RetinoblastomaPhase 3NCT00186888
Study of Treatment for Patients With Cancer of the Eye -Retinoblastoma
A Phase 3 study testing Enucleation, Vincristine, Carboplatin and Focal Therapies in people with Retinoblastoma and Retinal Neoplasm, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial summary
Retinoblastoma is a childhood cancer which affects the retina of the eye. The retina is the light sensitive layer of tissue that lines the back of the eyeball; sends visual messages through the optic nerve to the brain. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Retinoblastoma, Retinal Neoplasm
- What is being tested?
- Enucleation, Vincristine, Carboplatin and Focal Therapies
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 107 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Apr 2005to 12 Nov 2024
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Must have newly diagnosed intraocular retinoblastoma, previously untreated. Patients previously diagnosed with unilateral retinoblastoma treated surgically (or with focal therapies), who develop asynchronous involvement of the contralateral eye, will be eligible for study.
- Must have a life expectancy of at least 8 weeks.
- Must have Performance Status (ECOG) of 0-2.
- Patients must have an adequate liver function, as defined by bilirubin less than or equal to 3 x normal, and SGOT and SGPT less than or equal to 3x normal.
- Patients must have adequate renal function as defined by serum creatinine less than or equal to 3x normal for age.
- Legal guardians must sign an informed consent indicating that they are aware of this study, its possible benefits, and toxic side effects. Legal guardians will be given a copy of the consent form.
Who cannot join
- Previously treated patients
- Presence of metastatic disease or orbital involvement
- Patients must not have an invasive infection at time of protocol entry.
Trial locations and contacts
1 site in 1 country.
United States1 site
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
About this study
Official title: Protocol for the Study and Treatment of Patients With Intraocular Retinoblastoma
Retinoblastoma is a childhood cancer which affects the retina of the eye. The retina is the light sensitive layer of tissue that lines the back of the eyeball; sends visual messages through the optic nerve to the brain. When only one eye is affected, this is known as unilateral retinoblastoma and when both eyes are affected, it is called bilateral retinoblastoma. Treatment for retinoblastoma is individualized for each patient and is based on the form and the stage of the disease (inside the eye or has moved outside). The main goal is always to cure the cancer, and save the life of the child. Treatments are also designed with the hope of saving the vision, while completely destroying the tumor. Therapies may involve surgery, chemotherapy, radiation, and other treatments called focal treatments. Focal treatments may be laser therapy, freezing, or heat treatments meant to shrink and kill the tumor.
In this study, researchers want to investigate how different participants respond to different therapies that are individualized specifically for them. Participants will be divided into three main groups, depending on whether the disease is unilateral or bilateral, and the stage of the disease. One of the main objectives of the study is to investigate how advanced tumors in children with bilateral disease respond to a new combination of chemotherapy with topotecan and vincristine, with G-CSF support. In order to improve results, some children with very advanced disease may receive carboplatin chemotherapy given around the eye at the same time that they receive topotecan by vein. Also, because children with retinoblastoma are diagnosed so early in life and the vision may be significantly impaired, this study will investigate how children develop and how the brain adjusts and compensates for the visual deficits. Finally, this study also investigates the biology of retinoblastoma, in order to understand better how this cancer develops.
Read the detailed description
This study will determine the following:
PRIMARY OBJECTIVE:
- To estimate the ocular survival and event-free survival of bilateral disease patients with advanced intraocular retinoblastoma in either eye (R-E IV-V) responding to the vincristine/topotecan window, with alternating cycles of vincristine and carboplatin with vincristine, topotecan, and periocular carboplatin, with intensive focal treatments.
SECONDARY OBJECTIVES:
- To estimate the ocular survival of eye and event-free survival of eye of bilateral disease patients with advanced intraocular retinoblastoma in either eye (R-E IV-V) responding to the vincristine/topotecan window, with alternating cycles of vincristine and carboplatin with vincristine, topotecan, and periocular carboplatin, with intensive focal treatments.
- To estimate the ocular survival and event free survival of patients with advanced intraocular retinoblastoma (R-E IV-V) not responding to the vincristine/topotecan window, with a combination of vincristine, carboplatin, etoposide, and periocular carboplatin, with intensive focal treatments.
- To estimate the ocular survival and event free survival of eye of patients with advanced intraocular retinoblastoma (R-E IV-V) not responding to the vincristine/topotecan window, with a combination of vincristine, carboplatin, etoposide, and periocular carboplatin, with intensive focal treatments.
- To estimate the ocular survival and event-free survival of patients with early stage intraocular retinoblastoma (R-E I-III) with vincristine and carboplatin with intensive focal treatments.
- To estimate the ocular survival of eye and event-free survival of eye of patients with early stage intraocular retinoblastoma (R-E I-III) with vincristine and carboplatin with intensive focal treatments.
- To estimate the response rate of early stage eyes (R-E I-III) in patients with contralateral advanced disease treated with vincristine and topotecan.
- To estimate the ocular survival and event-free survival of early stage eyes (R-E I-III) of patients with contralateral advanced disease treated with vincristine and topotecan.
- To describe the outcome of intraocular retinoblastoma with respect to the new International Classification for Intraocular Retinoblastoma and the AJCC.
- To describe primary visual cortex function in patients with unilateral and bilateral retinoblastoma.
- To describe the cognitive, adaptive, and social/emotional development of children with retinoblastoma.
- To describe changes in the pineal gland during treatment in patients with bilateral retinoblastoma.
- To assess the relation between CYP3A4/5 genotype and the pharmacokinetics and pharmacodynamics of topotecan.
- To assess the relation between ABCG2 genotype and the pharmacokinetics and pharmacodynamics of topotecan.
- To determine if carboplatin can produce changes in cochlear function that are detectable with measurement of otoacoustic emissions.
- To evaluate the need for and feasibility of starting early intervention support during the first year after the diagnosis of retinoblastoma.
EXPLORATORY OBJECTIVES:
- To provide insight into molecular pathogenesis of retinoblastoma.
- To describe the incidence and type of germline mutations of the RB gene in patients with retinoblastoma.
