Vincristine, Carboplatin, and Etoposide or Observation Only in Treating Patients Who Have Undergone Surgery for Newly Diagnosed Retinoblastoma
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|ClinicalTrials.gov Identifier: NCT00335738|
Recruitment Status : Completed
First Posted : June 12, 2006
Results First Posted : April 17, 2018
Last Update Posted : February 18, 2021
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|Condition or disease||Intervention/treatment||Phase|
|Intraocular Retinoblastoma||Drug: liposomal vincristine sulfate Drug: carboplatin Drug: etoposide||Phase 3|
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.
OUTLINE: This is a prospective, nonrandomized, multicenter study. Patients are assigned to 1 of 2 groups according to presence of high-risk histopathologic features.
GROUP 1 (high-risk features): Patients 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.
GROUP 2 (no high-risk features): Patients undergo observation periodically for at least 5 years.
GROUP 3 (no consensus regarding high risk features can be reached): Patients undergo Group 1 chemotherapy or observation according to institutional high-risk feature assessment.
After completion of study treatment, patients in group 1 are followed periodically for at least 5 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||331 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Study of Unilateral Retinoblastoma With and Without Histopathologic High-Risk Features and the Role of Adjuvant Chemotherapy|
|Study Start Date :||December 2005|
|Actual Primary Completion Date :||September 2011|
|Actual Study Completion Date :||September 30, 2020|
Experimental: 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.
Drug: liposomal vincristine sulfate
No Intervention: Group 2 (identified by central review as not high risk)
Patients undergo observation periodically for at least 5 years.
- Event-free Survival (EFS) [ Time Frame: 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) [ Time Frame: 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.
- Toxicity As Assessed By the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [ Time Frame: During planned six cycles of chemotherapy ]Number of patients assigned chemotherapy who experienced grade 3 or higher CTC AE toxicity.
- Pathological Features Present At Diagnosis - Posterior Uveal Invasion (PVI) [ Time Frame: At enrollment ]Proportion of patients who had posterior uveal invasion at enrollment.
- Pathological Features Present At Diagnosis - Tumor Involving the Optic Nerve Posterior to the Lamina Cribrosa (LC) as an Independent Finding [ Time Frame: At enrollment ]Proportion of patients with tumor involving the optic nerve posterior to the lamina cribrosa as an independent.
- Pathological Features Present at Diagnosis - Scleral Invasion (SI) [ Time Frame: At enrollment ]Proportion of patients that had scleral invasion at enrollment.
- Pathological Features Present At Diagnosis - Anterior Chamber Seeding (ACS) [ Time Frame: At enrollment ]Proportion of patients who had anterior chamber seeding at enrollment.
- Pathological Features Present At Diagnosis - Iris Infiltration (II) [ Time Frame: At enrollment ]Proportion of patients who had iris infiltration at enrollment.
- Pathological Features Present At Diagnosis - Ciliary Body Infiltration (CBI) [ Time Frame: At Enrollment ]Proportion of patients who had ciliary body infiltration at enrollment.
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|Ages Eligible for Study:||up to 6 Years (Child)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00335738
|Principal Investigator:||Murali Chintagumpala, MD||Children's Oncology Group|
|Responsible Party:||Children's Oncology Group|
|Other Study ID Numbers:||
NCI-2009-00423 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000483043 ( Other Identifier: Clinical Trials.gov )
U10CA098543 ( U.S. NIH Grant/Contract )
COG-ARET0332 ( Other Identifier: Children's Oncology Group )
|First Posted:||June 12, 2006 Key Record Dates|
|Results First Posted:||April 17, 2018|
|Last Update Posted:||February 18, 2021|
|Last Verified:||March 2018|
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Neoplasms by Histologic Type
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Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Molecular Mechanisms of Pharmacological Action