Intraocular RetinoblastomaPhase 3NCT00072384
Systemic Chemotherapy and Subtenon Carboplatin, and Local Ophthalmic Therapy in Children With Intraocular Retinoblastoma
A Phase 3 study testing liposomal vincristine sulfate, cryosurgery and laser surgery in people with Intraocular Retinoblastoma, run by Children's Oncology Group at 11 sites in United States.
Trial summary
Phase III trial to determine the effectiveness of combining systemic chemotherapy and subtenon carboplatin with ophthalmic therapy in treating children who have intraocular retinoblastoma. Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Intraocular Retinoblastoma
- What is being tested?
- liposomal vincristine sulfate, cryosurgery and laser surgery
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 11 sitesUnited States
- Study dates
- 16 Apr 2007to 30 Jun 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Diagnosis of bilateral retinoblastoma with at least 1 eye group C or D intraocular retinoblastoma by ophthalmologic examination, defined by the International Classification System for Intraocular Retinoblastoma as the following:
- Group C: Discrete localized disease with minimal subretinal and/or vitreous seeding
- Subretinal fluid, without prior or concurrent seeding, involving ≤ one quarter of the retina
- Local fine vitreous seeding may be present close to discrete tumor
- Local subretinal seeding < 3 mm from tumor
- Group D: Diffuse disease with significant vitreous and/or subretinal seeding
Show all 37Show fewer
- Tumor(s) may be massive or diffuse
- Subretinal fluid, without prior or concurrent seeding, involving up to total retinal detachment
- Diffuse or massive vitreous disease may include "greasy" seeds or avascular tumor masses
- Diffuse subretinal seeding may include subretinal plaques or tumor nodules
- Prior enucleation of 1 eye allowed provided the remaining eye is group C or D
- No tumor present on histologic examination at the cut end of the optic nerve on any eye enucleated prior to study entry
- Evidence of choroidal and/or optic nerve invasion past the lumina cribrosa is allowed
- No extraocular retinoblastoma clinically or by MRI of brain and orbits with and without gadolinium or CT scan with and without contrast of brain and orbits
- No evidence of systemic metastases by bone marrow, lumbar puncture, bone scan, and/or any other additional test
- Performance status - Karnofsky 50-100% (over 16 years of age)
- Performance status - Lansky 50-100% (16 and under)
- Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
- AST and ALT < 2.5 times ULN for age
- Creatinine adjusted according to age as follows:
- No greater than 0.4 mg/dL (≤ 5 months)
- No greater than 0.5 mg/dL (6 months -11 months)
- No greater than 0.6 mg/dL (1 year-23 months)
- No greater than 0.8 mg/dL (2 years-5 years)
- No greater than 1.0 mg/dL (6 years-9 years)
- No greater than 1.2 mg/dL (10 years-12 years)
- No greater than 1.4 mg/dL (13 years and over [female])
- No greater than 1.5 mg/dL (13 years to 15 years [male])
- No greater than 1.7 mg/dL (16 years and over [male])
- Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min/1.73m^2
- Not pregnant or nursing
- Fertile patients must use effective contraception
- Negative pregnancy test in postmenarchal females
- No prior chemotherapy
- No other concurrent chemotherapy
- No prior radiotherapy
- No other concurrent radiotherapy
Who cannot join
None listed.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Children's Oncology Group
Arcadia, California, 91006-3776
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322
University of Illinois
Chicago, Illinois, 60612
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Southern California Permanente Medical Group
Downey, California, 90242
Duke University Medical Center
Durham, North Carolina, 27710
Baylor College of Medicine
Houston, Texas, 77030
M D Anderson Cancer Center
Houston, Texas, 77030
Children's Hospital Los Angeles
Los Angeles, California, 90027
Yale University
New Haven, Connecticut, 06520-8032
Lombardi Comprehensive Cancer Center at Georgetown University
Washington D.C., District of Columbia, 20057
About this study
Official title: A Single Arm Trial of Systemic And Subtenon Chemotherapy For Groups C And D Intraocular Retinoblastoma
Phase III trial to determine the effectiveness of combining systemic chemotherapy and subtenon carboplatin with ophthalmic therapy in treating children who have intraocular retinoblastoma. Drugs used in chemotherapy, such as vincristine, carboplatin, and etoposide, work in different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether systemic chemotherapy and subtenon (under the conjunctiva of the eye) carboplatin combined with ophthalmic therapy is effective in treating intraocular (within the eyeball) retinoblastoma.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the event-free survival at 12 months of pediatric patients' eyes with group D intraocular retinoblastoma treated with systemic chemotherapy comprising vincristine, carboplatin, and etoposide, subtenon carboplatin, and local ophthalmic therapy. (Event defined for each eye individually as needed for nonprotocol therapy including nonprotocol chemotherapy, enucleation or any external-beam radiation)
SECONDARY OBJECTIVES:
- Determine the event-free survival at 12 months of pediatric patients' eyes with group C retinoblastoma treated with systemic chemotherapy comprising carboplatin, etoposide, vincristine, subtenon carboplatin, and local ophthalmic therapy.