- Conditions
- Retinoblastoma, Retinal Neoplasm
- Being tested
- Enucleation, Vincristine, Carboplatin, Focal Therapies, External Beam Radiation, Vincristine and Topotecan
- Keywords
- Cancer of the Eye, Eye Enucleation
- Medical subject headings
- Retinoblastoma, Retinal Neoplasms, Eye Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnucleationProcedure or surgery
Enucleation (possibly associated with all treatment strata/arms. For Stratum A, patients with bilateral disease will have surgery to remove the advanced eye before chemotherapy, or patients that have disease progression after chemotherapy may have surgery to remove the affected eye.
For Stratum B, Surgical removal of the affected eye may be required in cases of disease progression For Stratum C, first intervention is removal of the affected eye.
Vincristine, CarboplatinDrug
Also called Oncovin + Paraplatin
(Stratum A subjects receive 8 courses every 3-4 weeks, Stratum B subjects receive this combination for Courses 3, 4, 6, 7, 9, and 10 after the window, if they respond to window therapy) Vincristine dosage< 12 months of age: 0.05 mg/kg i.v. day 1, ≥ 12 months of age: 1.5 mg/m2 i.v. day 1 (max. dose 2 mg) Carboplatin will be administered i.v. to achieve an AUC of 6.5 mg/ml/min, day 1.
Focal TherapiesProcedure or surgery
Method will be at the discretion of the treating team, used after second course of chemotherapy. Cryotherapy- freezing of affected tissue, Laser photocoagulation- using lasers to destroy affected tissue, Thermotherapy and thermochemotherapy- using heat or heat/chemotherapy combination to destroy diseased tissue, and Episcleral plaque brachytherapy- radiation insertions in the diseased area to destroy affected tissue.
External Beam RadiationRadiation
44-46 Gy administered using standard practices , limiting dose to normal tissues to subjects with recurrent or progressive disease not considered controllable with focal treatments, Stratum B subjects with suspected active disease after completing therapy, or patients considered to have high-risk disease.
Vincristine and TopotecanDrug
Also called Oncovin + Hycamtin
(Stratum B subjects receive two up-front courses of vincristine and topotecan, given in 21-day intervals, then those who respond receive 3 additional courses (courses 5, 8, and 11) after the window. Dosages are the same for both window and subsequent courses: Vincristine: < 12 months of age: 0.05 mg/kg i.v. day 1, ≥ 12 months of age: 1.5 mg/m2 i.v. day 1 (max. dose 2 mg) Topotecan: TSE of 140 ± 20 ng/ml*hr, daily for 5 consecutive days, infused over 30 minutes.
Vincristine + Carboplatin + EtoposideDrug
Also called Oncovin + Paraplatin + VP-16
Stratum B patients that do not respond to window receive 6 courses of this combination.
Vincristine: < 12 months of age: 0.05 mg/kg i.v. day 1, ≥ 12 months of age: 1.5 mg/m2 i.v. day 1 (max. dose 2 mg) Carboplatin will be administered i.v. to achieve an AUC of 6.5 mg/ml/min, day 1 Etoposide, < 12 months of age: 3.3 mg/kg/d i.v. days 1 - 3, ≥ 12 months of age: 100 mg/m2/d i.v. days 1 - 3
vincristine, cyclophosphamide, and doxorubicinDrug
Also called Onconvin and Cytoxan and Adriamycin
(High risk Stratum C patients in courses 2, 4, and 6 after enucleation, intermediate risk stratum C patients for four consecutive courses after enucleation) Vincristine: < 12 months of age: 0.05 mg/kg i.v. day 1, ≥ 12 months of age: 1.5 mg/m2 i.v. day 1 (max. dose 2 mg) Cyclophosphamide: < 12 months of age: 40 mg/kg i.v. day 1, ≥ 12 months of age: 1,200 mg/m2 i.v. day 1, MESNA 200 mg/m2 at 0, 3, 6, and 9 hours Doxorubicin < 12 months of age: 1.5 mg/kg i.v. day 1, ≥ 12 months of age: 45 mg/m2 i.v. day 1
Vincristine, Carboplatin and EtoposideDrug
Also called Onconvin and Paraplatin and Vepesid
High risk Stratum C patients in courses 1, 3, and 5 after enucleation: Vincristine: < 12 months of age: 0.05 mg/kg i.v. day 1, ≥ 12 months of age: 1.5 mg/m2 i.v. day 1 (max. dose 2 mg) Carboplatin will be administered i.v. to achieve an AUC of 6.5 mg/ml/min, day 1 Etoposide, < 12 months of age: 3.3 mg/kg/d i.v. days 1 - 3, ≥ 12 months of age: 100 mg/m2/d i.v. days 1 - 3
Periocular carboplatinProcedure or surgery
Also called Paraplatin
Periocular (subtenon) carboplatin 20 mg, one injection, in courses 5, 8, and 11 in patients responding to the VT window, and in courses 1, 3, and 6 of VCE in patients not responding to the VT window, when active vitreous disease is present. Carboplatin 20 mg will be diluted in 2 mL of NS or D5W and given by subtenon administration while the patient is under general anesthesia.
G-CSFOther
Also called Filgrastim, Neupogen
G-CSF (5 mcg/kg/day), will be administered starting 24-36 hours after the completion of each course of chemotherapy, for 7 to 10 days, until ANC is > 2,000/mL in one occasion after the expected nadir.
| Study group | Role | What they receive |
|---|---|---|
| Stratum A | Other | Patients with early bilateral or unilateral, or patients with bilateral that have already had the advanced eye enucleated. Treatment included vincristine and carboplatin for 8 courses, given at 3-4 week intervals. Focal therapies any time after second course can include cryotherapy, laser photocoagulation, thermotherapy, and plaque radiotherapy Receives: Procedure: Enucleation; Drug: Vincristine, Carboplatin; Procedure: Focal Therapies; Radiation: External Beam Radiation; Other: G-CSF |
| Stratum B | Other | Patients with bilateral disease (at least one advanced stage eye), candidate for conservative management.
