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

Primary Purpose

Retinoblastoma

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Carboplatin

Maxitrol®

Focal Therapy

Plaque Radiotherapy

About this trial

This is an interventional treatment trial for Retinoblastoma

Eligibility Criteria

undefined - 17 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

St. Jude Children's Research Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT02792036

First Posted

June 2, 2016

Last Updated

February 19, 2020

Sponsor

St. Jude Children's Research Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02792036

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2020

Overall Recruitment Status

Completed

Study Start Date

November 1, 2016 (Actual)

Primary Completion Date

October 4, 2019 (Actual)

Study Completion Date

October 4, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

St. Jude Children's Research Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Retinoblastoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Other Intervention Name(s)

Paraplatin®

Intervention Description

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).

Intervention Type

Drug

Intervention Name(s)

Maxitrol®

Other Intervention Name(s)

Anti-infective

Intervention Description

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.

Intervention Type

Procedure

Intervention Name(s)

Focal Therapy

Other Intervention Name(s)

Cryotherapy, Laser photocoagulation, Thermo-therapy

Intervention Description

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.

Intervention Type

Procedure

Intervention Name(s)

Plaque Radiotherapy

Other Intervention Name(s)

Brachytherapy

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of participants who develop dose-limiting toxicity (DLT)

Description

Time Frame

From baseline through end of therapy (up to 5 months)

10. Eligibility

Sex

All

Maximum Age & Unit of Time

17 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Rachel Brennan, MD

Organizational Affiliation

St. Jude Children's Research Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

St. Jude Children's Research Hospital

City

Memphis

State/Province

Tennessee

ZIP/Postal Code

38105

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.stjude.org

Description

St. Jude Children's Research Hospital

URL

http://www.stjude.org/protocols

Description

Clinical Trials Open at St. Jude

Learn more about this trial

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

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