Adjuvant Chemotherapy for High-risk Retinoblastoma After Enucleation

Study Overview
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Brief Summary
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The purpose of this study is to determine whether 3 cycles of chemotherapy(CEV) is not inferior to 6 cycles of chemotherapy(CEV) in the treatment of Stage I enucleated retinoblastoma.

Detailed Description
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This study will be a phase Ⅲ open label interventional case series. Patients with unilateral Stage I enucleated retinoblastoma will be randomized to receive chemotherapy(CEV) of 3 cycles or 6 cycles every 21 days. Patients will be followed for 60 months.

Official Title
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Three Cycles Versus Six Cycles of Adjuvant Chemotherapy for the Patients With High-risk Retinoblastoma After Enucleation: Prospective Randomized Control Study

Conditions
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Retinoblastoma

Intervention / Treatment
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* Drug: 3 cycles chemotherapy
* Drug: 6 cycles chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to provide written informed consent and comply with study assessments for the full duration of the study. Definite pathology signs of retinoblastoma, Stage I base on International Retinoblastoma Staging System. Received enucleation in the study eye. Monocular retinoblastoma. Exclusion Criteria: Any previous disease in the study eye. Previous participation in any studies of investigational drugs within 1 month preceding Day 0 (excluding vitamins and minerals). History of chemical intervention for retinoblastoma in the study eye.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3 cycles chemotherapy<br>Chemotherapy: vincristine 0.05 mg/kg (or 1.5 mg/m2 for children ≥ 3 years of age) on Day 1, carboplatin 18.6 mg/kg (or 560 mg/m2 for children ≥ 3 years of age) on Day 1, etoposide 5.0 mg/kg/day (or 150 mg/ m2 for children ≥ 3 years of age) on Days 1 and 2 and 2. Cycles were repeated every 21 days for three cycles. | Drug: 3 cycles chemotherapy<br>* Chemotherapy: vincristine 0.05 mg/kg (or 1.5 mg/m2 for children ≥ 3 years of age) on Day 1, carboplatin 18.6 mg/kg (or 560 mg/m2 for children ≥ 3 years of age) on Day 1, etoposide 5.0 mg/kg/day (or 150 mg/ m2 for children ≥ 3 years of age) on Days 1 and 2 and 2. Cycles were repeated every 21 days for three cycles.<br>* Other names: vincristine, carboplatin, etoposide.;|
| Active Comparator: 6 cycles chemotherapy<br>Chemotherapy: vincristine 0.05 mg/kg (or 1.5 mg/m2 for children ≥ 3 years of age) on Day 1, carboplatin 18.6 mg/kg (or 560 mg/m2 for children ≥ 3 years of age) on Day 1, etoposide 5.0 mg/kg/day (or 150 mg/ m2 for children ≥ 3 years of age) on Days 1 and 2 and 2. Cycles were repeated every 21 days for six cycles. | Drug: 6 cycles chemotherapy<br>* Chemotherapy: vincristine 0.05 mg/kg (or 1.5 mg/m2 for children ≥ 3 years of age) on Day 1, carboplatin 18.6 mg/kg (or 560 mg/m2 for children ≥ 3 years of age) on Day 1, etoposide 5.0 mg/kg/day (or 150 mg/ m2 for children ≥ 3 years of age) on Days 1 and 2 and 2. Cycles were repeated every 21 days for six cycles.<br>* Other names: vincristine, carboplatin, etoposide.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease-free survival | measure the disease-free survival rate for the two groups at five years | five years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | time from randomization to death as a result of any cause at five years | five years | 
| safety: side effects of chemotherapy in the Treatment of Retinoblastoma | Number of participants with side effects (systemic check-up, audio acuity, ect)before each treatment, at 1,3,6,9,12,18,24,30,36,42,48,54,60 months after the treatment. | five years | 
| quality of life (PedsQL4.0 scale) in the Treatment of Retinoblastoma | quality of life (PedsQL4.0 scale) before each treatment, at 1,3,6,9,12,18,24,30,36,42,48,54,60 months after the treatment. PedsQL 4.0 questionnaire has two modules (reported by parents and children) with 23 items encompassing the physical domains (8 items), emotional (5 items), social (5 items) and school (5 items). A five scores scale is used, after being asked, ''How much, in the last month, your child has had problems with'' (0 = never a problem; 1 = almost never a problem; 2 = sometimes a problem; 3 = is often a problem and 4 = almost always a problem). The items are reverse-score and linearly transformed to a scale from 0 to 100 (0=100, 1=75, 2=50, 3=25, 4 = 0). So high scores indicate better QoL. | five years | 
| economic burden due to chemotherapy | All costs, including direct cost and indirect cost, are expressed in Chinese YUAN. Direct costs include the average cost of systemic chemotherapy, operation, supportive treatment, and examination. Indirect costs include accommodation, transportation, diet, and lost income of parents. | during chemotherapy (9 weeks for 3-cycle group, and 18 weeks for 6-cycle group) |