Intraocular RetinoblastomaPhase 3NCT00079417
Neoadjuvant Carboplatin and Vincristine and Standard Local Ophthalmic Therapy in Treating Patients With Intraocular Retinoblastoma
A Phase 3 study testing Carboplatin, Cryosurgery and Infrared Laser Therapy in people with Intraocular Retinoblastoma, run by Children's Oncology Group at 10 sites in United States.
Trial summary
This phase III trial is studying how well giving carboplatin and vincristine together with standard local ophthalmic therapy works in treating children with intraocular retinoblastoma. Read more about this study
- Who is it for?
- Ages Up to 5 years
- Conditions the study is for
- Intraocular Retinoblastoma
- What is being tested?
- Carboplatin, Cryosurgery and Infrared Laser Therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 10 sitesUnited States
- Study dates
- 26 Dec 2005to 31 Mar 2017
- 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 5 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Newly diagnosed Group B intraocular retinoblastoma meeting 1 of the following criteria:
- Group B tumor(s) in 1 eye
- Group B tumor(s) in both eyes
- Group A tumor in 1 eye and Group B tumor(s) in the other eye
- Group E tumor in 1 eye that has been enucleated and Group B tumor(s) in the remaining eye at the time of enucleation of the Group E tumor
- Defined by the International Classification System for Intraocular Retinoblastoma as follows:
Show all 37Show fewer
- Group A: Small tumors (≤ 3 mm in greatest dimension) confined to the retina, away from foveola and disc meeting the following criteria:
- More than 3 mm from fovea
- More than 1.5 mm from optic disk
- Group B: Tumors more than 3 mm meeting the following criteria:
- Confined to the retina in any location not in Group A
- Tumor associated subretinal fluid < 3 mm from the tumor margin with no subretinal seeding
- Group E: Must have ≥ 1 of the following present:
- Tumor touching the lens
- Tumor anterior to anterior vitreous face involving ciliary body or anterior segment
- Diffuse infiltrating retinoblastoma
- Neovascular glaucoma
- Opaque media from hemorrhage
- Tumor necrosis with aseptic orbital cellulites
- Phthisis bulbi
- Confirmation of diagnosis by CT scan or MRI of the brain and orbits AND an ophthalmologic evaluation under anesthesia within the past 3 weeks
- No choroidal and/or optic nerve invasion past the lamina cribosa
- No evidence of extraocular retinoblastoma clinically or by head and orbital MRI and/or CT scan
- No tumor present on histological exam at the cut end of the optic nerve for any Group E eye enucleated before study entry
- Performance status - ECOG 0-2
- Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
- AST or ALT < 2.5 times ULN for age
- Creatinine clearance (based on Schwartz formula) or radioisotope glomerular filtration rate ≥ 70mL/min/1.73 m^2
- No prior chemotherapy
- No other concurrent chemotherapy
- No prior radiotherapy
- No other concurrent radiotherapy, including intensity-modulated stereotactic, or proton beam radiotherapy
- Prior enucleation of one eye allowed provided the remaining eye is Group B
- No concurrent enucleation
- No prior local ophthalmic therapy for retinoblastoma
- No other prior therapy for retinoblastoma
- No local therapy during chemotherapy course 1
Who cannot join
None listed.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
Duke University Medical Center
Durham, North Carolina, 27710
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
Children's Hospital Los Angeles
Los Angeles, California, 90027
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Oncology Group
Philadelphia, Pennsylvania, 19104
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
About this study
Official title: Trial of Systemic Neoadjuvant Chemotherapy for Group B Intraocular Retinoblastoma
This phase III trial is studying how well giving carboplatin and vincristine together with standard local ophthalmic therapy works in treating children with intraocular retinoblastoma. Drugs used in chemotherapy, such as carboplatin and vincristine, work in different ways to stop tumor from dividing so they stop growing or die. It is not yet known whether neoadjuvant chemotherapy combined with standard local ophthalmic therapy is effective in treating intraocular retinoblastoma.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the 2-year event-free survival of patients with Group B intraocular retinoblastoma treated with neoadjuvant chemoreduction comprising carboplatin and vincristine and standardized local ophthalmic therapy.
SECONDARY OBJECTIVES:
- Determine the response rate after one course of chemoreduction (before standardized local ophthalmic therapy) in these patients.
II. Correlate response rate with event-free survival in patients treated with this regimen.
III. Determine the incidence of toxic effects in patients treated with this regimen.
OUTLINE: This is a multicenter study.
Patients receive chemoreduction comprising carboplatin IV over 60 minutes followed by vincristine IV over 1-2 minutes on day 1. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. After the first course of chemoreduction, patients undergo standardized local ophthalmic therapy comprising local laser therapy, cryotherapy, and/or radioactive plaque comprising iodine I 125 or ruthenium Ru 106.