Treatment included window treatment with vincristine and topotecan, Followed by 3 more courses of vincristine-topotecan if they had a response to the window+ 6 courses of vincristine and carboplatin. If they do not respond to the window, they receive 6 courses of vincristine, carboplatin, and etoposide. Periocular carboplatin is also given three times, depending on whether they respond to window. External Beam Radiation 44-46 Gy administered using standard practices. Receives: Procedure: Enucleation; Drug: Vincristine, Carboplatin; Procedure: Focal Therapies; Radiation: External Beam Radiation; Drug: Vincristine and Topotecan; Drug: Vincristine + Carboplatin + Etoposide; Procedure: Periocular carboplatin; Other: G-CSF |
| Stratum C | Other | Patients with advanced unilateral advanced intraocular disease. First intervention is enucleation.
If enucleated eye does not have disease outside the retina (low risk), no additional treatment is given.
For patients whose enucleated eye shows tumor outside the retina (intermediate risk), they will receive 4 courses of vincristine, cyclophosphamide, and doxorubicin followed by G-CSF.
For patients with high risk disease (involvement of the sclera, optic nerve at the level of the cut-end), treatment after enucleation is 6 courses of alternating chemotherapy with vincristine, carboplatin, etoposide (VCE) to alternate with vincristine, cyclophosphamide, and doxorubicin (VCD). High risk patients also receive external-beam radiation therapy. Receives: Procedure: Enucleation; Radiation: External Beam Radiation; Drug: vincristine, cyclophosphamide, and doxorubicin; Drug: Vincristine, Carboplatin and Etoposide; Other: G-CSF |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stratum B Response to Window Therapy
The primary outcome is to estimate the proportion of stratum B patients responding to 2 courses of window therapy consisting of vincristine and topotecan. Complete Response is the complete regression of all apparent tumor masses in the funduscopic examination and by MRI and ultrasound (US). Partial Response is defined as greater than 50% (but less than 100%) reduction of the tumor masses in the funduscopic examination and by US and MRI, without the appearance of any new lesions. The response must persist for at least 4 weeks. Stratum A and C did not receive window therapy.
Measured: Six weeks post window therapy
Secondary outcomes (29)
Stratum B Response Rate of Early Stage Eyes to Window Therapy
To estimate the proportion of early stage eyes defined as Reese-Ellsworth Group I, II, or III eyes, that responded to 2 courses of window therapy which consisted of vincristine and topotecan
Measured: Six weeks post window therapy.
Relationship Between Topotecan Clearance (CL) and CYP3A4/5 Genotype in Stratum B Participants.
Blood samples for pharmacokinetic studies were collected at 0 hour (pre-dose), 5 minutes, 1.5 and 2.5 hours after the end of topotecan dose on Course 1 Day 1, Course 2 Day 1, and if further studies were needed, Course 5 Day 1 and Course 8 Day 1. A blood sample for pharmacogenetic studies was collected during the course of therapy on protocol.
Measured: Courses 1, 2, 5, and 8
Relationship Between Topotecan Clearance (CL) and ABCG2/B1 Genotype in Stratum B Participants.
Blood samples for pharmacokinetic studies were collected at 0 hour (pre-dose), 5 minutes, 1.5 and 2.5 hours after the end of topotecan dose on Course 1 Day 1, Course 2 Day 1, and if further studies were needed, Course 5 Day 1 and Course 8 Day 1. A blood sample for pharmacogenetic studies was collected during the course of therapy on protocol.
Measured: Courses 1, 2, 5, and 8
Event-free Survival of Stratum B Patients Responding to Window Treatment
To estimate the 5-year event-free (EFS) survival of bilateral disease patients with advanced intraocular retinoblastoma in either eye (R-E IV-V) responding to the vincristine/topotecan window, with alternating cycles of vincristine and carboplatin with vincristine, topotecan, and periocular carboplatin, with intensive focal treatments.
Event-free survival will be defined per patient as follows: for patients with one advanced stage eye, the time interval from date on study to date of first event (an event includes external beam radiation or enucleation) of advanced stage eyes, time to first event will be used for the analysis. Event-free survival will be estimated using the method of Kaplan and Meier.
Measured: From date on-study to an event or last follow-up
Ocular Survival of Stratum B Patients Responding to Window Treatment
To estimate the 5-year ocular survival of bilateral disease patients with advanced intraocular retinoblastoma in either eye (R-E IV-V) responding to the vincristine/topotecan window, with alternating cycles of vincristine and carboplatin with vincristine, topotecan, and periocular carboplatin, with intensive focal treatments.
Ocular survival will be defined per patient as follows: for patients with one advanced stage eye, the time interval from date on study to date of enucleation of advanced stage eye or date of last follow-up, for patients with two advanced stage eyes, the time to the first enucleation will be used for analysis. Ocular survival will be estimated using the method of Kaplan and Meier. Standard error is 5-year ocular survival
Measured: From date on-study to an event or last follow-up
Event-free Survival of Eyes in Stratum B Patients Responding to Window Treatment
To estimate the 5-year event-free survival (EFS) of eyes of bilateral disease patients with advanced intraocular retinoblastoma in either eye (R-E IV-V) responding to the vincristine/topotecan window, with alternating cycles of vincristine and carboplatin with vincristine, topotecan, and periocular carboplatin, with intensive focal treatments.
Event-free survival of eye will be defined per eye as the time interval from date on study to date of first event (an event includes external beam radiation or enucleation) or to last follow-up date for eyes without events. Event-free survival of eye will be estimated using the method of Kaplan and Meier. Standard error is 5-year EFS.
Measured: From date on-study to an event or last follow-up
Ocular Survival of Eyes in Stratum B Patients Responding to Window Treatment
To estimate the 5-year ocular survival of eye of bilateral disease patients with advanced intraocular retinoblastoma in either eye (R-E IV-V) responding to the vincristine/topotecan window, with alternating cycles of vincristine and carboplatin with vincristine, topotecan, and periocular carboplatin, with intensive focal treatments.
Ocular survival of eye will be defined per eye as the time interval from date on study to date of enucleation or date of last follow-up. Ocular survival of eye will be estimated using the method of Kaplan and Meier. Standard error is 5-year ocular survival.
Measured: From date on-study to an event or last follow-up
Event-free Survival of Stratum B Patients Not Responding to Window Treatment
To estimate the 5-year event free survival of patients with advanced intraocular retinoblastoma (R-E IV-V) not responding to the vincristine/topotecan window, with a combination of vincristine, carboplatin, etoposide, and periocular carboplatin, with intensive focal treatments.
