A Study to Give Treatment Inside the Eye to Treat Retinoblastoma

Launched by CHILDREN'S ONCOLOGY GROUP · Aug 15, 2022

Keywords

ClinConnect Summary

This clinical trial is studying a new way to treat retinoblastoma, a type of eye cancer that occurs in young children. The researchers want to see if adding a medication called melphalan, which is injected directly into the eye, can make standard chemotherapy more effective, especially for patients who have tumors in the jelly-like fluid of the eye, known as vitreous seeds. This trial is for children and young adults under 18 who have been newly diagnosed with specific forms of retinoblastoma that involve these vitreous seeds.

Participants in the trial will receive melphalan along with standard chemotherapy treatments, which include other medications that help fight cancer. Before joining, patients will need to meet certain health criteria to ensure it's safe for them. Throughout the trial, doctors will closely monitor participants for any side effects and how well the treatment is working. This research could potentially lead to better treatment options for children facing this challenging condition.

Gender

ALL

Eligibility criteria

• 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