A Trial of Intensive Multi-Modality Therapy for Extra-Ocular Retinoblastoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 73
- 主要终点
- Event-free Survival (EFS)
研究概览
简要总结
This phase III trial is studying the side effects and how well giving combination chemotherapy together with autologous stem cell transplant and/or radiation therapy works in treating young patients with extraocular retinoblastoma. Giving chemotherapy before an autologous stem cell transplant stops the growth of tumor cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and/or bone marrow and stored. More chemotherapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Radiation therapy uses high energy x-rays to kill tumor cells. Giving radiation therapy after combination chemotherapy and/or autologous stem cell transplant may kill any remaining tumor cells.
详细描述
OBJECTIVES:
I. To estimate the proportion of 3 groups of patients with extraocular retinoblastoma (stage 2 and 3: regional extra-ocular disease;, stage 4a: disseminated metastatic disease not involving the central nervous system [CNS]; or stage 4b: patients with CNS disease) who achieve long-term event-free survival after treatment with aggressive multimodality therapy compared to historical controls.
II. To estimate the response rate to the induction phase of the regimen. III. To evaluate the toxicities associated with this regimen.
OUTLINE:
INDUCTION CHEMOTHERAPY: Patients receive vincristine intravenously (IV) on days 0, 7, and 14, cisplatin IV over 6 hours on day 0, cyclophosphamide IV over 1 hour and etoposide IV over 1 hour on days 1 and 2, and filgrastim (G-CSF) subcutaneously (SC) beginning on day 3 and continuing until blood counts recover.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 10 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have histologic or cytologic verification of extra-ocular retinoblastoma; extra-ocular disease includes orbital disease, optic nerve involvement at the surgical margin, regional nodal disease, and/or overt distant metastatic disease (at sites such as bone, bone marrow, liver and/or the central nervous system); patients with trilateral retinoblastoma will also be included in this protocol
- •Patients with a CNS lesion consistent with trilateral or stage 4b disease may be enrolled without tissue confirmation if (1) unequivocal leptomeningeal disease is present on brain or spine magnetic resonance imaging (MRI) scan and/or (2) the primary tumor is at least 2 cm in diameter, predominantly solid, and demonstrates enhancement on the post-gadolinium images; however, even in such cases surgery should be given serious consideration
- •Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
- •No prior chemotherapy or radiotherapy for the extra-ocular retinoblastoma may have been administered prior to entering this study; prior treatment (chemotherapy and/or radiation therapy) for intra-ocular retinoblastoma is permissible
- •Peripheral absolute neutrophil count (ANC) >= 750/uL
- •If the ANC and/or platelet count are not adequate, but due to bone marrow metastatic disease, these criteria will be waived
- •Platelet count >= 75,000/uL (transfusion independent)
- •If the ANC and/or platelet count are not adequate, but due to bone marrow metastatic disease, these criteria will be waived
- •Creatinine clearance OR radioisotope glomerular filtration rate >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
- •0.4 mg/dL (1 month to < 6 months of age)
- •0.5 mg/dL (6 months to < 1 year of age)
- •0.6 mg/dL (1 years to < 2 years of age)
- •0.8 mg/dL (2 years to < 6 years of age)
- •1.0 mg/dL (6 years to < 10 years of age)
- •1.2 mg/dL (10 years to < 13 years of age)
- •1.5 mg/dL (male) or 1.4 mg/dL (female) (13 years to < 16 years of age)
- •1.7 mg/dL (male) or 1.4 mg/dL (female) (>= 16 years of age)
- •Total bilirubin =< 1.5 times upper limit of normal (ULN)
- •Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x upper limit of normal (ULN)
- •All patients and/or their parents or legal guardians must sign a written informed consent
- •All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) for human studies must be met
排除标准
- 未提供
研究组 & 干预措施
Treatment (chemotherapy, radiotherapy, autologous SCI)
INDUCTION: Patients receive vincristine IV; cisplatin IV; cyclophosphamide IV; and G-CSF SC beginning on day 3 and continuing until blood counts recover.
CONSOLIDATION (stage 4a or 4b disease only): Patients receive carboplatin IV; thiotepa IV; and etoposide IV.
AUTOLOGOUS STEM CELL INFUSION (stage 4a or 4b disease only): Patients undergo autologous stem cell infusion on day 0 and receive G-CSF SC beginning on day 1 and continuing until blood counts recover.
RADIOTHERAPY: Patients with stage 2 or 3 disease (orbital and/or regional involvement) undergo radiotherapy to sites that were initially involved beginning within 42 days after the start of course 4 of induction chemotherapy. Patients with stage 4a or 4b disease undergo radiotherapy to sites initially involved based on response beginning approximately 42 days after autologous stem cell infusion.
干预措施: Autologous Bone Marrow Transplantation (Procedure)
Treatment (chemotherapy, radiotherapy, autologous SCI)
INDUCTION: Patients receive vincristine IV; cisplatin IV; cyclophosphamide IV; and G-CSF SC beginning on day 3 and continuing until blood counts recover.