Measured: From date on-study to an event or last follow-up
Ocular Survival of Stratum B Patients Not Responding to Window Treatment
To estimate the 5-year ocular survival of patients with advanced intraocular retinoblastoma (R-E IV-V) not responding to the vincristine/topotecan window, with a combination of vincristine, carboplatin, etoposide, and periocular carboplatin, with intensive focal treatments.
Measured: From date on-study to an event or last follow-up
Event-free Survival of Eyes in Stratum B Patients Not Responding to Window Treatment
To estimate the 5-year event free survival of the eye of patients with advanced intraocular retinoblastoma (R-E IV-V) not responding to the vincristine/topotecan window, with a combination of vincristine, carboplatin, etoposide, and periocular carboplatin, with intensive focal treatments
Measured: From date on-study to an event or last follow-up
Ocular Survival of Eyes in Stratum B Patients Not Responding to Window Treatment
To estimate the 5-year ocular survival of the eye of patients with advanced intraocular retinoblastoma (R-E IV-V) not responding to the vincristine/topotecan window, with a combination of vincristine, carboplatin, etoposide, and periocular carboplatin, with intensive focal treatments
Measured: From date on-study to an event or last follow-up
Event-free Survival of Stratum A Patients
To estimate the 5-year event-free survival of patients with early stage intraocular retinoblastoma (R-E I-III) with vincristine and carboplatin with intensive focal treatments.
Event-free survival will be defined per patient as follows: for patients with one advanced stage eye, the time interval from date on study to date of first event (an event includes external beam radiation or enucleation) of advanced stage eyes, time to first event will be used for the analysis. Event-free survival will be estimated using the method of Kaplan and Meier.
Measured: From date on-study to an event or last follow-up
Ocular Survival of Stratum A Patients
To estimate the 5-year ocular survival of patients with early stage intraocular retinoblastoma (R-E I-III) with vincristine and carboplatin with intensive focal treatments.
Ocular survival will be defined per patient as follows: for patients with one advanced stage eye, the time interval from date on study to date of enucleation of advanced stage eye or date of last follow-up, for patients with two advanced stage eyes, the time to the first enucleation will be used for analysis. Ocular survival will be estimated using the method of Kaplan and Meier.
Measured: From date on-study to an event or last follow-up
Event-free Survival of Eyes of Stratum B Patients
To estimate the 5-year event-free survival of early stage eyes (R-E I-III) of patients with contralateral advanced disease treated with vincristine and topotecan.
Event-free survival of eye will be defined per eye as the time interval from date on study to date of first event (an event includes external beam radiation or enucleation) or to last follow-up date for eyes without events. Event-free survival of eye will be estimated using the method of Kaplan and Meier.
Measured: From date on-study to an event or last follow-up
Ocular Survival of Eyes of Stratum B Patients
To estimate the 5-year ocular survival of early stage eyes (R-E I-III) of patients with contralateral advanced disease treated with vincristine and topotecan.
Ocular survival will be defined per patient as follows: for patients with one advanced stage eye, the time interval from date on study to date of enucleation of advanced stage eye or date of last follow-up, for patients with two advanced stage eyes, the time to the first enucleation will be used for analysis. Ocular survival will be estimated using the method of Kaplan and Meier.
Measured: From date on-study to an event or last follow-up
Event-free Survival of Eyes in Stratum A and Stratum B Patients Based on IC Classification
To describe the 5-year event-free survival of the eyes outcome of intraocular retinoblastoma with respect to the new International Classification (IC) for Intraocular Retinoblastoma and the AJCC.
Patients were re-classified into 2 groups of early (IC groups A and B) and advanced (IC groups C, D, and E) retinoblastoma. Analysis was done at eye level since each eye in the same patient could be a different group. Patients from stratum A and B were analyzed separately.
Three eyes (2 patients) in stratum B received external beam radiation therapy (EBRT) and were also coincident with enucleation surgery, so their event status was not changed. Although the 3 eyes had shorter EFS interval because EBRT occurred (less than 2 years) before the surgery, it did not change the 5-year survival probability.
Measured: From date on-study to an event or last follow-up
Ocular Survival of Eyes in Stratum A and Stratum B Patients Based on IC Classification
To describe the 5-year ocular survival of eyes outcome of intraocular retinoblastoma with respect to the new International Classification (IC) for Intraocular Retinoblastoma and the AJCC.
Patients were re-classified into 2 groups of early (IC groups A and B) and advanced (IC groups C, D, and E) retinoblastoma. Analysis was done at eye level since each eye in the same patient could be a different group. Patients from stratum A and B were analyzed separately.
Three eyes (2 patients) in stratum B received external beam radiation therapy (EBRT) and were also coincident with enucleation surgery, so their event status was not changed. Although the 3 eyes had shorter EFS interval because EBRT occurred (less than 2 years) before the surgery, it did not change the 5-year survival probability.
Measured: From date on-study to an event or last follow-up
Event-free Survival Per Eye in Stratum A and Stratum B Patients Based on AJCC Classification
To describe the 5-year event-free survival of eyes outcome of intraocular retinoblastoma with respect to the new classification of the American Joint Committee on Cancer (AJCC).
For AJCC staging, the patients were re-classified into 2 groups of early (AJCC=1, 1a or 1b) and advanced (AJCC=2, 2a, 2b, 3, 3a, 3b) retinoblastoma. The analysis was done at eye level since each eye in the same patient could be a different group. Patients from stratum A and B were analyzed separately
Measured: From date on-study to an event or last follow-up
Ocular Survival Per Eye in Stratum A and Stratum B Patients Based on AJCC Classification
To describe the 5-year ocular survival of eyes outcome of intraocular retinoblastoma with respect to the new classification of the American Joint Committee on Cancer (AJCC).
For AJCC staging, the patients were classified into 2 groups of early (AJCC=1, 1a or 1b) and advanced (AJCC=2, 2a, 2b, 3, 3a, 3b) retinoblastoma . The analysis was done at eye level since each eye in the same patient could be a different group. Patients from stratum A and B were analyzed separately
Measured: From date on-study to an event or last follow-up
Change in Cognitive Functioning
The Early Learning Composite was assessed with Mullen Scales of Early Learning, a measure of developmental functioning appropriate for use with children from birth through age 5. It is an examiner-administered instrument that uses toys, games, pictures, and other objects to elicit information about a child's language, fine and gross motor skills, and overall early learning capabilities. Raw scores are converted to an age-normed standard score (normative mean = 100, SD = 15) for the overall Early Learning Composite. This measure was given at all time points. Higher scores are indicative of better functioning, with scores from 85-115 in the average range.
