Protocol for the Study and Treatment of Patients With Intraocular Retinoblastoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 107
- 试验地点
- 1
- 主要终点
- Stratum B Response to Window Therapy
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-
- •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.
排除标准
- •Previously treated patients
- •Presence of metastatic disease or orbital involvement
- •Patients must not have an invasive infection at time of protocol entry.
研究组 & 干预措施
Stratum A
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
干预措施: Enucleation (Procedure)
Stratum A
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
干预措施: Vincristine, Carboplatin (Drug)
Stratum A
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
干预措施: Focal Therapies (Procedure)
Stratum A
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
干预措施: External Beam Radiation (Radiation)
Stratum A
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
干预措施: G-CSF (Other)
Stratum B
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.
干预措施: Enucleation (Procedure)
Stratum B
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.
干预措施: Vincristine, Carboplatin (Drug)
Stratum B
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.
干预措施: Focal Therapies (Procedure)
Stratum B
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.
干预措施: External Beam Radiation (Radiation)
Stratum B
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.
干预措施: Vincristine and Topotecan (Drug)
Stratum B
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.
干预措施: Vincristine + Carboplatin + Etoposide (Drug)
Stratum B
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.
干预措施: Periocular carboplatin (Procedure)
Stratum B
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.
干预措施: G-CSF (Other)
Stratum C
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.
干预措施: Enucleation (Procedure)
Stratum C
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.
干预措施: External Beam Radiation (Radiation)
Stratum C
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.
干预措施: vincristine, cyclophosphamide, and doxorubicin (Drug)
Stratum C
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.
干预措施: Vincristine, Carboplatin and Etoposide (Drug)
Stratum C
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.
干预措施: G-CSF (Other)
结局指标
主要结局
Stratum B Response to Window Therapy
时间窗: 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.
次要结局
- Stratum B Response Rate of Early Stage Eyes to Window Therapy(Six weeks post window therapy.)
- Relationship Between Topotecan Clearance (CL) and CYP3A4/5 Genotype in Stratum B Participants.(Courses 1, 2, 5, and 8)
- Relationship Between Topotecan Clearance (CL) and ABCG2/B1 Genotype in Stratum B Participants.(Courses 1, 2, 5, and 8)
- Event-free Survival of Stratum B Patients Responding to Window Treatment(From date on-study to an event or last follow-up)
- Ocular Survival of Stratum B Patients Responding to Window Treatment(From date on-study to an event or last follow-up)
- Event-free Survival of Eyes in Stratum B Patients Responding to Window Treatment(From date on-study to an event or last follow-up)
- Ocular Survival of Eyes in Stratum B Patients Responding to Window Treatment(From date on-study to an event or last follow-up)
- Event-free Survival of Stratum B Patients Not Responding to Window Treatment(From date on-study to an event or last follow-up)
- Ocular Survival of Stratum B Patients Not Responding to Window Treatment(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(From date on-study to an event or last follow-up)
- Ocular Survival of Eyes in Stratum B Patients Not Responding to Window Treatment(From date on-study to an event or last follow-up)
- Event-free Survival of Stratum A Patients(From date on-study to an event or last follow-up)
- Ocular Survival of Stratum A Patients(From date on-study to an event or last follow-up)
- Event-free Survival of Eyes of Stratum B Patients(From date on-study to an event or last follow-up)
- Ocular Survival of Eyes of Stratum B Patients(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(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(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(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(From date on-study to an event or last follow-up)
- Change in Cognitive Functioning(Baseline (at study entry) and at ages 6 months, 1 year, 2 years, 3 years and 5 years)
- Change in Relevant Daily Living Skills(Baseline (at study entry), 6 months, 1 year, 2 years, 3 years, and 5 years)
- Change in Parent Report of Social-Emotional Factors(Baseline (at study entry), 6 months, 1 year, 2 years, 3 years, and 5 years)
- Change in Parenting Stress Index (PSI)(Baseline (at study entry), 6 months, 1 year, 2 years, 3 years, and 5 years)
- Assessment of School Readiness(Patients were assessed at 5 years of age)
- Number of Participants With Development of Pineal Cysts(At diagnosis through 6 years after last patient enrollment)
- Number of Participants With Change in Size of Pineal Gland(From diagnosis through 6 years after last patient enrollment)
- Change in Distortion Product Otoacoustic Emissions (DPOAEs)(From Diagnosis through 5 years after completion of therapy)
- Mean Primary Visual Cortex Function: Cluster Size(At diagnosis through 6 years after last patient enrollment)
- Mean Primary Visual Cortex Function: Maximum T-value(At diagnosis through 6 years after last patient enrollment)