A Single Arm Trial of Systemic And Subtenon Chemotherapy For Groups C And D Intraocular Retinoblastoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 11
- 主要终点
- Group D Eyes - Treatment Failure Within One Year
研究概览
简要总结
Phase III trial to determine the effectiveness of combining systemic chemotherapy and subtenon carboplatin with ophthalmic therapy in treating children who have intraocular retinoblastoma. Drugs used in chemotherapy, such as vincristine, carboplatin, and etoposide, work in different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether systemic chemotherapy and subtenon (under the conjunctiva of the eye) carboplatin combined with ophthalmic therapy is effective in treating intraocular (within the eyeball) retinoblastoma.
详细描述
PRIMARY OBJECTIVES:
I. Determine the event-free survival at 12 months of pediatric patients' eyes with group D intraocular retinoblastoma treated with systemic chemotherapy comprising vincristine, carboplatin, and etoposide, subtenon carboplatin, and local ophthalmic therapy. (Event defined for each eye individually as needed for nonprotocol therapy including nonprotocol chemotherapy, enucleation or any external-beam radiation)
SECONDARY OBJECTIVES:
I. Determine the event-free survival at 12 months of pediatric patients' eyes with group C retinoblastoma treated with systemic chemotherapy comprising carboplatin, etoposide, vincristine, subtenon carboplatin, and local ophthalmic therapy.
II. Determine the acute and long-term toxic effects of these regimens in these patients, including visual outcome and incidence of secondary malignancies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of bilateral retinoblastoma with at least 1 eye group C or D intraocular retinoblastoma by ophthalmologic examination, defined by the International Classification System for Intraocular Retinoblastoma as the following:
- •Group C: Discrete localized disease with minimal subretinal and/or vitreous seeding
- •Subretinal fluid, without prior or concurrent seeding, involving ≤ one quarter of the retina
- •Local fine vitreous seeding may be present close to discrete tumor
- •Local subretinal seeding < 3 mm from tumor
- •Group D: Diffuse disease with significant vitreous and/or subretinal seeding
- •Tumor(s) may be massive or diffuse
- •Subretinal fluid, without prior or concurrent seeding, involving up to total retinal detachment
- •Diffuse or massive vitreous disease may include "greasy" seeds or avascular tumor masses
- •Diffuse subretinal seeding may include subretinal plaques or tumor nodules
- •Prior enucleation of 1 eye allowed provided the remaining eye is group C or D
- •No tumor present on histologic examination at the cut end of the optic nerve on any eye enucleated prior to study entry
- •Evidence of choroidal and/or optic nerve invasion past the lumina cribrosa is allowed
- •No extraocular retinoblastoma clinically or by MRI of brain and orbits with and without gadolinium or CT scan with and without contrast of brain and orbits
- •No evidence of systemic metastases by bone marrow, lumbar puncture, bone scan, and/or any other additional test
- •Performance status - Karnofsky 50-100% (over 16 years of age)
- •Performance status - Lansky 50-100% (16 and under)
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
- •AST and ALT < 2.5 times ULN for age
- •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/1.73m^2
- •Not pregnant or nursing
- •Fertile patients must use effective contraception
- •Negative pregnancy test in postmenarchal females
- •No prior chemotherapy
- •No other concurrent chemotherapy
- •No prior radiotherapy
- •No other concurrent radiotherapy
排除标准
- 未提供
研究组 & 干预措施
Treatment (chemotherapy, surgery)
Patients receive liposomal vincristine sulfate IV over 1 minute on day 1 and carboplatin IV over 1 hour and etoposide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 3 and continuing until blood counts recover. Patients receive subtenon carboplatin to each group C or D eye on day 0 or 1prior of courses 2-4 only. Treatment repeats every 28 days for 6 courses in the absence of occurrence of extraocular retinoblastoma or a second malignancy. Beginning with course 3 of systemic chemotherapy, patients undergo local ophthalmic therapy comprising local laser surgery and/or cryosurgery on day 1.
