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

NCT02792036 | Completed Phase 1 FDA Drug

• 2 other identifiers: iRETNCI-2016-00848
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Retinoblastoma

Outcome Measures

Primary Outcomes (1)

• 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)

Study Arms (1)

Treatment

EXPERIMENTAL

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

Drug: Carboplatin; Drug: Maxitrol®; Procedure: Focal Therapy; Procedure: Plaque Radiotherapy

Interventions

Carboplatin DRUG

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).

Also known as: Paraplatin®

Treatment

Maxitrol® DRUG

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.

Also known as: Anti-infective

Treatment

Focal Therapy PROCEDURE

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.

Also known as: Cryotherapy, Laser photocoagulation, Thermo-therapy

Treatment

Plaque Radiotherapy PROCEDURE

Participants who have developed progressive disease despite focal (non-irradiative) therapy will receive brachytherapy determined by consensus between the treating ophthalmologist and radiation oncologist.

Also known as: Brachytherapy

Treatment

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

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

MeSH Terms

Conditions

Retinoblastoma

Interventions

Carboplatin; Maxitrol; Anti-Infective Agents; Cryotherapy; Brachytherapy

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Retinal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases, Hereditary; Eye Diseases; Retinal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Therapeutics; Radiotherapy

Study Officials

• Rachel Brennan, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2016
• First Posted: June 7, 2016
• Study Start: November 1, 2016
• Primary Completion: October 4, 2019
• Study Completion: October 4, 2019
• Last Updated: February 20, 2020

Record last verified: 2020-02

Locations

US (1)