Intraocular RetinoblastomaPhase 3NCT00335738
Vincristine, Carboplatin, and Etoposide or Observation Only in Treating Patients Who Have Undergone Surgery for Newly Diagnosed Retinoblastoma
A Phase 3 study testing liposomal vincristine sulfate, carboplatin and etoposide in people with Intraocular Retinoblastoma, run by Children's Oncology Group at 56 sites in 5 countries.
Trial summary
This phase III trial is studying vincristine, carboplatin, and etoposide to see how well they work compared to observation only in treating patients who have undergone surgery for newly diagnosed retinoblastoma. Read more about this study
- Who is it for?
- Ages Up to 6 years
- Conditions the study is for
- Intraocular Retinoblastoma
- What is being tested?
- liposomal vincristine sulfate, carboplatin and etoposide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 331 participants
- Where
- 56 sitesin 5 countries
- Study dates
- Dec 2005to 30 Sep 2020
- 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 6 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Newly diagnosed unilateral retinoblastoma
- Underwent enucleation as primary therapy within the past 5 weeks
- Must enroll and submit pathology slides within 21 days of enucleation
- Adjuvant chemotherapy must begin within 35 days after enucleation
- Disease with or without high-risk histopathologic features
- High-risk features are defined as any of the following:
Show all 35Show fewer
- Posterior uveal invasion (includes choroidal invasion)
- Any degree of concomitant choroid and/or optic nerve involvement
- Tumor involving the optic nerve posterior to the lamina cribrosa as an independent finding
- Scleral invasion
- Anterior chamber seeding
- Ciliary body infiltration
- Iris infiltration
- No evidence of extraocular retinoblastoma clinically, by CT scan, or by MRI of the brain and orbits with and without gadolinium
- No tumor at the cut end of the optic nerve on any eye enucleated as evidenced by histologic examination prior to study entry
- No systemic metastases as evidenced by bone marrow scan, bone scan, or any other additional test at study entry
- Lansky performance status 50-100%
- Hemoglobin > 8 g/dL
- Absolute neutrophil count ≥ 1,000/mm³
- Platelet count ≥ 100,000/mm³
- 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
- Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
- AST or ALT < 2.5 times ULN for age
- No prior therapy other than enucleation
- No prior chemotherapy
Who cannot join
None listed.
Trial locations and contacts
56 sites in 5 countries.
56 sites in 5 countries
United States48 sites
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
Children's Oncology Group
Arcadia, California, 91006-3776
Children's Hospital Colorado
Aurora, Colorado, 80045
Johns Hopkins University
Baltimore, Maryland, 21287-8936
Lehigh Valley Hospital - Muhlenberg
Bethlehem, Pennsylvania, 18017
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Brooklyn Hospital Center
Brooklyn, New York, 11201
Carolinas Medical Center
Charlotte, North Carolina, 28203
University of Illinois
Chicago, Illinois, 60612
Childrens Memorial Hospital
Chicago, Illinois, 60614
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Nationwide Children's Hospital
Columbus, Ohio, 43205
The Children's Medical Center of Dayton
Dayton, Ohio, 45404
Wayne State University
Detroit, Michigan, 48202
Southern California Permanente Medical Group
Downey, California, 90242
Duke University Medical Center
Durham, North Carolina, 27710
Cook Children's Medical Center
Fort Worth, Texas, 76104
Baylor College of Medicine
Houston, Texas, 77030
M D Anderson Cancer Center
Houston, Texas, 77030
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
The Childrens Mercy Hospital
Kansas City, Missouri, 64108
University of Kentucky
Lexington, Kentucky, 40536
Children's Hospital Los Angeles
Los Angeles, California, 90027
Kosair Children's Hospital
Louisville, Kentucky, 40202
Covenant Children's Hospital
Lubbock, Texas, 79410
Marshfield Clinic
Marshfield, Wisconsin, 54449
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Midwest Children's Cancer Center
Milwaukee, Wisconsin, 53226
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, 55455
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
Childrens Hospital-King's Daughters
Norfolk, Virginia, 23507
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Mayo Clinic
Rochester, Minnesota, 55905
Primary Children's Medical Center
Salt Lake City, Utah, 84113
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229-3900
Rady Children's Hospital - San Diego
San Diego, California, 92123
University of California San Francisco Medical Center-Parnassus
San Francisco, California, 94143
Maine Children's Cancer Program
Scarborough, Maine, 04074
Washington University School of Medicine
St Louis, Missouri, 63110
Scott and White Memorial Hospital
Temple, Texas, 76508
University of Arizona Health Sciences Center
Tucson, Arizona, 85724
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Lombardi Comprehensive Cancer Center at Georgetown University
Washington D.C., District of Columbia, 20057
Australia3 sites
Royal Brisbane and Women's Hospital
Herston, Queensland, 4029
Royal Children's Hospital
Parkville, Victoria, 3052
Princess Margaret Hospital for Children
Perth, Western Australia, 6008
Canada2 sites
Hospital Sainte-Justine
Montreal, Quebec, H3T 1C5
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9
New Zealand2 sites
Christchurch Hospital
Christchurch, 8011
Starship Children's Hospital
Grafton, Auckland, 1145
About this study
Official title: A Study of Unilateral Retinoblastoma With and Without Histopathologic High-Risk Features and the Role of Adjuvant Chemotherapy
This phase III trial is studying vincristine, carboplatin, and etoposide to see how well they work compared to observation only in treating patients who have undergone surgery for newly diagnosed retinoblastoma. Drugs used in chemotherapy, such as vincristine, carboplatin, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) after surgery may kill any tumor cells that remain after surgery. Sometimes, after surgery, no additional treatment is needed for the tumor until it progresses. In this case, observation may be sufficient.