II. Determine the acute and long-term toxic effects of these regimens in these patients, including visual outcome and incidence of secondary malignancies.
III. Determine the patterns of failure in patients treated with these regimens, in terms of vitreous vs retinal vs both as sites of recurrence.
IV. Determine predictors of failure including findings at the on study examination under anesthesia and response status after six courses of chemotherapy.
- Determine the percentage of group C and D eyes separately that can be preserved without enucleation after failing protocol therapy.
OUTLINE: This is a multicenter study.
Patients receive vincristine IV over 1 minute on day 1 and carboplatin IV over 1 hour and etoposide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 3 and continuing until blood counts recover. Patients receive subtenon carboplatin to each group C or D eye on day 0 or 1 prior of courses 2-4 only. Treatment repeats every 28 days for 6 courses in the absence of occurrence of extraocular retinoblastoma or a second malignancy. Beginning with course 3 of systemic chemotherapy, patients undergo local ophthalmic therapy comprising local laser and/or cryotherapy on day 1.
Patients are followed with ophthalmology exams every 4-12 weeks until 3 years of age, every 6 months until 5 years of age, and then annually for up to 10 years.
- Conditions
- Intraocular Retinoblastoma
- Being tested
- liposomal vincristine sulfate, cryosurgery, laser surgery, carboplatin, etoposide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
liposomal vincristine sulfateDrug
Also called liposomal vincristine, Marqibo, vincristine liposomal, vincristine sulfate liposome injection
Given IV
cryosurgeryProcedure or surgery
Also called cryoablation, cryosurgical ablation
Application of extreme cold to destroy abnormal or diseased tissue.
laser surgeryProcedure or surgery
Also called conventional laser therapy, laser therapy, conventional, surgery, laser
Surgery using a laser (instead of a scalpel) to cut tissue
carboplatinDrug
Also called Carboplat, CBDCA, JM-8, Paraplat
Given IV
etoposideDrug
Also called EPEG, VP-16, VP-16-213
Given IV
filgrastimBiological
Also called G-CSF, Neupogen
Given subcutaneously
| Study group | Role | What they receive |
|---|---|---|
| Treatment (chemotherapy, surgery) | Experimental | Patients receive liposomal vincristine sulfate IV over 1 minute on day 1 and carboplatin IV over 1 hour and etoposide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 3 and continuing until blood counts recover. Patients receive subtenon carboplatin to each group C or D eye on day 0 or 1prior of courses 2-4 only. Treatment repeats every 28 days for 6 courses in the absence of occurrence of extraocular retinoblastoma or a second malignancy. Beginning with course 3 of systemic chemotherapy, patients undergo local ophthalmic therapy comprising local laser surgery and/or cryosurgery on day 1. Receives: Drug: liposomal vincristine sulfate; Procedure: cryosurgery; Procedure: laser surgery; Drug: carboplatin; Drug: etoposide; Biological: filgrastim |
What is being measured
The primary outcome is the main question the study is designed to answer.
Group D Eyes - Treatment Failure Within One Year
Each Group D eye will be classified as experiencing failure within one year after start of treatment: yes or no. The method of Rosner et al. (Biometrics v. 38, 105-114, 1982) will be used to model possible dependence between eyes from the same patient. The point estimate of the probability of treatment failure is reported as the "Mean" measure type.
Measured: One year
Group C Eyes - Treatment Failure Within One Year
Each Group C eye will be classified as experiencing failure within one year after start of treatment: yes or no. The method of Rosner et al. (Biometrics v. 38, 105-114, 1982) will be used to model possible dependence between eyes from the same patient. The point estimate of the probability of treatment failure is reported as the "Mean" measure type.