Measured: Baseline (at study entry) and at ages 6 months, 1 year, 2 years, 3 years and 5 years
Change in Relevant Daily Living Skills
The Adaptive Behavior composite was measured using the Vineland Scales of Adaptive Behavior (VABS) which is an examiner-administered semi-structured interview that assesses adaptive functioning from birth through adulthood. Subscales including motor skills, communication, socialization, and daily living skills combine into an overall adaptive behavior composite which is an age-normed standard score (normative mean = 100, SD = 15). This measure was given at all time points. Higher scores are indicative of better functioning, with scores from 85-115 in the average range.
Measured: Baseline (at study entry), 6 months, 1 year, 2 years, 3 years, and 5 years
Change in Parent Report of Social-Emotional Factors
This outcome was measured using the Ages and Stages Questionnaire which is a parent-completed measure of a child's social-emotional functioning. Raw scores are calculated and compared to cut-off points by age (6 months = 45; 1 year = 48; 2 years = 50; 3 years = 59; 5 years =70). Higher scores are indicative of more problems with scores above the cut-off indicating significant concerns warranting additional follow-up. Possible scores range from 0 to 200+, depending on the number of items administered, which varies by the age of the child (19 to 33 items). However, the primary use of this tool is as a screener. Thus, typically, scores are interpreted as they compare to the identified cut-offs, with children who score above the cut-off referred for further evaluation. This measure was given at all time points.
Measured: Baseline (at study entry), 6 months, 1 year, 2 years, 3 years, and 5 years
Change in Parenting Stress Index (PSI)
The PSI is a commonly used measure of parenting stress. In 101 questions, the PSI delineates between stress as a function of child characteristics (e.g., adaptability, demandingness, mood; Child Domain) and stress as a function of parent characteristics (e.g., depression, sense of competence, social isolation; Parent Domain), as well as an overall stress score (Total Stress). Raw scores are calculated (normative means: Child Doman = 98.4; Parent Domain = 122.7; Total Stress Score = 221.1). This measure was given at all time points. Scores range from 131-320 for Total Stress, 69-188 for Parent Domain, and 50-145 for Child Domain, with higher scores indicative of greater stress (Total: >260; Parent: >153, Child: >122).
Measured: Baseline (at study entry), 6 months, 1 year, 2 years, 3 years, and 5 years
Assessment of School Readiness
The Bracken Basic Concepts Scale was used to assess school readiness. It is an examiner-administered measure that assesses per-academic skills including letter and number recognition, shapes, colors, and understanding of sizes and comparisons. Raw scores are converted into age-normed scaled scores (normative mean = 10, SD = 3) for the School Readiness Composite. Higher scores are indicative of stronger pre-academic skills, with scores from 7 to 13 within the Average range.
Measured: Patients were assessed at 5 years of age
Number of Participants With Development of Pineal Cysts
The MRI reports from bilateral patients were reviewed and data abstracted regarding pineal gland measurement and information about pineal cysts. The number of participants with change in primary visual cortex function from diagnosis through 6 years after last patient enrollment is reported here.
Measured: At diagnosis through 6 years after last patient enrollment
Number of Participants With Change in Size of Pineal Gland
The MRI reports from bilateral patients were reviewed and data abstracted regarding pineal gland measurement and information about pineal cysts. The number of participants with change in pineal gland size is reported here.
Measured: From diagnosis through 6 years after last patient enrollment
Change in Distortion Product Otoacoustic Emissions (DPOAEs)
For DP_amplitude to be considered valid, a baseline DP_SNR (Distortion Product for Signal-to-noise ratio) for each frequency (1000-8000 Hz) and for each ear (left and right) must be = 6 dB. Any ear with invalid amplitude at baseline for each frequency should be excluded. The DPOAEs amplitude levels were averaged across the right and left ears at each frequency in the patients exhibiting valid DPOAE amplitudes in both ears, resulting in mean DPOAE levels. Subsequently, comparisons between baseline and most recent evaluation (collapsed across ears) for each frequency were made to evaluate if a significant decrease in DPOAE amplitude exists between the two time points.
Measured: From Diagnosis through 5 years after completion of therapy
Mean Primary Visual Cortex Function: Cluster Size
Functional magnetic resonance imagining (fMRI) was used to investigate primary visual cortex (V1) response to visual stimulation in 105 children being treated for intraocular retinoblastoma. Primary visual cortex activity was assessed in each subject using blood oxygenation level-dependent (BOLD) signal. The BOLD signal was analyzed via a general linear model using Statistical Parametric Mapping software (SPM, Wellcome Institute of Neuology, London).
Voxel volume/peak BOLD response is a measurement of the volume of activation of the cortex. There is no known association with visual outcome at this time.
Measured: At diagnosis through 6 years after last patient enrollment
Mean Primary Visual Cortex Function: Maximum T-value
Functional magnetic resonance imagining (fMRI) was used to investigate primary visual cortex (V1) response to visual stimulation in 105 children being treated for intraocular retinoblastoma. Primary visual cortex activity was assessed in each subject using blood oxygenation level-dependent (BOLD) signal. The BOLD signal was analyzed via a general linear model using Statistical Parametric Mapping software (SPM, Wellcome Institute of Neurology, London). The maximum t-statistic in activated cluster (negative BOLD) is provided.
Voxel volume/peak BOLD response is a measurement of the volume of activation of the cortex. There is no known association with visual outcome at this time.
Measured: At diagnosis through 6 years after last patient enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2005 (estimated)
- Study start7 Apr 2005
- Primary completionNov 2013
- Study completion12 Nov 2024
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.