Patients are followed every 3-4 weeks until there is no active tumor seen on a minimum of 3 ophthalmic exams under anesthesia, every 6-8 weeks until 3 years of age, every 4-6 months until 10 years of age, and then annually thereafter.
- Conditions
- Intraocular Retinoblastoma
- Being tested
- Carboplatin, Cryosurgery, Infrared Laser Therapy, Iodine I-125, Radiation Therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarboplatinDrug
Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino
Given IV
CryosurgeryProcedure or surgery
Also called Ablation, Cryo, Cryoablation, cryosurgical ablation
Infrared Laser TherapyProcedure or surgery
Iodine I-125Radiation
Also called 125-Iodine, I-125, Iodine 125, Iodine I 125
Undergo radioactive therapy
Radiation TherapyRadiation
Also called Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated
Undergo radioactive therapy
Ruthenium Ru-106Radiation
Also called Ru-106, Ruthenium Ru 106
Undergo radioactive therapy
Also called Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (chemotherapy, surgery) | Experimental | Patients receive chemoreduction comprising carboplatin IV over 60 minutes followed by vincristine IV over 1-2 minutes on day 1. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. After the first course of chemoreduction, patients undergo standardized local ophthalmic therapy comprising local laser therapy, cryotherapy, and/or radioactive plaque comprising iodine I 125 or ruthenium Ru 106. Receives: Drug: Carboplatin; Procedure: Cryosurgery; Procedure: Infrared Laser Therapy; Radiation: Iodine I-125; Radiation: Radiation Therapy; Radiation: Ruthenium Ru-106; Drug: Vincristine Sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free Survival
Proportion of patients with event free survival at 2 years. An event is defined as the need for non-protocol therapy, defined as additional on-protocol chemotherapy, enucleation or external beam radiation, among patients with Group B intraocular tumors with a schedule of neoadjuvant 2-agent (Vincristine/Carboplatin) chemotherapy (chemo-reduction) and standardized local ophthalmic therapy.
Measured: At 2 years
Secondary outcomes (4)
Response Rate (RR) at Patient Level After the First Course of Therapy
RR will be estimated. The response after 1 course of chemotherapy will be used to better define response to this neoadjuvant systemic chemotherapy, prior to the use of local ophthalmic therapy. Response to subsequent courses will help define response to combined systemic chemotherapy and local ophthalmic therapy. Number of patients with Type I, II, III or IV response after first course of therapy
Measured: 1 month after enrollment
Response Rate (RR) at Eye Levels After the First Course of Therapy
RR will be estimated. The response after 1 course of chemotherapy will be used to better define response to this neoadjuvant systemic chemotherapy, prior to the use of local ophthalmic therapy. Response to subsequent courses will help define response to combined systemic chemotherapy and local ophthalmic therapy. Number eyes with Type I, II, III or IV response after first course of therapy
Measured: 1 month after enrollment
Event-free Survival Rate (EFSR) Defined as the Need for Non-protocol Chemotherapy, Enucleation, or EBRT at the Patient Level
EFSR will be estimated for patients who respond to vincristine and carboplatin after an initial 1 cycle of chemoreduction
Measured: 2 years after enrollment
Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0
Participants with Grade 3 and higher reported on protocol therapy
Measured: 6 months after enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2004 (estimated)
- Study start26 Dec 2005
- Primary completion1 Jan 2010
- Study completion31 Mar 2017
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
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Debra L Friedman, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00079417
- Sponsor's protocol ID
- ARET0331
- Other IDs
- NCI-2009-00422, ARET0331, CDR0000355721, COG-ARET0331, ARET0331, ARET0331, U10CA098543
- Status last verified
- Jan 2023
- First submitted
- 8 Mar 2004
- Last updated
- 13 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Trial of Systemic Neoadjuvant Chemotherapy for Group B Intraocular Retinoblastoma
- ClinicalTrials.gov ID
- NCT00079417
- Acronym / sponsor ID
- ARET0331
- Conditions
- Intraocular Retinoblastoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 26 Dec 2005 (actual)
- Primary completion
- 1 Jan 2010 (actual)
- Study completion
- 31 Mar 2017 (actual)
- First posted
- 10 Mar 2004 (estimated)
- Results
- Posted 14 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase III trial is studying how well giving carboplatin and vincristine together with standard local ophthalmic therapy works in treating children with intraocular retinoblastoma. Drugs used in chemotherapy, such as carboplatin and vincristine, work in different ways to stop tumor from dividing so they stop growing or die. It is not yet known whether neoadjuvant chemotherapy combined with standard local ophthalmic therapy is effective in treating intraocular retinoblastoma.