干预措施: liposomal vincristine sulfate (Drug)
Treatment (chemotherapy, surgery)
Patients receive liposomal vincristine sulfate IV over 1 minute on day 1 and carboplatin IV over 1 hour and etoposide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 3 and continuing until blood counts recover. Patients receive subtenon carboplatin to each group C or D eye on day 0 or 1prior of courses 2-4 only. Treatment repeats every 28 days for 6 courses in the absence of occurrence of extraocular retinoblastoma or a second malignancy. Beginning with course 3 of systemic chemotherapy, patients undergo local ophthalmic therapy comprising local laser surgery and/or cryosurgery on day 1.
干预措施: cryosurgery (Procedure)
Treatment (chemotherapy, surgery)
Patients receive liposomal vincristine sulfate IV over 1 minute on day 1 and carboplatin IV over 1 hour and etoposide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 3 and continuing until blood counts recover. Patients receive subtenon carboplatin to each group C or D eye on day 0 or 1prior of courses 2-4 only. Treatment repeats every 28 days for 6 courses in the absence of occurrence of extraocular retinoblastoma or a second malignancy. Beginning with course 3 of systemic chemotherapy, patients undergo local ophthalmic therapy comprising local laser surgery and/or cryosurgery on day 1.
干预措施: laser surgery (Procedure)
Treatment (chemotherapy, surgery)
Patients receive liposomal vincristine sulfate IV over 1 minute on day 1 and carboplatin IV over 1 hour and etoposide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 3 and continuing until blood counts recover. Patients receive subtenon carboplatin to each group C or D eye on day 0 or 1prior of courses 2-4 only. Treatment repeats every 28 days for 6 courses in the absence of occurrence of extraocular retinoblastoma or a second malignancy. Beginning with course 3 of systemic chemotherapy, patients undergo local ophthalmic therapy comprising local laser surgery and/or cryosurgery on day 1.
干预措施: carboplatin (Drug)
Treatment (chemotherapy, surgery)
Patients receive liposomal vincristine sulfate IV over 1 minute on day 1 and carboplatin IV over 1 hour and etoposide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 3 and continuing until blood counts recover. Patients receive subtenon carboplatin to each group C or D eye on day 0 or 1prior of courses 2-4 only. Treatment repeats every 28 days for 6 courses in the absence of occurrence of extraocular retinoblastoma or a second malignancy. Beginning with course 3 of systemic chemotherapy, patients undergo local ophthalmic therapy comprising local laser surgery and/or cryosurgery on day 1.
干预措施: etoposide (Drug)
Treatment (chemotherapy, surgery)
Patients receive liposomal vincristine sulfate IV over 1 minute on day 1 and carboplatin IV over 1 hour and etoposide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 3 and continuing until blood counts recover. Patients receive subtenon carboplatin to each group C or D eye on day 0 or 1prior of courses 2-4 only. Treatment repeats every 28 days for 6 courses in the absence of occurrence of extraocular retinoblastoma or a second malignancy. Beginning with course 3 of systemic chemotherapy, patients undergo local ophthalmic therapy comprising local laser surgery and/or cryosurgery on day 1.
干预措施: filgrastim (Biological)
结局指标
主要结局
Group D Eyes - Treatment Failure Within One Year
时间窗: One year
Each Group D eye will be classified as experiencing failure within one year after start of treatment: yes or no. The method of Rosner et al. (Biometrics v. 38, 105-114, 1982) will be used to model possible dependence between eyes from the same patient. The point estimate of the probability of treatment failure is reported as the "Mean" measure type.
Group C Eyes - Treatment Failure Within One Year
时间窗: One year
Each Group C eye will be classified as experiencing failure within one year after start of treatment: yes or no. The method of Rosner et al. (Biometrics v. 38, 105-114, 1982) will be used to model possible dependence between eyes from the same patient. The point estimate of the probability of treatment failure is reported as the "Mean" measure type.
次要结局
- Event-free Survival (EFS)(One year after study enrollment)
- Patterns of Failure for Group C and Group D in Terms of Vitreous vs Patterns of Failure for Group C and Group D in Terms of Vitreous vs Retinal vs Both as Sites of Recurrence(From the date of enrollment assessed up to 36 months)
- Patterns of Treatment Failure vs. no Treatment Failure for Group C Eyes and Group D Eyes According to Initial Sites of Involvement(From the date of enrollment assessed up to 12 months)
- Toxicity Associated With Chemotherapy(From date of enrollment until termination of protocol therapy assessed up to 72 weeks)