- Publications (1)Papers the sponsor has linked to this study.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Ibrahim Qaddoumi, M.D., Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00186888
- Sponsor's protocol ID
- RET5
- Other IDs
- P01CA023099, NCI-2011-01186
- Status last verified
- Sep 2025
- First submitted
- 12 Sep 2005
- Last updated
- 4 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
King BA, Sahr N, Sykes A, Wilson MW, Brennan RC. Chemoreduction with topotecan and vincristine: Quantifying tumor response in bilateral retinoblastoma patients. Pediatr Blood Cancer. 2021 Apr;68(4):e28882. doi: 10.1002/pbc.28882. Epub 2021 Jan 28.
PubMed 33507604
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Protocol for the Study and Treatment of Patients With Intraocular Retinoblastoma
- ClinicalTrials.gov ID
- NCT00186888
- Acronym / sponsor ID
- RET5
- Conditions
- Retinoblastoma, Retinal Neoplasm
- Keywords
- Cancer of the Eye, Eye Enucleation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 107 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 7 Apr 2005 (actual)
- Primary completion
- Nov 2013 (actual)
- Study completion
- 12 Nov 2024 (actual)
- First posted
- 16 Sep 2005 (estimated)
- Results
- Posted 30 Aug 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Retinoblastoma is a childhood cancer which affects the retina of the eye. The retina is the light sensitive layer of tissue that lines the back of the eyeball; sends visual messages through the optic nerve to the brain. When only one eye is affected, this is known as unilateral retinoblastoma and when both eyes are affected, it is called bilateral retinoblastoma. Treatment for retinoblastoma is individualized for each patient and is based on the form and the stage of the disease (inside the eye or has moved outside). The main goal is always to cure the cancer, and save the life of the child. Treatments are also designed with the hope of saving the vision, while completely destroying the tumor. Therapies may involve surgery, chemotherapy, radiation, and other treatments called focal treatments. Focal treatments may be laser therapy, freezing, or heat treatments meant to shrink and kill the tumor.
In this study, researchers want to investigate how different participants respond to different therapies that are individualized specifically for them. Participants will be divided into three main groups, depending on whether the disease is unilateral or bilateral, and the stage of the disease. One of the main objectives of the study is to investigate how advanced tumors in children with bilateral disease respond to a new combination of chemotherapy with topotecan and vincristine, with G-CSF support. In order to improve results, some children with very advanced disease may receive carboplatin chemotherapy given around the eye at the same time that they receive topotecan by vein. Also, because children with retinoblastoma are diagnosed so early in life and the vision may be significantly impaired, this study will investigate how children develop and how the brain adjusts and compensates for the visual deficits. Finally, this study also investigates the biology of retinoblastoma, in order to understand better how this cancer develops.
Detailed description
This study will determine the following:
PRIMARY OBJECTIVE:
- To estimate the ocular survival and event-free survival of bilateral disease patients with advanced intraocular retinoblastoma in either eye (R-E IV-V) responding to the vincristine/topotecan window, with alternating cycles of vincristine and carboplatin with vincristine, topotecan, and periocular carboplatin, with intensive focal treatments.
SECONDARY OBJECTIVES:
- To estimate the ocular survival of eye and event-free survival of eye of bilateral disease patients with advanced intraocular retinoblastoma in either eye (R-E IV-V) responding to the vincristine/topotecan window, with alternating cycles of vincristine and carboplatin with vincristine, topotecan, and periocular carboplatin, with intensive focal treatments.
- To estimate the ocular survival and event free survival of patients with advanced intraocular retinoblastoma (R-E IV-V) not responding to the vincristine/topotecan window, with a combination of vincristine, carboplatin, etoposide, and periocular carboplatin, with intensive focal treatments.
- To estimate the ocular survival and event free survival of eye of patients with advanced intraocular retinoblastoma (R-E IV-V) not responding to the vincristine/topotecan window, with a combination of vincristine, carboplatin, etoposide, and periocular carboplatin, with intensive focal treatments.
- To estimate the ocular survival and event-free survival of patients with early stage intraocular retinoblastoma (R-E I-III) with vincristine and carboplatin with intensive focal treatments.
- To estimate the ocular survival of eye and event-free survival of eye of patients with early stage intraocular retinoblastoma (R-E I-III) with vincristine and carboplatin with intensive focal treatments.
- To estimate the response rate of early stage eyes (R-E I-III) in patients with contralateral advanced disease treated with vincristine and topotecan.
- To estimate the ocular survival and event-free survival of early stage eyes (R-E I-III) of patients with contralateral advanced disease treated with vincristine and topotecan.
- To describe the outcome of intraocular retinoblastoma with respect to the new International Classification for Intraocular Retinoblastoma and the AJCC.
- To describe primary visual cortex function in patients with unilateral and bilateral retinoblastoma.
- To describe the cognitive, adaptive, and social/emotional development of children with retinoblastoma.
- To describe changes in the pineal gland during treatment in patients with bilateral retinoblastoma.
- To assess the relation between CYP3A4/5 genotype and the pharmacokinetics and pharmacodynamics of topotecan.
- To assess the relation between ABCG2 genotype and the pharmacokinetics and pharmacodynamics of topotecan.
- To determine if carboplatin can produce changes in cochlear function that are detectable with measurement of otoacoustic emissions.
- To evaluate the need for and feasibility of starting early intervention support during the first year after the diagnosis of retinoblastoma.
EXPLORATORY OBJECTIVES:
- To provide insight into molecular pathogenesis of retinoblastoma.
