IRB Study Number 22-1212
Status Recruiting
Institute Taussig Cancer Institute
Description
1.1 Primary Objective
1.1.1 To determine the feasibility of administering intravitreal melphalan by Cycle 6 when given in combination with systemic CVE for the treatment of Group D retinoblastoma with vitreous seeding.
1.2 Secondary Objectives
1.2.1 To determine the safety and toxicity profile associated with intravitreal melphalan in combination with systemic CVE for the treatment of Group D retinoblastoma with vitreous seeding.
1.2.2 To evaluate the efficacy of intravitreal melphalan in conjunction with systemic chemotherapy in Group D intraocular retinoblastoma with vitreous seeding.
Inclusion Criteria
3.2.1 Age
Patient must be <18 years of age at enrollment.
3.2.2 Diagnosis
3.2.2.1 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 (See Section 3.2.9).
3.2.3 Performance Level
Patients must have a performance status corresponding to ECOG scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients ≤ 16 years of age.
3.2.4 Organ Function Requirements
3.2.4.1 Adequate Bone Marrow Function Defined As:
Peripheral absolute neutrophil count (ANC) 750/L
Platelet count 75,000/L (transfusion independent)
3.2.4.2 Adequate Renal Function Defined As:
- A serum creatinine based on age/gender as follows: (See protocol)
OR - a 24-hour urine Creatinine clearance ≥ 70 mL/min/1.73 m2
OR - a GFR ≥ 70 mL/min/1.73 m2. 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 ULN for patients <1 month of age or the creatinine clearance or radioisotope GFR must be ≥70 mL/min/1.73 m2
3.2.4.3 Adequate Liver Function Defined As:
Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age, and
SGPT (ALT) ≤ 135 U/L
Exclusion Criteria
3.2.5 Patients with evidence of metastatic or extra-orbital spread.
3.2.6 Patients must not have an invasive infection at time of protocol entry.
3.2.7 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.
3.2.8 Patients with no reasonable expectation for any useful vision in the Group D eye as determined by the treating physician.
3.2.9 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.
3.2.10 Pregnancy and Breastfeeding
3.2.10.1 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.
3.2.10.2 Lactating females who plan to breastfeed their infants.
3.2.10.3 Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.
3.2.11 Regulatory Requirements
3.2.11.1 All patients and/or their parents or legal guardians must sign a written informed consent.
3.2.11.2 All institutional, FDA, and NCI requirements for human studies must be met.