Detailed description
PRIMARY OBJECTIVES:
- Determine the 2-year event-free survival of patients with Group B intraocular retinoblastoma treated with neoadjuvant chemoreduction comprising carboplatin and vincristine and standardized local ophthalmic therapy.
SECONDARY OBJECTIVES:
- Determine the response rate after one course of chemoreduction (before standardized local ophthalmic therapy) in these patients.
II. Correlate response rate with event-free survival in patients treated with this regimen.
III. Determine the incidence of toxic effects in patients treated with this regimen.
OUTLINE: This is a multicenter study.
Patients receive chemoreduction comprising carboplatin IV over 60 minutes followed by vincristine IV over 1-2 minutes on day 1. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. After the first course of chemoreduction, patients undergo standardized local ophthalmic therapy comprising local laser therapy, cryotherapy, and/or radioactive plaque comprising iodine I 125 or ruthenium Ru 106.
Patients are followed every 3-4 weeks until there is no active tumor seen on a minimum of 3 ophthalmic exams under anesthesia, every 6-8 weeks until 3 years of age, every 4-6 months until 10 years of age, and then annually thereafter.
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: Carboplatin, Procedure: Cryosurgery, Procedure: Infrared Laser Therapy, Radiation: Iodine I-125, Radiation: Radiation Therapy, Radiation: Ruthenium Ru-106, Drug: Vincristine SulfatePatients receive chemoreduction comprising carboplatin IV over 60 minutes followed by vincristine IV over 1-2 minutes on day 1. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. After the first course of chemoreduction, patients undergo standardized local ophthalmic therapy comprising local laser therapy, cryotherapy, and/or radioactive plaque comprising iodine I 125 or ruthenium Ru 106. |
Who may qualify
- Ages
- Up to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (37 listed)
- Newly diagnosed Group B intraocular retinoblastoma meeting 1 of the following criteria:
- Defined by the International Classification System for Intraocular Retinoblastoma as follows:
- Confirmation of diagnosis by CT scan or MRI of the brain and orbits AND an ophthalmologic evaluation under anesthesia within the past 3 weeks
- No choroidal and/or optic nerve invasion past the lamina cribosa
- No evidence of extraocular retinoblastoma clinically or by head and orbital MRI and/or CT scan
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 |
|---|---|---|
| CarboplatinAlso: Blastocarb, Carboplat, Carboplatin Hexal, CarboplatinoGiven IV | Drug | Treatment (chemotherapy, surgery) |
| CryosurgeryAlso: Ablation, Cryo, Cryoablation, cryosurgical ablation | Procedure or surgery | Treatment (chemotherapy, surgery) |
| Infrared Laser Therapy | Procedure or surgery | Treatment (chemotherapy, surgery) |
| Iodine I-125Also: 125-Iodine, I-125, Iodine 125, Iodine I 125Undergo radioactive therapy | Radiation | Treatment (chemotherapy, surgery) |
| Radiation TherapyAlso: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, IrradiatedUndergo radioactive therapy | Radiation | Treatment (chemotherapy, surgery) |
| Ruthenium Ru-106Also: Ru-106, Ruthenium Ru 106Undergo radioactive therapy | Radiation | Treatment (chemotherapy, surgery) |
| Vincristine SulfateAlso: Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, OncovinGiven IV | Drug | Treatment (chemotherapy, surgery) |
Primary outcome
Event-free Survival
Time frame: At 2 years
Proportion of patients with event free survival at 2 years. An event is defined as the need for non-protocol therapy, defined as additional on-protocol chemotherapy, enucleation or external beam radiation, among patients with Group B intraocular tumors with a schedule of neoadjuvant 2-agent (Vincristine/Carboplatin) chemotherapy (chemo-reduction) and standardized local ophthalmic therapy.
4 secondary outcomes
Response Rate (RR) at Patient Level After the First Course of Therapy
Time frame: 1 month after enrollment
Response Rate (RR) at Eye Levels After the First Course of Therapy
Time frame: 1 month after enrollment
Event-free Survival Rate (EFSR) Defined as the Need for Non-protocol Chemotherapy, Enucleation, or EBRT at the Patient Level
Time frame: 2 years after enrollment
Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0
Time frame: 6 months after enrollment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2023.
- 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.
Debra L Friedman principal investigator
Children's Oncology Group
10 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 Carboplatin, Cryosurgery and Infrared Laser Therapy in people with Intraocular Retinoblastoma, run by Children's Oncology Group at 10 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 13 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 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 14 Feb 2014). 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?
Event-free Survival (time frame: At 2 years). 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 13 Mar 2023.