- To describe the incidence and type of germline mutations of the RB gene in patients with retinoblastoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Stratum A | Other | Procedure: Enucleation, Drug: Vincristine, Carboplatin, Procedure: Focal Therapies, Radiation: External Beam Radiation, Other: G-CSFPatients with early bilateral or unilateral, or patients with bilateral that have already had the advanced eye enucleated. Treatment included vincristine and carboplatin for 8 courses, given at 3-4 week intervals. Focal therapies any time after second course can include cryotherapy, laser photocoagulation, thermotherapy, and plaque radiotherapy |
| Stratum B | Other | Procedure: Enucleation, Drug: Vincristine, Carboplatin, Procedure: Focal Therapies, Radiation: External Beam Radiation, Drug: Vincristine and Topotecan, Drug: Vincristine + Carboplatin + Etoposide, Procedure: Periocular carboplatin, Other: G-CSFPatients with bilateral disease (at least one advanced stage eye), candidate for conservative management. Treatment included window treatment with vincristine and topotecan, Followed by 3 more courses of vincristine-topotecan if they had a response to the window+ 6 courses of vincristine and carboplatin. If they do not respond to the window, they receive 6 courses of vincristine, carboplatin, and etoposide. Periocular carboplatin is also given three times, depending on whether they respond to window. External Beam Radiation 44-46 Gy administered using standard practices. |
| Stratum C | Other | Procedure: Enucleation, Radiation: External Beam Radiation, Drug: vincristine, cyclophosphamide, and doxorubicin, Drug: Vincristine, Carboplatin and Etoposide, Other: G-CSFPatients with advanced unilateral advanced intraocular disease. First intervention is enucleation. If enucleated eye does not have disease outside the retina (low risk), no additional treatment is given. For patients whose enucleated eye shows tumor outside the retina (intermediate risk), they will receive 4 courses of vincristine, cyclophosphamide, and doxorubicin followed by G-CSF. For patients with high risk disease (involvement of the sclera, optic nerve at the level of the cut-end), treatment after enucleation is 6 courses of alternating chemotherapy with vincristine, carboplatin, etoposide (VCE) to alternate with vincristine, cyclophosphamide, and doxorubicin (VCD). High risk patients also receive external-beam radiation therapy. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Must have newly diagnosed intraocular retinoblastoma, previously untreated. Patients previously diagnosed with unilateral retinoblastoma treated surgically (or with focal therapies), who develop asynchronous involvement of the contralateral eye, will be eligible for study.
- Must have a life expectancy of at least 8 weeks.
- Must have Performance Status (ECOG) of 0-2.
- Patients must have an adequate liver function, as defined by bilirubin less than or equal to 3 x normal, and SGOT and SGPT less than or equal to 3x normal.
- Patients must have adequate renal function as defined by serum creatinine less than or equal to 3x normal for age.
Key exclusion criteria (3 listed)
- Previously treated patients
- Presence of metastatic disease or orbital involvement
- Patients must not have an invasive infection at time of protocol entry.
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 |
|---|---|---|
| EnucleationEnucleation (possibly associated with all treatment strata/arms. For Stratum A, patients with bilateral disease will have surgery to remove the advanced eye before chemotherapy, or patients that have disease progression after chemotherapy may have surgery to remove the affected eye. For Stratum B, Surgical removal of the affected eye may be required in cases of disease progression For Stratum C, first intervention is removal of the affected eye. | Procedure or surgery | Stratum A, Stratum B, Stratum C |
| Vincristine, CarboplatinAlso: Oncovin + Paraplatin(Stratum A subjects receive 8 courses every 3-4 weeks, Stratum B subjects receive this combination for Courses 3, 4, 6, 7, 9, and 10 after the window, if they respond to window therapy) Vincristine dosage< 12 months of age: 0.05 mg/kg i.v. day 1, ≥ 12 months of age: 1.5 mg/m2 i.v. day 1 (max. dose 2 mg) Carboplatin will be administered i.v. to achieve an AUC of 6.5 mg/ml/min, day 1. | Drug | Stratum A, Stratum B |
| Focal TherapiesMethod will be at the discretion of the treating team, used after second course of chemotherapy. Cryotherapy- freezing of affected tissue, Laser photocoagulation- using lasers to destroy affected tissue, Thermotherapy and thermochemotherapy- using heat or heat/chemotherapy combination to destroy diseased tissue, and Episcleral plaque brachytherapy- radiation insertions in the diseased area to destroy affected tissue. | Procedure or surgery | Stratum A, Stratum B |
| External Beam Radiation44-46 Gy administered using standard practices , limiting dose to normal tissues to subjects with recurrent or progressive disease not considered controllable with focal treatments, Stratum B subjects with suspected active disease after completing therapy, or patients considered to have high-risk disease. | Radiation | Stratum A, Stratum B, Stratum C |
| Vincristine and TopotecanAlso: Oncovin + Hycamtin(Stratum B subjects receive two up-front courses of vincristine and topotecan, given in 21-day intervals, then those who respond receive 3 additional courses (courses 5, 8, and 11) after the window. Dosages are the same for both window and subsequent courses: Vincristine: < 12 months of age: 0.05 mg/kg i.v. day 1, ≥ 12 months of age: 1.5 mg/m2 i.v. day 1 (max. dose 2 mg) Topotecan: TSE of 140 ± 20 ng/ml*hr, daily for 5 consecutive days, infused over 30 minutes. | Drug | Stratum B |
| Vincristine + Carboplatin + EtoposideAlso: Oncovin + Paraplatin + VP-16Stratum B patients that do not respond to window receive 6 courses of this combination. Vincristine: < 12 months of age: 0.05 mg/kg i.v. day 1, ≥ 12 months of age: 1.5 mg/m2 i.v. day 1 (max. dose 2 mg) Carboplatin will be administered i.v. to achieve an AUC of 6.5 mg/ml/min, day 1 Etoposide, < 12 months of age: 3.3 mg/kg/d i.v. days 1 - 3, ≥ 12 months of age: 100 mg/m2/d i.v. days 1 - 3 | Drug | Stratum B |
| vincristine, cyclophosphamide, and doxorubicinAlso: Onconvin and Cytoxan and Adriamycin(High risk Stratum C patients in courses 2, 4, and 6 after enucleation, intermediate risk stratum C patients for four consecutive courses after enucleation) Vincristine: < 12 months of age: 0.05 mg/kg i.v. day 1, ≥ 12 months of age: 1.5 mg/m2 i.v. day 1 (max. dose 2 mg) Cyclophosphamide: < 12 months of age: 40 mg/kg i.v. day 1, ≥ 12 months of age: 1,200 mg/m2 i.v. day 1, MESNA 200 mg/m2 at 0, 3, 6, and 9 hours Doxorubicin < 12 months of age: 1.5 mg/kg i.v. day 1, ≥ 12 months of age: 45 mg/m2 i.v. day 1 | Drug | Stratum C |
| Vincristine, Carboplatin and EtoposideAlso: Onconvin and Paraplatin and VepesidHigh risk Stratum C patients in courses 1, 3, and 5 after enucleation: Vincristine: < 12 months of age: 0.05 mg/kg i.v. day 1, ≥ 12 months of age: 1.5 mg/m2 i.v. day 1 (max. dose 2 mg) Carboplatin will be administered i.v. to achieve an AUC of 6.5 mg/ml/min, day 1 Etoposide, < 12 months of age: 3.3 mg/kg/d i.v. days 1 - 3, ≥ 12 months of age: 100 mg/m2/d i.v. days 1 - 3 | Drug | Stratum C |
| Periocular carboplatinAlso: ParaplatinPeriocular (subtenon) carboplatin 20 mg, one injection, in courses 5, 8, and 11 in patients responding to the VT window, and in courses 1, 3, and 6 of VCE in patients not responding to the VT window, when active vitreous disease is present. Carboplatin 20 mg will be diluted in 2 mL of NS or D5W and given by subtenon administration while the patient is under general anesthesia. | Procedure or surgery | Stratum B |
| G-CSFAlso: Filgrastim, NeupogenG-CSF (5 mcg/kg/day), will be administered starting 24-36 hours after the completion of each course of chemotherapy, for 7 to 10 days, until ANC is > 2,000/mL in one occasion after the expected nadir. | Other | Stratum A, Stratum B, Stratum C |
Primary outcome
Stratum B Response to Window Therapy
Time frame: Six weeks post window therapy
The primary outcome is to estimate the proportion of stratum B patients responding to 2 courses of window therapy consisting of vincristine and topotecan. Complete Response is the complete regression of all apparent tumor masses in the funduscopic examination and by MRI and ultrasound (US). Partial Response is defined as greater than 50% (but less than 100%) reduction of the tumor masses in the funduscopic examination and by US and MRI, without the appearance of any new lesions. The response must persist for at least 4 weeks. Stratum A and C did not receive window therapy.
