NCT02792036

Intravitreal Carboplatin for the Treatment of Participants With Recurrent or Refractory Intraocular Retinoblastoma

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 17 Years
• Healthy volunteers: Not accepted

Summary

Retinoblastoma (RB) is the most common intraocular tumor of childhood. Recurrent or refractory disease following therapy most often occurs due to persistence of vitreous disease and/or retinal reactivation of the main tumor mass. With this treatment protocol, investigators seek to identify a less invasive method of local drug delivery that does not disrupt the eye's integrity. PRIMARY OBJECTIVE: * To determine the safety and toxicity profile associated with intravitreal carboplatin for the treatment of recurrent or progressive intraocular retinoblastoma with vitreous seeding. SECONDARY OBJECTIVES: * To estimate the ocular salvage rate after treatment with intravitreal carboplatin in patients with recurrent or progressive intraocular retinoblastoma with vitreous seeding. * To evaluate the effects of intravitreal carboplatin therapy on the histopathology of eyes enucleated for progressive or recalcitrant disease while on therapy.

Detailed description

The eye(s) will be sterilized prior to injection. Aqueous fluid (0.1-0.15ml) will be withdrawn and sent for pathology review. Carboplatin diluted in normal saline will be administered via intravitreal injection under anesthesia once to each eligible eye approximately every 14 days. Following the injection, triple freeze/thaw cryotherapy is applied to the injection site and the eye is washed with water. The eye is gently "shaken" in all directions to evenly distribute the drug. This trial will use a traditional phase I design for dose de-escalation with two dose levels. The first 6 patients will be enrolled at dose level 1 and will be observed for dose-limiting toxicity (DLT) throughout the treatment period up to approximately 5 months after start of therapy. If 0-2 (of the first 6) participants experience DLT, a second cohort of 6 patients will be enrolled at the same dose level 1. Study accrual would be completed at 12. However, if 3 or more of the first 6 patients experience DLT at dose level 1, the dose level would be de-escalated to level -1 and 6 patients enrolled at this level (dose -1). If 0-2 patients experience DLT at dose level -1, a second cohort of 6 patients will be enrolled at dose level -1, and the study accrual would be complete. If 3 or more patients experience DLT at dose level -1, accrual would also be complete.

Conditions

• Retinoblastoma

Interventions

Type	Name	Description
DRUG	Carboplatin	Carboplatin will be given intravitreally. Participants are eligible to receive up to 8 injections per eye (once approximately every 14 days) based on lack of toxicity and evidence of tumor response. An injection of consolidation will be given once a complete response is observed. If further regression of "stable" seeds is noted, additional injections (up to 8 maximum per eye) will be provided at the discretion of the treating team. Injections could be repeated if vitreous recurrence occurs from another source (and patient has not reached 8 max limit per eye).
DRUG	Maxitrol®	Maxitrol® contains neomycin and polymyxin B sulfates and dexamethasone ophthalmic suspension and is for topical ophthalmic use only. It will be given for continued use for five days following the carboplatin injection to prevent infection.
PROCEDURE	Focal Therapy	Simultaneously with intravitreal carboplatin, focal therapy will be applied as needed to eradicate the retinal source of the seeding as well as all epiretinal and subretinal active tumors at the discretion of the treating ocular oncologist.
PROCEDURE	Plaque Radiotherapy	Participants who have developed progressive disease despite focal (non-irradiative) therapy will receive brachytherapy determined by consensus between the treating ophthalmologist and radiation oncologist.

Timeline

• Start date: 2016-11-01
• Primary completion: 2019-10-04
• Completion: 2019-10-04
• First posted: 2016-06-07
• Last updated: 2020-02-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study