RetinoblastomaPhase 1NCT02792036
Intravitreal Carboplatin for the Treatment of Participants With Recurrent or Refractory Intraocular Retinoblastoma
A Phase 1 study testing Carboplatin, Maxitrol® and Focal Therapy in people with Retinoblastoma, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Retinoblastoma
- What is being tested?
- Carboplatin, Maxitrol® and Focal Therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2016to 4 Oct 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
About this study
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:
Read more
- 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.
Read the 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
- Being tested
- Carboplatin, Maxitrol®, Focal Therapy, Plaque Radiotherapy
- Medical subject headings
- Retinoblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarboplatinDrug
Also called Paraplatin®
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).
Maxitrol®Drug
Also called Anti-infective
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.
Focal TherapyProcedure or surgery
Also called Cryotherapy, Laser photocoagulation, Thermo-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.
Plaque RadiotherapyProcedure or surgery
Also called Brachytherapy
Participants who have developed progressive disease despite focal (non-irradiative) therapy will receive brachytherapy determined by consensus between the treating ophthalmologist and radiation oncologist.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Participants with retinoblastoma that is refractory or has relapsed inside the eye.
Interventions: Carboplatin, Maxitrol® , focal therapy, plaque radiotherapy. Receives: Drug: Carboplatin; Drug: Maxitrol®; Procedure: Focal Therapy; Procedure: Plaque Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From baseline through end of therapy (up to 5 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2016 (estimated)
- Study start1 Nov 2016
- Primary completion4 Oct 2019
- Study completion4 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for RetinoblastomaStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rachel Brennan, MD, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02792036
- Sponsor's protocol ID
- iRET
- Other IDs
- NCI-2016-00848
- Status last verified
- Feb 2020
- First submitted
- 2 Jun 2016
- Last updated
- 20 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intravitreal Carboplatin for the Treatment of Participants With Recurrent or Refractory Intraocular Retinoblastoma
- ClinicalTrials.gov ID
- NCT02792036
- Acronym / sponsor ID
- iRET
- Conditions
- Retinoblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Study start
- 1 Nov 2016 (actual)
- Primary completion
- 4 Oct 2019 (actual)
- Study completion
- 4 Oct 2019 (actual)
- First posted
- 7 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: Carboplatin, Drug: Maxitrol®, Procedure: Focal Therapy, Procedure: Plaque RadiotherapyParticipants with retinoblastoma that is refractory or has relapsed inside the eye. Interventions: Carboplatin, Maxitrol® , focal therapy, plaque radiotherapy. |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- Refractory or recurrent retinoblastoma with vitreous seeding meeting eligibility criteria by ultrasonic biomicroscopy performed during examination under anesthesia (EUA) by an ophthalmologist:
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarboplatinAlso: Paraplatin®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 | Treatment |
| Maxitrol®Also: Anti-infectiveMaxitrol® 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. | Drug | Treatment |
| Focal TherapyAlso: Cryotherapy, Laser photocoagulation, Thermo-therapySimultaneously 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 or surgery | Treatment |
| Plaque RadiotherapyAlso: BrachytherapyParticipants who have developed progressive disease despite focal (non-irradiative) therapy will receive brachytherapy determined by consensus between the treating ophthalmologist and radiation oncologist. | Procedure or surgery | Treatment |
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2020.
- St. Jude Children's Research HospitalLink provided by the sponsor.
- Clinical Trials Open at St. JudeLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rachel Brennan, MD principal investigator
St. Jude Children's Research Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Carboplatin, Maxitrol® and Focal Therapy in people with Retinoblastoma, run by St. Jude Children's Research Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants who develop dose-limiting toxicity (DLT) (time frame: From baseline through end of therapy (up to 5 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2020.