A Study to Give Treatment Inside the Eye to Treat Retinoblastoma
Intravitreal Melphalan for Intraocular Retinoblastoma
3 other identifiers
interventional
26
3 countries
20
Brief Summary
This phase II trial tests the safety and side effects of adding melphalan (by injecting it into the eye) to standard chemotherapy in early treatment of patients with retinoblastoma (RB). RB is a type of cancer that forms in the tissues of the retina (the light-sensitive layers of nerve tissue at the back of the eye). It may be hereditary or nonhereditary (sporadic). RB is considered harder to treat (higher risk) when there are vitreous seeds present. Vitreous seeds are RB tumors in the jelly-like fluid of the eye (called the vitreous humor). The term, risk, refers to the chance of the cancer not responding to treatment or coming back after treatment. Melphalan is in a class of medications called alkylating agents. It may kill cancer cells by damaging their deoxyribonucleic acid (DNA) and stopping them from dividing. Other chemotherapy drugs given during this trial include carboplatin, vincristine, and etoposide. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Adding melphalan to standard chemotherapy early in treatment may improve the ability to treat vitreous seeds and may be better than standard chemotherapy alone in treating retinoblastoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Nov 2022
Longer than P75 for phase_2
20 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 4, 2022
CompletedFirst Posted
Study publicly available on registry
August 17, 2022
CompletedStudy Start
First participant enrolled
November 4, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 31, 2028
February 17, 2026
February 1, 2026
5.4 years
August 4, 2022
February 12, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Feasibility success rate of intravitreal melphalan injection in combination with systemic chemotherapy
A patient will be considered to have experienced intravitreal injection feasibility success if intravitreal melphalan can be delivered by cycle 6. If the treating physician does not inject because the eye has a full complete response (CR) for vitreous seeds after 2 cycles of systemic chemotherapy, it will be counted as a success in the feasibility analysis. Any feasibility evaluable patient who does not experience feasibility success will be considered a feasibility failure. For a bilateral patient with two Group D eyes with vitreous seeds, he/she will be categorized based on the worse results with the intent of being conservative, i.e., if intravitreal melphalan can be delivered in one eye but not the other by cycle 6 for any reason other than a CR of vitreal seeds, the patient will be deemed as experiencing a failure.
Up to cycle 6 (1 cycle = 28 days)
Secondary Outcomes (2)
Percentage of patients with grade 3 or higher toxicities
Up to 30 days after last dose of study treatment
Event-free survival (EFS)
Up to 5 years
Other Outcomes (6)
Retrospective central review of examination under anesthesia and ultrasound biomicroscopy images
Cycle 3 or later(1 cycle = 28 days)
Validate and standardize the aqueous humor extraction, storage, and collection protocols across multiple centers
Up to 5 years
Highly-recurrent RB somatic copy number alterations (SCNAs) tumor fraction
Up to 5 years
- +3 more other outcomes
Study Arms (1)
Treatment (CVE, melphalan)
EXPERIMENTALSee Detailed Description
Interventions
Given IV
Undergo aqueous humor, tissue, and blood sample collection
Given IV
Undergo imaging of the eye during EUA
Undergo MRI
Given I-VITRE
Undergo UBM during EUA
Given IV
Eligibility Criteria
You may qualify if:
- Patient must be \< 18 years of age at enrollment
- Patient must have newly diagnosed intraocular (localized) retinoblastoma and meet one of the following criteria:
- Unilateral Group D retinoblastoma with vitreous seeding; OR
- Bilateral retinoblastoma with worst eye Group D, with vitreous seeding present and the contralateral eye is Group A-C; OR
- Bilateral Group D retinoblastoma with at least one eye with vitreous seeding; OR
- Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\<16 years of age
- Peripheral absolute neutrophil count (ANC) \>= 750/uL (must be performed within 7 days prior to enrollment unless otherwise indicated)
- Platelet count \>= 75,000/uL (transfusion independent) (must be performed within 7 days prior to enrollment)
- A serum creatinine based on age/sex as follows (must be performed within 7 days prior to enrollment; must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment):
- month to \< 6 months = 0.4 (male and female)
- months to \< 1 year = 0.5 (male and female)
- to \< 2 years = 0.6 (male and female)
- to \< 6 years = 0.8 (male and female)
- to \< 10 years = 1.0 (male and female)
- to \< 13 years = 1.2 (male and female)
- +8 more criteria
You may not qualify if:
- Patients with evidence of metastatic or extra-orbital spread
- Patients must not have an invasive infection at time of protocol entry
- Patients must not have had any prior anti-cancer therapy other than cryotherapy and/or laser therapy (green or infrared) to the study eye(s) and non-study eye, including systemic chemotherapy, intra-arterial chemotherapy, radioactive plaque, brachytherapy, or radiation therapy.
- Note: A study eye is defined as being Group D with vitreous seeding. Patients may have had enucleation of one eye as long as the remaining eye is Group D with vitreous seeds
- Patients with bilateral disease who undergo enucleation of a Group E eye prior to initiation of therapy and show evidence of high-risk histopathology features in the enucleated eye. High-risk histopathology includes choroid involvement \>= 3 mm, post lamina optic nerve involvement, full thickness scleral invasion or optic nerve invasion to the cut end
- Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
- Lactating females who plan to breastfeed their infants
- Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
- All patients and/or their parents or legal guardians must sign a written informed consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (20)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Primary Children's Hospital
Salt Lake City, Utah, 84113, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Royal Children's Hospital
Parkville, Victoria, 3052, Australia
Perth Children's Hospital
Perth, Western Australia, 6009, Australia
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Rachana Shah
Children's Oncology Group
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 4, 2022
First Posted
August 17, 2022
Study Start
November 4, 2022
Primary Completion (Estimated)
March 31, 2028
Study Completion (Estimated)
March 31, 2028
Last Updated
February 17, 2026
Record last verified: 2026-02