Brief Title
Study of Treatment for Patients With Cancer of the Eye -Retinoblastoma
Official Title
Protocol for the Study and Treatment of Patients With Intraocular Retinoblastoma
Brief 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. 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 Phase
Phase 3
Study Type
Interventional
Primary Outcome
Stratum B Response to Window Therapy
Secondary Outcome
Stratum B Response Rate of Early Stage Eyes to Window Therapy
Condition
Retinoblastoma
Intervention
Enucleation
Study Arms / Comparison Groups
Stratum A
Description: 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
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Procedure
Estimated Enrollment
107
Start Date
April 7, 2005
Completion Date
January 2024
Primary Completion Date
November 2013
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- Previously treated patients
- Presence of metastatic disease or orbital involvement
- Patients must not have an invasive infection at time of protocol entry.
Gender
All
Ages
N/A - N/A
Accepts Healthy Volunteers
No
Contacts
Ibrahim Qaddoumi, M.D., ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00186888
Organization ID
RET5
Secondary IDs
P01CA023099
Responsible Party
Sponsor
Study Sponsor
St. Jude Children's Research Hospital
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Ibrahim Qaddoumi, M.D., Principal Investigator, St. Jude Children's Research Hospital
Verification Date
January 2023