Measured: One year
Secondary outcomes (4)
Event-free Survival (EFS)
Proportion of patients event free at 1 year following enrollment. Event free survival time is computed as the time to study entry until disease relapse/progression, secondary malignancy, or death.
Measured: One year after study enrollment
Toxicity Associated With Chemotherapy
The number of patients that experience CTC Version 4 grade 3 or higher toxicities of any kind.
Measured: From date of enrollment until termination of protocol therapy assessed up to 72 weeks
Patterns of Failure for Group C and Group D in Terms of Vitreous vs Patterns of Failure for Group C and Group D in Terms of Vitreous vs Retinal vs Both as Sites of Recurrence
Sites of disease recurrence for Group C and Group D eyes where treatment failure was detected
Measured: From the date of enrollment assessed up to 36 months
Patterns of Treatment Failure vs. no Treatment Failure for Group C Eyes and Group D Eyes According to Initial Sites of Involvement
The association between the probability of experiencing treatment failure vs. no failure in a C eye and the presence of subretinal seeding (SRS), subretinal fluid (SRF), or vitreal seeding (VS) at the on study ophthalmological examination under anesthesia. The association between the probability of experiencing treatment failure vs. no failure in a D eye and the presence of subretinal seeding (SRS), subretinal fluid (SRF), or vitreal seeding (VS) at the on study ophthalmological examination under anesthesia.
Measured: From the date of enrollment assessed up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2003 (estimated)
- Study start16 Apr 2007
- Primary completion1 Feb 2013
- Study completion30 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Intraocular RetinoblastomaStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Rima Jubran, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00072384
- Sponsor's protocol ID
- ARET0231
- Other IDs
- NCI-2009-00420, CDR0000339627, COG-ARET0231, U10CA098543
- Status last verified
- Jul 2021
- First submitted
- 4 Nov 2003
- Last updated
- 30 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm Trial of Systemic And Subtenon Chemotherapy For Groups C And D Intraocular Retinoblastoma
- ClinicalTrials.gov ID
- NCT00072384
- Acronym / sponsor ID
- ARET0231
- Conditions
- Intraocular Retinoblastoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 16 Apr 2007 (actual)
- Primary completion
- 1 Feb 2013 (actual)
- Study completion
- 30 Jun 2021 (actual)
- First posted
- 6 Nov 2003 (estimated)
- Results
- Posted 19 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase III trial to determine the effectiveness of combining systemic chemotherapy and subtenon carboplatin with ophthalmic therapy in treating children who have intraocular retinoblastoma. Drugs used in chemotherapy, such as vincristine, carboplatin, and etoposide, work in different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether systemic chemotherapy and subtenon (under the conjunctiva of the eye) carboplatin combined with ophthalmic therapy is effective in treating intraocular (within the eyeball) retinoblastoma.
Detailed description
PRIMARY OBJECTIVES:
- Determine the event-free survival at 12 months of pediatric patients' eyes with group D intraocular retinoblastoma treated with systemic chemotherapy comprising vincristine, carboplatin, and etoposide, subtenon carboplatin, and local ophthalmic therapy. (Event defined for each eye individually as needed for nonprotocol therapy including nonprotocol chemotherapy, enucleation or any external-beam radiation)
SECONDARY OBJECTIVES:
- Determine the event-free survival at 12 months of pediatric patients' eyes with group C retinoblastoma treated with systemic chemotherapy comprising carboplatin, etoposide, vincristine, subtenon carboplatin, and local ophthalmic therapy.
II. Determine the acute and long-term toxic effects of these regimens in these patients, including visual outcome and incidence of secondary malignancies.
III. Determine the patterns of failure in patients treated with these regimens, in terms of vitreous vs retinal vs both as sites of recurrence.
IV. Determine predictors of failure including findings at the on study examination under anesthesia and response status after six courses of chemotherapy.
- Determine the percentage of group C and D eyes separately that can be preserved without enucleation after failing protocol therapy.
OUTLINE: This is a multicenter study.
Patients receive vincristine IV over 1 minute on day 1 and carboplatin IV over 1 hour and etoposide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 3 and continuing until blood counts recover. Patients receive subtenon carboplatin to each group C or D eye on day 0 or 1 prior of courses 2-4 only. Treatment repeats every 28 days for 6 courses in the absence of occurrence of extraocular retinoblastoma or a second malignancy. Beginning with course 3 of systemic chemotherapy, patients undergo local ophthalmic therapy comprising local laser and/or cryotherapy on day 1.
