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

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.

Study Overview

• Status: Completed
• Conditions: Retinoblastoma
• Intervention / Treatment: Drug: Carboplatin; Drug: Maxitrol®; Procedure: Focal Therapy; Procedure: Plaque Radiotherapy

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 Aqueous fluid (0.1-0.15ml) will be withdrawn and sent for pathology review.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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Refractory or recurrent retinoblastoma with vitreous seeding meeting eligibility criteria by ultrasonic biomicroscopy performed during examination under anesthesia (EUA) by an ophthalmologist:

  • At least three consecutive clock hours of disease-free, attached peripheral retina through which the intraocular injection may be administered.
  • Absence of invasion in anterior and posterior chamber.
  • Absence of anterior hyaloid detachment.
  • Absence of retinal detachment at the entry site.
  • Absence of tumor at the entry site.
• ECOG Performance Score must be ≤ 2 within two weeks prior to registration.
• Participants must have an adequate liver function, as defined by bilirubin ≤3 x upper limit of normal (ULN), and SGOT and SGPT ≤3 x ULN.
• Participants must have adequate renal function as defined by serum creatinine ≤3 x ULN for age.
• Legal guardians must sign an informed consent indicating that they are aware of this study, the possible benefits, and toxic side effects. Legal guardians will be given a signed copy of the consent form.

Exclusion Criteria:

• Presence of metastatic disease or gross orbital involvement.
• Participants must not have an invasive infection at time of protocol entry.
• Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment; Participants with retinoblastoma that is refractory or has relapsed inside the eye. Interventions: Carboplatin, Maxitrol® , focal therapy, plaque radiotherapy.

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).; Other Names: Paraplatin®; 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.; Other Names: Anti-infective; 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.; Other Names: Laser photocoagulation; Cryotherapy; Thermo-therapy; 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.; Other Names: Brachytherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants who develop dose-limiting toxicity (DLT)	DLTs are defined as any of the following: uveitis, sterile or infectious endophthalmitis, retinopathy or rhegmatogenous retinal detachment, massive vitreous hemorrhage that obscures direct visualization of the retina/tumor, and/or cataract that threatens the visual axis or view by treating physician. Grade 3 or 4 allergic reactions should lead to discontinuation of intravitreal carboplatin injections. Patients who have grade 3 or 4 allergic reactions will not be evaluable for this objective and will be replaced.	From baseline through end of therapy (up to 5 months)

Collaborators and Investigators

• Sponsor: St. Jude Children's Research Hospital
• Investigators: Principal Investigator: Rachel Brennan, MD, St. Jude Children's Research Hospital

Publications and helpful links

Helpful Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Actual): October 4, 2019
• Study Completion (Actual): October 4, 2019

Study Registration Dates

• First Submitted: June 2, 2016
• First Submitted That Met QC Criteria: June 2, 2016
• First Posted (Estimate): June 7, 2016

Study Record Updates

• Last Update Posted (Actual): February 20, 2020
• Last Update Submitted That Met QC Criteria: February 19, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Eye Diseases; Retinal Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Eye Diseases, Hereditary; Eye Neoplasms; Retinal Neoplasms; Retinoblastoma; Antineoplastic Agents; Carboplatin
• Other Study ID Numbers: iRET; NCI-2016-00848 (Registry Identifier: NCI Clinical Trial Registration Program)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No