CONSOLIDATION (stage 4a or 4b disease only): Patients receive carboplatin IV; thiotepa IV; and etoposide IV.
AUTOLOGOUS STEM CELL INFUSION (stage 4a or 4b disease only): Patients undergo autologous stem cell infusion on day 0 and receive G-CSF SC beginning on day 1 and continuing until blood counts recover.
RADIOTHERAPY: Patients with stage 2 or 3 disease (orbital and/or regional involvement) undergo radiotherapy to sites that were initially involved beginning within 42 days after the start of course 4 of induction chemotherapy. Patients with stage 4a or 4b disease undergo radiotherapy to sites initially involved based on response beginning approximately 42 days after autologous stem cell infusion.
干预措施: Autologous Hematopoietic Stem Cell Transplantation (Procedure)
Treatment (chemotherapy, radiotherapy, autologous SCI)
INDUCTION: Patients receive vincristine IV; cisplatin IV; cyclophosphamide IV; and G-CSF SC beginning on day 3 and continuing until blood counts recover.
CONSOLIDATION (stage 4a or 4b disease only): Patients receive carboplatin IV; thiotepa IV; and etoposide IV.
AUTOLOGOUS STEM CELL INFUSION (stage 4a or 4b disease only): Patients undergo autologous stem cell infusion on day 0 and receive G-CSF SC beginning on day 1 and continuing until blood counts recover.
RADIOTHERAPY: Patients with stage 2 or 3 disease (orbital and/or regional involvement) undergo radiotherapy to sites that were initially involved beginning within 42 days after the start of course 4 of induction chemotherapy. Patients with stage 4a or 4b disease undergo radiotherapy to sites initially involved based on response beginning approximately 42 days after autologous stem cell infusion.
干预措施: Carboplatin (Drug)
Treatment (chemotherapy, radiotherapy, autologous SCI)
INDUCTION: Patients receive vincristine IV; cisplatin IV; cyclophosphamide IV; and G-CSF SC beginning on day 3 and continuing until blood counts recover.
CONSOLIDATION (stage 4a or 4b disease only): Patients receive carboplatin IV; thiotepa IV; and etoposide IV.
AUTOLOGOUS STEM CELL INFUSION (stage 4a or 4b disease only): Patients undergo autologous stem cell infusion on day 0 and receive G-CSF SC beginning on day 1 and continuing until blood counts recover.
RADIOTHERAPY: Patients with stage 2 or 3 disease (orbital and/or regional involvement) undergo radiotherapy to sites that were initially involved beginning within 42 days after the start of course 4 of induction chemotherapy. Patients with stage 4a or 4b disease undergo radiotherapy to sites initially involved based on response beginning approximately 42 days after autologous stem cell infusion.
干预措施: Cisplatin (Drug)
Treatment (chemotherapy, radiotherapy, autologous SCI)
INDUCTION: Patients receive vincristine IV; cisplatin IV; cyclophosphamide IV; and G-CSF SC beginning on day 3 and continuing until blood counts recover.
CONSOLIDATION (stage 4a or 4b disease only): Patients receive carboplatin IV; thiotepa IV; and etoposide IV.
AUTOLOGOUS STEM CELL INFUSION (stage 4a or 4b disease only): Patients undergo autologous stem cell infusion on day 0 and receive G-CSF SC beginning on day 1 and continuing until blood counts recover.
RADIOTHERAPY: Patients with stage 2 or 3 disease (orbital and/or regional involvement) undergo radiotherapy to sites that were initially involved beginning within 42 days after the start of course 4 of induction chemotherapy. Patients with stage 4a or 4b disease undergo radiotherapy to sites initially involved based on response beginning approximately 42 days after autologous stem cell infusion.
干预措施: Cyclophosphamide (Drug)
Treatment (chemotherapy, radiotherapy, autologous SCI)
INDUCTION: Patients receive vincristine IV; cisplatin IV; cyclophosphamide IV; and G-CSF SC beginning on day 3 and continuing until blood counts recover.
CONSOLIDATION (stage 4a or 4b disease only): Patients receive carboplatin IV; thiotepa IV; and etoposide IV.
AUTOLOGOUS STEM CELL INFUSION (stage 4a or 4b disease only): Patients undergo autologous stem cell infusion on day 0 and receive G-CSF SC beginning on day 1 and continuing until blood counts recover.
RADIOTHERAPY: Patients with stage 2 or 3 disease (orbital and/or regional involvement) undergo radiotherapy to sites that were initially involved beginning within 42 days after the start of course 4 of induction chemotherapy. Patients with stage 4a or 4b disease undergo radiotherapy to sites initially involved based on response beginning approximately 42 days after autologous stem cell infusion.
干预措施: Etoposide (Drug)
Treatment (chemotherapy, radiotherapy, autologous SCI)
INDUCTION: Patients receive vincristine IV; cisplatin IV; cyclophosphamide IV; and G-CSF SC beginning on day 3 and continuing until blood counts recover.
CONSOLIDATION (stage 4a or 4b disease only): Patients receive carboplatin IV; thiotepa IV; and etoposide IV.
