Recruiting

Phase 2

Melphalan Injection with Standard ChemotherapyRetinoblastomaA Study to Give Treatment Inside the Eye to Treat Retinoblastoma

Sponsor:

Children's Oncology Group

Code:

NCT05504291

Conditions

Bilateral Retinoblastoma

Childhood Intraocular Retinoblastoma

Group D Retinoblastoma

Stage I Retinoblastoma

Unilateral Retinoblastoma

Eligibility Criteria

Sex: All

Age: 0 - 18

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Carboplatin

Etoposide

Examination Under Anesthesia

Magnetic Resonance Imaging

Study Details

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.

Conditions

Bilateral Retinoblastoma

Childhood Intraocular Retinoblastoma

Group D Retinoblastoma

Stage I Retinoblastoma

Unilateral Retinoblastoma

Study ID

NCT05504291

Start date

Nov 4, 2022

Status verified date

Feb, 2026

Completion date

Mar 31, 2028

Anticipated

Primary completion date

Mar 31, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 0 - 18

Healthy Volunteers: Not accepted

Inclusion Criteria:

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
Bilateral retinoblastoma with one Group D eye with vitreous seeding and one Group E eye where the Group E eye has been enucleated prior to any therapy. Note exclusion for high-risk features
Bilateral retinoblastoma with one Group D eye with vitreous seeding and one Group E eye where the Group E eye has not been enucleated prior to any therapy at the discretion of the treating physician. Note exclusion for patients with evidence of metastatic or extra orbital spread
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):

1 month to < 6 months = 0.4 (male and female)
6 months to < 1 year = 0.5 (male and female)
1 to < 2 years = 0.6 (male and female)
2 to < 6 years = 0.8 (male and female)
6 to < 10 years = 1.0 (male and female)
10 to < 13 years = 1.2 (male and female)
13 to < 16 years = 1.5 (male) and 1.4 (female)
>= 16 years = 1.7 (male) and 1.4 (female) OR - a 24-hour urine Creatinine clearance >= 70 mL/min/1.73 m\^2 OR - a glomerular filtration rate (GFR) >= 70 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility

For patients < 1 month of age, serum creatinine levels must be < 1.5 x the treating institution's creatinine upper limit of normal (ULN) for patients < 1 month of age or the creatinine clearance or radioisotope GFR must be >= 70 mL/min/1.73 m\^2

The threshold creatinine values were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Center for Disease Control (CDC)
Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (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)
Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =< 135 U/L (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)

Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L

Exclusion Criteria:

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

Study Design

Enrollment

26 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (CVE, melphalan)

See Detailed Description

Interventions

Biospecimen Collection

Undergo aqueous humor, tissue, and blood sample collection

Carboplatin

Given IV

Etoposide

Given IV

Examination Under Anesthesia

Undergo imaging of the eye during EUA

Magnetic Resonance Imaging

Undergo MRI

Melphalan

Given I-VITRE

Ultrasound Biomicroscopy

Undergo UBM during EUA

Vincristine

Given IV

Primary outcome measure

Feasibility success rate of intravitreal melphalan injection in combination with systemic chemotherapy [ Time Frame: Up to cycle 6 (1 cycle = 28 days) ]

Central Contacts and Locations

Locations

Children's Hospital of Alabama

Recruiting

Birmingham, Alabama, United States, 35233

Contacts

Site Public Contact

205-638-9285 oncologyresearch@peds.uab.edu

Principal Investigator:

Elizabeth D. Alva

Children's Hospital Los Angeles

Recruiting

Los Angeles, California, United States, 90027

Contacts

Site Public Contact

323-361-4110

Principal Investigator:

Rachana Shah

Lucile Packard Children's Hospital Stanford University

Recruiting

Palo Alto, California, United States, 94304

Contacts

Site Public Contact

800-694-0012 ccto-office@stanford.edu

Principal Investigator:

Jay Michael S. Balagtas

Children's Hospital Colorado

Recruiting

Aurora, Colorado, United States, 80045

Contacts

Site Public Contact

303-764-5056 josh.b.gordon@nsmtp.kp.org

Principal Investigator:

Sandra Luna-Fineman

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Recruiting

Atlanta, Georgia, United States, 30329

Contacts

Site Public Contact

404-785-0232 Olivia.Floyd@choa.org

Principal Investigator:

Sarah G. Mitchell

C S Mott Children's Hospital

Recruiting

Ann Arbor, Michigan, United States, 48109

Contacts

Site Public Contact

800-865-1125

Principal Investigator:

Laura Sedig

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Site Public Contact

800-600-3606 info@siteman.wustl.edu

Principal Investigator:

Amy Armstrong

Duke University Medical Center

Recruiting

Durham, North Carolina, United States, 27710

Contacts

Site Public Contact

888-275-3853

Principal Investigator:

Jessica M. Sun

Children's Hospital Medical Center of Akron

Recruiting

Akron, Ohio, United States, 44308

Contacts

Site Public Contact

330-543-3193

Principal Investigator:

Erin Wright

Cleveland Clinic Foundation

Recruiting

Cleveland, Ohio, United States, 44195

Contacts

Site Public Contact

866-223-8100 TaussigResearch@ccf.org

Principal Investigator:

Matteo M. Trucco

Saint Jude Children's Research Hospital

Recruiting

Memphis, Tennessee, United States, 38105

Contacts

Site Public Contact

888-226-4343 referralinfo@stjude.org

Principal Investigator:

Carlos Rodriguez-Galindo

Dell Children's Medical Center of Central Texas

Recruiting

Austin, Texas, United States, 78723

Contacts

Site Public Contact

512-628-1902 TXAUS-DL-SFCHemonc.research@ascension.org

Principal Investigator:

Shannon M. Cohn

UT Southwestern/Simmons Cancer Center-Dallas

Recruiting

Dallas, Texas, United States, 75390

Contacts

Site Public Contact

214-648-7097 canceranswerline@UTSouthwestern.edu

Principal Investigator:

Daniel C. Bowers

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Site Public Contact

713-798-1354 burton@bcm.edu

Principal Investigator:

Murali M. Chintagumpala

UT MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Site Public Contact

866-632-6789 askmdanderson@mdanderson.org

Principal Investigator:

Najat C. Daw

Children's Hospital of Wisconsin

Recruiting

Milwaukee, Wisconsin, United States, 53226

Contacts

Site Public Contact

414-955-4727 MACCCTO@mcw.edu

Principal Investigator:

Kerri Becktell

Centre Hospitalier Universitaire Sainte-Justine

Recruiting

Montreal, Quebec, Canada, H3T 1C5

Contacts

Site Public Contact

514-345-4931 yvan.samson@umontreal.ca

Principal Investigator:

Monia Marzouki

More Information

Sponsor

Children's Oncology Group

Last update posted

Aug 25, 2026

Last verified

Feb, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Children's Oncology Group on 2026-08-25.