Read the detailed description
OBJECTIVES:
- Prospectively determine the prevalence of high-risk histopathologic features, such as choroidal involvement, optic nerve invasion, and scleral and anterior segment involvement, in patients with newly diagnosed unilateral retinoblastoma who have undergone enucleation.
II. Demonstrate that patients without certain high-risk features can be successfully treated with enucleation alone by estimating the event-free survival (EFS) (where an event is defined as the occurrence of extraocular or metastatic disease) and overall survival (OS).
III. Estimate the EFS and OS of patients with specific high-risk features who are uniformly treated with adjuvant chemotherapy comprising vincristine, carboplatin, and etoposide.
IV. Estimate the incidence of toxicities associated with the proposed adjuvant chemotherapy regimen.
OUTLINE: This is a prospective, nonrandomized, multicenter study. Patients are assigned to 1 of 2 groups according to presence of high-risk histopathologic features.
GROUP 1 (high-risk features): Patients receive vincristine IV and carboplatin IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
GROUP 2 (no high-risk features): Patients undergo observation periodically for at least 5 years.
GROUP 3 (no consensus regarding high risk features can be reached): Patients undergo Group 1 chemotherapy or observation according to institutional high-risk feature assessment.
After completion of study treatment, patients in group 1 are followed periodically for at least 5 years.
- Conditions
- Intraocular Retinoblastoma
- Being tested
- liposomal vincristine sulfate, 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
carboplatinDrug
Also called Carboplat, CBDCA, JM-8, Paraplat
Given IV
etoposideDrug
Also called EPEG, VP-16, VP-16-213
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Group 1 (identified by central review as high risk) | Experimental | Includes patients who may or may not require chemotherapy. Patients who require chemotherapy receive vincristine IV and carboplatin IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity and patients who complete chemotherapy are followed after completion of therapy periodically for at least 5 years. Patients who do not require chemotherapy undergo observation periodically for at least 5 years. Receives: Drug: liposomal vincristine sulfate; Drug: carboplatin; Drug: etoposide |
| Group 2 (identified by central review as not high risk) | No intervention | Patients undergo observation periodically for at least 5 years. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free Survival (EFS)
EFS distributions will be estimated by the Kaplan-Meier method for patients with high risk features according to central review and treated with adjuvant chemotherapy and separately for subjects with central review recommendation of enucleation alone.
Measured: At 2 years
Overall Survival (OS)
OS distributions will be estimated by the Kaplan-Meier method for patients with high risk features according to central review and treated with adjuvant chemotherapy and separately for subjects with central review recommendation of enucleation alone.
Measured: At 2 Years
Secondary outcomes (7)
Toxicity As Assessed By the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Number of patients assigned chemotherapy who experienced grade 3 or higher CTC AE toxicity.
Measured: During planned six cycles of chemotherapy
Pathological Features Present At Diagnosis - Posterior Uveal Invasion (PVI)
Proportion of patients who had posterior uveal invasion at enrollment.
Measured: At enrollment
Pathological Features Present At Diagnosis - Tumor Involving the Optic Nerve Posterior to the Lamina Cribrosa (LC) as an Independent Finding
Proportion of patients with tumor involving the optic nerve posterior to the lamina cribrosa as an independent.
Measured: At enrollment
Pathological Features Present at Diagnosis - Scleral Invasion (SI)
Proportion of patients that had scleral invasion at enrollment.
Measured: At enrollment
Pathological Features Present At Diagnosis - Anterior Chamber Seeding (ACS)
Proportion of patients who had anterior chamber seeding at enrollment.
Measured: At enrollment
Pathological Features Present At Diagnosis - Iris Infiltration (II)
Proportion of patients who had iris infiltration at enrollment.
Measured: At enrollment
Pathological Features Present At Diagnosis - Ciliary Body Infiltration (CBI)
Proportion of patients who had ciliary body infiltration at enrollment.
