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

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ClinicalTrials.gov Identifier: NCT02792036
Recruitment Status : Recruiting
First Posted : June 7, 2016
Last Update Posted : December 2, 2017
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

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.

Condition or disease Intervention/treatment Phase
Retinoblastoma Drug: Carboplatin Drug: Maxitrol® Procedure: Focal Therapy Procedure: Plaque Radiotherapy Phase 1

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 Aqueous fluid (0.1-0.15ml) will be withdrawn and sent for pathology review.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  (Clinical Trial)
Estimated Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Intravitreal Carboplatin for the Treatment of Participants With Recurrent or Refractory Intraocular Retinoblastoma
Actual Study Start Date : November 1, 2016
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2024

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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:
  • Cryotherapy
  • Laser photocoagulation
  • 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 Name: Brachytherapy




Primary Outcome Measures :
  1. Number of participants who develop dose-limiting toxicity (DLT) [ Time Frame: From baseline through end of therapy (up to 5 months) ]

    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.




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Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02792036


Contacts
Contact: Rachel Brennan, MD 866-278-5833 referralinfo@stjude.org

Locations
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Rachel C. Brennan, MD    866-278-5833    referralinfo@stjude.org   
Principal Investigator: Rachel C. Brennan, MD         
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Principal Investigator: Rachel Brennan, MD St. Jude Children's Research Hospital

Additional Information:
Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT02792036     History of Changes
Other Study ID Numbers: iRET
NCI-2016-00848 ( Registry Identifier: NCI Clinical Trial Registration Program )
First Posted: June 7, 2016    Key Record Dates
Last Update Posted: December 2, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Retinoblastoma
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
Retinal Diseases
Carboplatin
Dexamethasone, neomycin, polymyxin B drug combination
Antineoplastic Agents
Anti-Bacterial Agents
Anti-Infective Agents