Intravitreal Carboplatin for the Treatment of Participants With Recurrent or Refractory Intraocular Retinoblastoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Number of participants who develop dose-limiting toxicity (DLT)
研究概览
简要总结
Retinoblastoma (RB) is the most common intraocular tumor of childhood. Recurrent or refractory disease following therapy most often occurs due to persistence of vitreous disease and/or retinal reactivation of the main tumor mass. With this treatment protocol, investigators seek to identify a less invasive method of local drug delivery that does not disrupt the eye's integrity.
PRIMARY OBJECTIVE:
- To determine the safety and toxicity profile associated with intravitreal carboplatin for the treatment of recurrent or progressive intraocular retinoblastoma with vitreous seeding.
SECONDARY OBJECTIVES:
- To estimate the ocular salvage rate after treatment with intravitreal carboplatin in patients with recurrent or progressive intraocular retinoblastoma with vitreous seeding.
- To evaluate the effects of intravitreal carboplatin therapy on the histopathology of eyes enucleated for progressive or recalcitrant disease while on therapy.
详细描述
The eye(s) will be sterilized prior to injection. Aqueous fluid (0.1-0.15ml) will be withdrawn and sent for pathology review. Carboplatin diluted in normal saline will be administered via intravitreal injection under anesthesia once to each eligible eye approximately every 14 days. Following the injection, triple freeze/thaw cryotherapy is applied to the injection site and the eye is washed with water. The eye is gently "shaken" in all directions to evenly distribute the drug.
This trial will use a traditional phase I design for dose de-escalation with two dose levels. The first 6 patients will be enrolled at dose level 1 and will be observed for dose-limiting toxicity (DLT) throughout the treatment period up to approximately 5 months after start of therapy. If 0-2 (of the first 6) participants experience DLT, a second cohort of 6 patients will be enrolled at the same dose level 1. Study accrual would be completed at 12.
However, if 3 or more of the first 6 patients experience DLT at dose level 1, the dose level would be de-escalated to level -1 and 6 patients enrolled at this level (dose -1). If 0-2 patients experience DLT at dose level -1, a second cohort of 6 patients will be enrolled at dose level -1, and the study accrual would be complete. If 3 or more patients experience DLT at dose level -1, accrual would also be complete.
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
- •Refractory or recurrent retinoblastoma with vitreous seeding meeting eligibility criteria by ultrasonic biomicroscopy performed during examination under anesthesia (EUA) by an ophthalmologist:
- •At least three consecutive clock hours of disease-free, attached peripheral retina through which the intraocular injection may be administered.
- •Absence of invasion in anterior and posterior chamber.
- •Absence of anterior hyaloid detachment.
- •Absence of retinal detachment at the entry site.
- •Absence of tumor at the entry site.
- •ECOG Performance Score must be ≤ 2 within two weeks prior to registration.
- •Participants must have an adequate liver function, as defined by bilirubin ≤3 x upper limit of normal (ULN), and SGOT and SGPT ≤3 x ULN.
- •Participants must have adequate renal function as defined by serum creatinine ≤3 x ULN for age.
- •Legal guardians must sign an informed consent indicating that they are aware of this study, the possible benefits, and toxic side effects. Legal guardians will be given a signed copy of the consent form.
排除标准
- •Presence of metastatic disease or gross orbital involvement.
- •Participants must not have an invasive infection at time of protocol entry.
- •Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.
研究组 & 干预措施
Treatment
Participants with retinoblastoma that is refractory or has relapsed inside the eye.
Interventions: Carboplatin, Maxitrol® , focal therapy, plaque radiotherapy.
干预措施: Carboplatin (Drug)
Treatment
Participants with retinoblastoma that is refractory or has relapsed inside the eye.
Interventions: Carboplatin, Maxitrol® , focal therapy, plaque radiotherapy.
干预措施: Maxitrol® (Drug)
Treatment
Participants with retinoblastoma that is refractory or has relapsed inside the eye.
Interventions: Carboplatin, Maxitrol® , focal therapy, plaque radiotherapy.
干预措施: Focal Therapy (Procedure)
Treatment
Participants with retinoblastoma that is refractory or has relapsed inside the eye.
Interventions: Carboplatin, Maxitrol® , focal therapy, plaque radiotherapy.
干预措施: Plaque Radiotherapy (Procedure)
结局指标
主要结局
Number of participants who develop dose-limiting toxicity (DLT)
时间窗: From baseline through end of therapy (up to 5 months)
DLTs are defined as any of the following: uveitis, sterile or infectious endophthalmitis, retinopathy or rhegmatogenous retinal detachment, massive vitreous hemorrhage that obscures direct visualization of the retina/tumor, and/or cataract that threatens the visual axis or view by treating physician. Grade 3 or 4 allergic reactions should lead to discontinuation of intravitreal carboplatin injections. Patients who have grade 3 or 4 allergic reactions will not be evaluable for this objective and will be replaced.
次要结局
未报告次要终点