AUTOLOGOUS STEM CELL INFUSION (stage 4a or 4b disease only): Patients undergo autologous stem cell infusion on day 0 and receive G-CSF SC beginning on day 1 and continuing until blood counts recover.
RADIOTHERAPY: Patients with stage 2 or 3 disease (orbital and/or regional involvement) undergo radiotherapy to sites that were initially involved beginning within 42 days after the start of course 4 of induction chemotherapy. Patients with stage 4a or 4b disease undergo radiotherapy to sites initially involved based on response beginning approximately 42 days after autologous stem cell infusion.
干预措施: Filgrastim (Biological)
Treatment (chemotherapy, radiotherapy, autologous SCI)
INDUCTION: Patients receive vincristine IV; cisplatin IV; cyclophosphamide IV; and G-CSF SC beginning on day 3 and continuing until blood counts recover.
CONSOLIDATION (stage 4a or 4b disease only): Patients receive carboplatin IV; thiotepa IV; and etoposide IV.
AUTOLOGOUS STEM CELL INFUSION (stage 4a or 4b disease only): Patients undergo autologous stem cell infusion on day 0 and receive G-CSF SC beginning on day 1 and continuing until blood counts recover.
RADIOTHERAPY: Patients with stage 2 or 3 disease (orbital and/or regional involvement) undergo radiotherapy to sites that were initially involved beginning within 42 days after the start of course 4 of induction chemotherapy. Patients with stage 4a or 4b disease undergo radiotherapy to sites initially involved based on response beginning approximately 42 days after autologous stem cell infusion.
干预措施: In Vitro-Treated Peripheral Blood Stem Cell Transplantation (Procedure)
Treatment (chemotherapy, radiotherapy, autologous SCI)
INDUCTION: Patients receive vincristine IV; cisplatin IV; cyclophosphamide IV; and G-CSF SC beginning on day 3 and continuing until blood counts recover.
CONSOLIDATION (stage 4a or 4b disease only): Patients receive carboplatin IV; thiotepa IV; and etoposide IV.
AUTOLOGOUS STEM CELL INFUSION (stage 4a or 4b disease only): Patients undergo autologous stem cell infusion on day 0 and receive G-CSF SC beginning on day 1 and continuing until blood counts recover.
RADIOTHERAPY: Patients with stage 2 or 3 disease (orbital and/or regional involvement) undergo radiotherapy to sites that were initially involved beginning within 42 days after the start of course 4 of induction chemotherapy. Patients with stage 4a or 4b disease undergo radiotherapy to sites initially involved based on response beginning approximately 42 days after autologous stem cell infusion.
干预措施: Radiation Therapy (Radiation)
Treatment (chemotherapy, radiotherapy, autologous SCI)
INDUCTION: Patients receive vincristine IV; cisplatin IV; cyclophosphamide IV; and G-CSF SC beginning on day 3 and continuing until blood counts recover.
CONSOLIDATION (stage 4a or 4b disease only): Patients receive carboplatin IV; thiotepa IV; and etoposide IV.
AUTOLOGOUS STEM CELL INFUSION (stage 4a or 4b disease only): Patients undergo autologous stem cell infusion on day 0 and receive G-CSF SC beginning on day 1 and continuing until blood counts recover.
RADIOTHERAPY: Patients with stage 2 or 3 disease (orbital and/or regional involvement) undergo radiotherapy to sites that were initially involved beginning within 42 days after the start of course 4 of induction chemotherapy. Patients with stage 4a or 4b disease undergo radiotherapy to sites initially involved based on response beginning approximately 42 days after autologous stem cell infusion.
干预措施: Thiotepa (Drug)
Treatment (chemotherapy, radiotherapy, autologous SCI)
INDUCTION: Patients receive vincristine IV; cisplatin IV; cyclophosphamide IV; and G-CSF SC beginning on day 3 and continuing until blood counts recover.
CONSOLIDATION (stage 4a or 4b disease only): Patients receive carboplatin IV; thiotepa IV; and etoposide IV.
AUTOLOGOUS STEM CELL INFUSION (stage 4a or 4b disease only): Patients undergo autologous stem cell infusion on day 0 and receive G-CSF SC beginning on day 1 and continuing until blood counts recover.
RADIOTHERAPY: Patients with stage 2 or 3 disease (orbital and/or regional involvement) undergo radiotherapy to sites that were initially involved beginning within 42 days after the start of course 4 of induction chemotherapy. Patients with stage 4a or 4b disease undergo radiotherapy to sites initially involved based on response beginning approximately 42 days after autologous stem cell infusion.
干预措施: Vincristine Sulfate (Drug)
结局指标
主要结局
Event-free Survival (EFS)
时间窗: At 1 year
The probability of surviving patients who did not experience events at 1 year following enrollment. An event is defined as relapse, second malignancy, or death from any cause.
次要结局
- Response Rate to the Induction Phase of the Regimen(12 weeks after participant received the first dose)
- Percentage of Participants With Adverse Events as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0(Up to 30 days after completion of study treatment)