Patients are followed with ophthalmology exams every 4-12 weeks until 3 years of age, every 6 months until 5 years of age, and then annually for up to 10 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (chemotherapy, surgery) | Experimental | Drug: liposomal vincristine sulfate, Procedure: cryosurgery, Procedure: laser surgery, Drug: carboplatin, Drug: etoposide, Biological: filgrastimPatients receive liposomal vincristine sulfate IV over 1 minute on day 1 and carboplatin IV over 1 hour and etoposide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 3 and continuing until blood counts recover. Patients receive subtenon carboplatin to each group C or D eye on day 0 or 1prior of courses 2-4 only. Treatment repeats every 28 days for 6 courses in the absence of occurrence of extraocular retinoblastoma or a second malignancy. Beginning with course 3 of systemic chemotherapy, patients undergo local ophthalmic therapy comprising local laser surgery and/or cryosurgery on day 1. |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (37 listed)
- Diagnosis of bilateral retinoblastoma with at least 1 eye group C or D intraocular retinoblastoma by ophthalmologic examination, defined by the International Classification System for Intraocular Retinoblastoma as the following:
- Prior enucleation of 1 eye allowed provided the remaining eye is group C or D
- No tumor present on histologic examination at the cut end of the optic nerve on any eye enucleated prior to study entry
- No extraocular retinoblastoma clinically or by MRI of brain and orbits with and without gadolinium or CT scan with and without contrast of brain and orbits
- No evidence of systemic metastases by bone marrow, lumbar puncture, bone scan, and/or any other additional test
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| liposomal vincristine sulfateAlso: liposomal vincristine, Marqibo, vincristine liposomal, vincristine sulfate liposome injectionGiven IV | Drug | Treatment (chemotherapy, surgery) |
| cryosurgeryAlso: cryoablation, cryosurgical ablationApplication of extreme cold to destroy abnormal or diseased tissue. | Procedure or surgery | Treatment (chemotherapy, surgery) |
| laser surgeryAlso: conventional laser therapy, laser therapy, conventional, surgery, laserSurgery using a laser (instead of a scalpel) to cut tissue | Procedure or surgery | Treatment (chemotherapy, surgery) |
| carboplatinAlso: Carboplat, CBDCA, JM-8, ParaplatGiven IV | Drug | Treatment (chemotherapy, surgery) |
| etoposideAlso: EPEG, VP-16, VP-16-213Given IV | Drug | Treatment (chemotherapy, surgery) |
| filgrastimAlso: G-CSF, NeupogenGiven subcutaneously | Biological | Treatment (chemotherapy, surgery) |
Primary outcome
Group D Eyes - Treatment Failure Within One Year
Time frame: One year
Each Group D eye will be classified as experiencing failure within one year after start of treatment: yes or no. The method of Rosner et al. (Biometrics v. 38, 105-114, 1982) will be used to model possible dependence between eyes from the same patient. The point estimate of the probability of treatment failure is reported as the "Mean" measure type.
Group C Eyes - Treatment Failure Within One Year
Time frame: One year
Each Group C eye will be classified as experiencing failure within one year after start of treatment: yes or no. The method of Rosner et al. (Biometrics v. 38, 105-114, 1982) will be used to model possible dependence between eyes from the same patient. The point estimate of the probability of treatment failure is reported as the "Mean" measure type.
4 secondary outcomes
Event-free Survival (EFS)
Time frame: One year after study enrollment
Toxicity Associated With Chemotherapy
Time frame: From date of enrollment until termination of protocol therapy assessed up to 72 weeks
Patterns of Failure for Group C and Group D in Terms of Vitreous vs Patterns of Failure for Group C and Group D in Terms of Vitreous vs Retinal vs Both as Sites of Recurrence
Time frame: From the date of enrollment assessed up to 36 months
Patterns of Treatment Failure vs. no Treatment Failure for Group C Eyes and Group D Eyes According to Initial Sites of Involvement
Time frame: From the date of enrollment assessed up to 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Rima Jubran principal investigator
Children's Oncology Group
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing liposomal vincristine sulfate, cryosurgery and laser surgery in people with Intraocular Retinoblastoma, run by Children's Oncology Group at 11 sites 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 37 inclusion and 0 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 30 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Group D Eyes - Treatment Failure Within One Year (time frame: One year). The study lists 2 primary outcomes in all. 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 30 Jul 2021.