A Study to Give Treatment Inside the Eye to Treat Retinoblastoma

• Status: Not yet recruiting
• Trial end date: 2024-09-30
• Target enrollment: 0
• Participant gender: All

Summary

This phase II trial tests the safety and side effects of adding melphalan to standard chemotherapy in treating patients with retinoblastoma (RB). RB is a type of cancer that occurs in the eye. 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). The term, risk, refers to the chance of the cancer not responding to treatment or coming back after treatment. Chemotherapy drugs, such as melphalan, carboplatin, vincristine, and etoposide work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Melphalan is more commonly given later in therapy or in relapsed disease (cancer that has returned after treatment). Adding melphalan to standard chemotherapy early in treatment may improve the ability to treat vitreous seeds.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Children's Oncology Group
• Treatments: Carboplatin; Etoposide; Etoposide phosphate; Mechlorethamine; Melphalan; Nitrogen Mustard Compounds; Podophyllotoxin; Vincristine

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 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

• 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/gender 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

• 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 to the study eye(s), including focal, local, or systemic chemotherapy 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 no reasonable expectation for any useful vision in the Group D eye as determined by the treating physician

• 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