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Recruiting Phase 2

A Study to Give Treatment Inside the Eye to Treat Retinoblastoma

NCT05504291 · tracked via the Priya Life Science Australia tracker
Phase
Phase 2
Started
2022-11-04
Last updated
2026-08-25

Condition(s) studied

Bilateral RetinoblastomaChildhood Intraocular RetinoblastomaGroup D RetinoblastomaStage I RetinoblastomaUnilateral Retinoblastoma

Investigational drug(s) / intervention(s)

Biospecimen CollectionCarboplatin →Etoposide →Examination Under AnesthesiaMagnetic Resonance ImagingMelphalan →Ultrasound BiomicroscopyVincristine →

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

Study 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.

Eligibility

Sex
ALL
Min age
—
Max age
18 Years
Healthy volunteers
No
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

Primary outcome measure(s)

  • Feasibility success rate of intravitreal melphalan injection in combination with systemic chemotherapy — Up to cycle 6 (1 cycle = 28 days)
    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.

Trial sites (20)

FacilityCityRegionStatus
Children's Hospital of Alabama Birmingham Alabama Recruiting
Children's Hospital Los Angeles Los Angeles California Recruiting
Lucile Packard Children's Hospital Stanford University Palo Alto California Recruiting
Children's Hospital Colorado Aurora Colorado Recruiting
Children's Healthcare of Atlanta - Arthur M Blank Hospital Atlanta Georgia Recruiting
C S Mott Children's Hospital Ann Arbor Michigan Recruiting
Washington University School of Medicine St Louis Missouri Recruiting
Duke University Medical Center Durham North Carolina Recruiting
Children's Hospital Medical Center of Akron Akron Ohio Recruiting
Cleveland Clinic Foundation Cleveland Ohio Recruiting
Saint Jude Children's Research Hospital Memphis Tennessee Recruiting
Dell Children's Medical Center of Central Texas Austin Texas Recruiting
UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas Recruiting
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center Houston Texas Recruiting
UT MD Anderson Cancer Center Houston Texas Recruiting
Primary Children's Hospital Salt Lake City Utah Withdrawn
Children's Hospital of Wisconsin Milwaukee Wisconsin Recruiting
Royal Children's Hospital Parkville Victoria Suspended
Perth Children's Hospital Perth Western Australia Suspended
Centre Hospitalier Universitaire Sainte-Justine Montreal Quebec Recruiting
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05504291 on ClinicalTrials.gov ↗ ← All trials in Australia