29 secondary outcomes
Stratum B Response Rate of Early Stage Eyes to Window Therapy
Time frame: Six weeks post window therapy.
Relationship Between Topotecan Clearance (CL) and CYP3A4/5 Genotype in Stratum B Participants.
Time frame: Courses 1, 2, 5, and 8
Relationship Between Topotecan Clearance (CL) and ABCG2/B1 Genotype in Stratum B Participants.
Time frame: Courses 1, 2, 5, and 8
Event-free Survival of Stratum B Patients Responding to Window Treatment
Time frame: From date on-study to an event or last follow-up
Ocular Survival of Stratum B Patients Responding to Window Treatment
Time frame: From date on-study to an event or last follow-up
Event-free Survival of Eyes in Stratum B Patients Responding to Window Treatment
Time frame: From date on-study to an event or last follow-up
Ocular Survival of Eyes in Stratum B Patients Responding to Window Treatment
Time frame: From date on-study to an event or last follow-up
Event-free Survival of Stratum B Patients Not Responding to Window Treatment
Time frame: From date on-study to an event or last follow-up
Ocular Survival of Stratum B Patients Not Responding to Window Treatment
Time frame: From date on-study to an event or last follow-up
Event-free Survival of Eyes in Stratum B Patients Not Responding to Window Treatment
Time frame: From date on-study to an event or last follow-up
Ocular Survival of Eyes in Stratum B Patients Not Responding to Window Treatment
Time frame: From date on-study to an event or last follow-up
Event-free Survival of Stratum A Patients
Time frame: From date on-study to an event or last follow-up
Ocular Survival of Stratum A Patients
Time frame: From date on-study to an event or last follow-up
Event-free Survival of Eyes of Stratum B Patients
Time frame: From date on-study to an event or last follow-up
Ocular Survival of Eyes of Stratum B Patients
Time frame: From date on-study to an event or last follow-up
Event-free Survival of Eyes in Stratum A and Stratum B Patients Based on IC Classification
Time frame: From date on-study to an event or last follow-up
Ocular Survival of Eyes in Stratum A and Stratum B Patients Based on IC Classification
Time frame: From date on-study to an event or last follow-up
Event-free Survival Per Eye in Stratum A and Stratum B Patients Based on AJCC Classification
Time frame: From date on-study to an event or last follow-up
Ocular Survival Per Eye in Stratum A and Stratum B Patients Based on AJCC Classification
Time frame: From date on-study to an event or last follow-up
Change in Cognitive Functioning
Time frame: Baseline (at study entry) and at ages 6 months, 1 year, 2 years, 3 years and 5 years
Change in Relevant Daily Living Skills
Time frame: Baseline (at study entry), 6 months, 1 year, 2 years, 3 years, and 5 years
Change in Parent Report of Social-Emotional Factors
Time frame: Baseline (at study entry), 6 months, 1 year, 2 years, 3 years, and 5 years
Change in Parenting Stress Index (PSI)
Time frame: Baseline (at study entry), 6 months, 1 year, 2 years, 3 years, and 5 years
Assessment of School Readiness
Time frame: Patients were assessed at 5 years of age
Number of Participants With Development of Pineal Cysts
Time frame: At diagnosis through 6 years after last patient enrollment
Number of Participants With Change in Size of Pineal Gland
Time frame: From diagnosis through 6 years after last patient enrollment
Change in Distortion Product Otoacoustic Emissions (DPOAEs)
Time frame: From Diagnosis through 5 years after completion of therapy
Mean Primary Visual Cortex Function: Cluster Size
Time frame: At diagnosis through 6 years after last patient enrollment
Mean Primary Visual Cortex Function: Maximum T-value
Time frame: At diagnosis through 6 years after last patient enrollment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33507604King BA, Sahr N, Sykes A, Wilson MW, Brennan RC. Chemoreduction with topotecan and vincristine: Quantifying tumor response in bilateral retinoblastoma patients. Pediatr Blood Cancer. 2021 Apr;68(4):e28882. doi: 10.1002/pbc.28882. Epub 2021 Jan 28.
- 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.
Ibrahim Qaddoumi, M.D. 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 3 study testing Enucleation, Vincristine, Carboplatin and Focal Therapies in people with Retinoblastoma and Retinal Neoplasm, 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 6 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 4 Sep 2025. 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 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 30 Aug 2011). 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?
Stratum B Response to Window Therapy (time frame: Six weeks post window therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00186888, which also lists 1 linked publication.
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 4 Sep 2025.