) and would have the following treatment options remaining:

    • IAC
    • enucleation of one eye
    • local radiation
  • Patients with non-germline retinoblastoma with unilateral disease who have COG A, B, C, or D tumors (refer to Appendix A).
  • Other patients may be considered on a case by case basis after discussion with pediatric ophthalmology, hematology/oncology, and interventional neuroradiology.

Exclusion Criteria:

• Opaque or hazy media which precluded visualization of the fundus.
• New or recurrent retinoblastoma that can be controlled with other conservative measures such as cryotherapy, thermotherapy, or plaque radiotherapy.
• Unilateral COG group E retinoblastoma (refer to Appendix A) with very poor visual prognosis as defined by pediatric ophthalmologist.
• Patients who would benefit from systemic chemotherapy.
• Patients with clinical or radiological evidence suggestive of retinoblastoma invasion of the optic nerve, choroid, sclera, orbit or metastatic sites.
• Currently receiving any other investigational agents.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to melphalan or other agents used in the study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
• Pregnant and/or breastfeeding. Participants of childbearing potential must have a negative pregnancy test within 14 days of study entry.
• Patients with HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective ART according to DHHS treatment guidelines is recommended.

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: Intra-arterial injections of melphalan; -Participants will receive intra-arterial injections of melphalan Q4W for 3 cycles.	Drug: Melphalan; -The drug is commerically available; Other Names: Evomela

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of intra-arterial chemotherapy as measured by the number of participants who receive 3 intra-arterial injections of melphalan	-Feasibility is defined as the ability to receive 3 intra-arterial injections of melphalan per patient.	Completion of enrollment and treatment of all patients (estimated to be 32 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of procedure-related complications		Through 30 days following completion of treatment (estimated to be 4 months)
Rate of ocular salvage	A patient will be considered a successful ocular salvage if the child does not experience enucleation because of disease progression or toxicity during 2 years of follow-up.	2 years post-treatment
Visual acuity as measured by Cardiff testing		6 months post-treatment
Rate of metastatic disease	-Patients will be determined to have metastatic disease if they have received 1 or more administrations of IAC and they are found to have progression of disease or appearance of tumor outside of the eye after protocol therapy. Pineal tumors will not be considered metastatic disease.	Completion of treatment (estimated to be 3 months)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Margaret Reynolds, M.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2020
• Primary Completion (Actual): January 4, 2023
• Study Completion (Anticipated): January 4, 2025

Study Registration Dates

• First Submitted: April 8, 2020
• First Submitted That Met QC Criteria: April 8, 2020
• First Posted (Actual): April 13, 2020

Study Record Updates

• Last Update Posted (Actual): May 15, 2023
• Last Update Submitted That Met QC Criteria: May 11, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Eye Diseases; Retinal Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Eye Diseases, Hereditary; Eye Neoplasms; Retinal Neoplasms; Retinoblastoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Melphalan
• Other Study ID Numbers: 202006160

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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