Measured: At Enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2006 (estimated)
- Study startDec 2005
- Primary completionSep 2011
- Study completion30 Sep 2020
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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 331 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Murali Chintagumpala, MD, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00335738
- Sponsor's protocol ID
- ARET0332
- Other IDs
- NCI-2009-00423, CDR0000483043, U10CA098543, COG-ARET0332
- Status last verified
- Mar 2018
- First submitted
- 8 Jun 2006
- Last updated
- 18 Feb 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 18 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of Unilateral Retinoblastoma With and Without Histopathologic High-Risk Features and the Role of Adjuvant Chemotherapy
- ClinicalTrials.gov ID
- NCT00335738
- Acronym / sponsor ID
- ARET0332
- Conditions
- Intraocular Retinoblastoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 331 participants (actual)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Dec 2005
- Primary completion
- Sep 2011 (actual)
- Study completion
- 30 Sep 2020 (actual)
- First posted
- 12 Jun 2006 (estimated)
- Results
- Posted 17 Apr 2018
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 vincristine, carboplatin, and etoposide to see how well they work compared to observation only in treating patients who have undergone surgery for newly diagnosed retinoblastoma. Drugs used in chemotherapy, such as vincristine, carboplatin, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) after surgery may kill any tumor cells that remain after surgery. Sometimes, after surgery, no additional treatment is needed for the tumor until it progresses. In this case, observation may be sufficient.
Detailed description
OBJECTIVES:
- Prospectively determine the prevalence of high-risk histopathologic features, such as choroidal involvement, optic nerve invasion, and scleral and anterior segment involvement, in patients with newly diagnosed unilateral retinoblastoma who have undergone enucleation.
II. Demonstrate that patients without certain high-risk features can be successfully treated with enucleation alone by estimating the event-free survival (EFS) (where an event is defined as the occurrence of extraocular or metastatic disease) and overall survival (OS).
III. Estimate the EFS and OS of patients with specific high-risk features who are uniformly treated with adjuvant chemotherapy comprising vincristine, carboplatin, and etoposide.
IV. Estimate the incidence of toxicities associated with the proposed adjuvant chemotherapy regimen.
OUTLINE: This is a prospective, nonrandomized, multicenter study. Patients are assigned to 1 of 2 groups according to presence of high-risk histopathologic features.
GROUP 1 (high-risk features): Patients receive vincristine IV and carboplatin IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
GROUP 2 (no high-risk features): Patients undergo observation periodically for at least 5 years.
GROUP 3 (no consensus regarding high risk features can be reached): Patients undergo Group 1 chemotherapy or observation according to institutional high-risk feature assessment.
After completion of study treatment, patients in group 1 are followed periodically for at least 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 (identified by central review as high risk) | Experimental | Drug: liposomal vincristine sulfate, Drug: carboplatin, Drug: etoposideIncludes patients who may or may not require chemotherapy. Patients who require chemotherapy receive vincristine IV and carboplatin IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity and patients who complete chemotherapy are followed after completion of therapy periodically for at least 5 years. Patients who do not require chemotherapy undergo observation periodically for at least 5 years. |
| Group 2 (identified by central review as not high risk) | No intervention | –Patients undergo observation periodically for at least 5 years. |
Who may qualify
- Ages
- Up to 6 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (35 listed)
- Newly diagnosed unilateral retinoblastoma
- Underwent enucleation as primary therapy within the past 5 weeks
- Disease with or without high-risk histopathologic features
- No evidence of extraocular retinoblastoma clinically, by CT scan, or by MRI of the brain and orbits with and without gadolinium
- No tumor at the cut end of the optic nerve on any eye enucleated as evidenced by histologic examination prior to study entry
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 | Group 1 (identified by central review as high risk) |
| carboplatinAlso: Carboplat, CBDCA, JM-8, ParaplatGiven IV | Drug | Group 1 (identified by central review as high risk) |
| etoposideAlso: EPEG, VP-16, VP-16-213Given IV | Drug | Group 1 (identified by central review as high risk) |
Primary outcome
Event-free Survival (EFS)
Time frame: At 2 years
EFS distributions will be estimated by the Kaplan-Meier method for patients with high risk features according to central review and treated with adjuvant chemotherapy and separately for subjects with central review recommendation of enucleation alone.
Overall Survival (OS)
Time frame: At 2 Years
OS distributions will be estimated by the Kaplan-Meier method for patients with high risk features according to central review and treated with adjuvant chemotherapy and separately for subjects with central review recommendation of enucleation alone.
7 secondary outcomes
Toxicity As Assessed By the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Time frame: During planned six cycles of chemotherapy
Pathological Features Present At Diagnosis - Posterior Uveal Invasion (PVI)
Time frame: At enrollment
Pathological Features Present At Diagnosis - Tumor Involving the Optic Nerve Posterior to the Lamina Cribrosa (LC) as an Independent Finding
Time frame: At enrollment
Pathological Features Present at Diagnosis - Scleral Invasion (SI)
Time frame: At enrollment
Pathological Features Present At Diagnosis - Anterior Chamber Seeding (ACS)
Time frame: At enrollment
Pathological Features Present At Diagnosis - Iris Infiltration (II)
Time frame: At enrollment
Pathological Features Present At Diagnosis - Ciliary Body Infiltration (CBI)
Time frame: At Enrollment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data ArchiveLink 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.
Murali Chintagumpala, MD principal investigator
Children's Oncology Group
56 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing liposomal vincristine sulfate, carboplatin and etoposide in people with Intraocular Retinoblastoma, run by Children's Oncology Group at 56 sites in 5 countries.
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 35 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 18 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 56 sites in United States, Australia, Canada, New Zealand, India. 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 17 Apr 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?
Event-free Survival (EFS) (time frame: At 2 years). 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 18 Feb 2021.