A Study of Unilateral Retinoblastoma With and Without Histopathologic High-Risk Features and the Role of Adjuvant Chemotherapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 331
- 试验地点
- 56
- 主要终点
- Event-free Survival (EFS)
研究概览
简要总结
This phase III trial is studying vincristine, carboplatin, and etoposide to see how well they work compared to observation only in treating patients who have undergone surgery for newly diagnosed retinoblastoma. Drugs used in chemotherapy, such as vincristine, carboplatin, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) after surgery may kill any tumor cells that remain after surgery. Sometimes, after surgery, no additional treatment is needed for the tumor until it progresses. In this case, observation may be sufficient.
详细描述
OBJECTIVES:
I. Prospectively determine the prevalence of high-risk histopathologic features, such as choroidal involvement, optic nerve invasion, and scleral and anterior segment involvement, in patients with newly diagnosed unilateral retinoblastoma who have undergone enucleation.
II. Demonstrate that patients without certain high-risk features can be successfully treated with enucleation alone by estimating the event-free survival (EFS) (where an event is defined as the occurrence of extraocular or metastatic disease) and overall survival (OS).
III. Estimate the EFS and OS of patients with specific high-risk features who are uniformly treated with adjuvant chemotherapy comprising vincristine, carboplatin, and etoposide.
IV. Estimate the incidence of toxicities associated with the proposed adjuvant chemotherapy regimen.
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
- 年龄范围
- — 至 6 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly diagnosed unilateral retinoblastoma
- •Underwent enucleation as primary therapy within the past 5 weeks
- •Must enroll and submit pathology slides within 21 days of enucleation
- •Adjuvant chemotherapy must begin within 35 days after enucleation
- •Disease with or without high-risk histopathologic features
- •High-risk features are defined as any of the following:
- •Posterior uveal invasion (includes choroidal invasion)
- •Any degree of concomitant choroid and/or optic nerve involvement
- •Tumor involving the optic nerve posterior to the lamina cribrosa as an independent finding
- •Scleral invasion
- •Anterior chamber seeding
- •Ciliary body infiltration
- •Iris infiltration
- •No evidence of extraocular retinoblastoma clinically, by CT scan, or by MRI of the brain and orbits with and without gadolinium
- •No tumor at the cut end of the optic nerve on any eye enucleated as evidenced by histologic examination prior to study entry
- •No systemic metastases as evidenced by bone marrow scan, bone scan, or any other additional test at study entry
- •Lansky performance status 50-100%
- •Hemoglobin > 8 g/dL
- •Absolute neutrophil count ≥ 1,000/mm³
- •Platelet count ≥ 100,000/mm³
- •Creatinine adjusted according to age as follows:
- •No greater than 0.4 mg/dL (≤ 5 months)
- •No greater than 0.5 mg/dL (6 months -11 months)
- •No greater than 0.6 mg/dL (1 year-23 months)
- •No greater than 0.8 mg/dL (2 years-5 years)
- •No greater than 1.0 mg/dL (6 years-9 years)
- •No greater than 1.2 mg/dL (10 years-12 years)
- •No greater than 1.4 mg/dL (13 years and over [female])
- •No greater than 1.5 mg/dL (13 years to 15 years [male])
- •No greater than 1.7 mg/dL (16 years and over [male])
- •Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
- •AST or ALT < 2.5 times ULN for age
- •No prior therapy other than enucleation
- •No prior chemotherapy
排除标准
- 未提供
研究组 & 干预措施
Group 1 (identified by central review as high risk)
Includes patients who may or may not require chemotherapy. Patients who require chemotherapy receive vincristine IV and carboplatin IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity and patients who complete chemotherapy are followed after completion of therapy periodically for at least 5 years. Patients who do not require chemotherapy undergo observation periodically for at least 5 years.
干预措施: liposomal vincristine sulfate (Drug)
Group 1 (identified by central review as high risk)
Includes patients who may or may not require chemotherapy. Patients who require chemotherapy receive vincristine IV and carboplatin IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity and patients who complete chemotherapy are followed after completion of therapy periodically for at least 5 years. Patients who do not require chemotherapy undergo observation periodically for at least 5 years.
干预措施: carboplatin (Drug)
Group 1 (identified by central review as high risk)
Includes patients who may or may not require chemotherapy. Patients who require chemotherapy receive vincristine IV and carboplatin IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity and patients who complete chemotherapy are followed after completion of therapy periodically for at least 5 years. Patients who do not require chemotherapy undergo observation periodically for at least 5 years.
干预措施: etoposide (Drug)
结局指标
主要结局
Event-free Survival (EFS)
时间窗: At 2 years
EFS distributions will be estimated by the Kaplan-Meier method for patients with high risk features according to central review and treated with adjuvant chemotherapy and separately for subjects with central review recommendation of enucleation alone.
Overall Survival (OS)
时间窗: At 2 Years
OS distributions will be estimated by the Kaplan-Meier method for patients with high risk features according to central review and treated with adjuvant chemotherapy and separately for subjects with central review recommendation of enucleation alone.
次要结局
- Toxicity As Assessed By the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0(During planned six cycles of chemotherapy)
- Pathological Features Present At Diagnosis - Posterior Uveal Invasion (PVI)(At enrollment)
- Pathological Features Present At Diagnosis - Tumor Involving the Optic Nerve Posterior to the Lamina Cribrosa (LC) as an Independent Finding(At enrollment)
- Pathological Features Present at Diagnosis - Scleral Invasion (SI)(At enrollment)
- Pathological Features Present At Diagnosis - Anterior Chamber Seeding (ACS)(At enrollment)
- Pathological Features Present At Diagnosis - Iris Infiltration (II)(At enrollment)
- Pathological Features Present At Diagnosis - Ciliary Body Infiltration (CBI)(At Enrollment)