NCT00335738 · CITED IN SOURCE DOCUMENTS

Vincristine, Carboplatin, and Etoposide or Observation Only in Treating Patients Who Have Undergone Surgery for Newly Diagnosed Retinoblastoma

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2021-02-18

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Event-free Survival (EFS)

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Toxicity As Assessed By the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

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outcome · POSTED

Pathological Features Present At Diagnosis - Posterior Uveal Invasion (PVI)

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outcome · POSTED

Pathological Features Present At Diagnosis - Tumor Involving the Optic Nerve Posterior to the Lamina Cribrosa (LC) as an Independent Finding

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outcome · POSTED

Pathological Features Present at Diagnosis - Scleral Invasion (SI)

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outcome · POSTED

Pathological Features Present At Diagnosis - Anterior Chamber Seeding (ACS)

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outcome · POSTED

Pathological Features Present At Diagnosis - Iris Infiltration (II)

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outcome · POSTED

Pathological Features Present At Diagnosis - Ciliary Body Infiltration (CBI)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * 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
healthy Volunteers: false
maximum Age: 6 Years
sex: ALL
std Ages: CHILD

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Drug: liposomal vincristine sulfate
Drug: carboplatin
Drug: etoposide
label
Group 1 (identified by central review as high risk)
type
EXPERIMENTAL
description
Patients undergo observation periodically for at least 5 years.
label
Group 2 (identified by central review as not high risk)
type
NO_INTERVENTION

interventions

arm Group Labels
Group 1 (identified by central review as high risk)
description
Given IV
name
liposomal vincristine sulfate
other Names
liposomal vincristine
Marqibo
vincristine liposomal
vincristine sulfate liposome injection
type
DRUG
arm Group Labels
Group 1 (identified by central review as high risk)
description
Given IV
name
carboplatin
other Names
Carboplat
CBDCA
JM-8
Paraplat
Paraplatin
type
DRUG
arm Group Labels
Group 1 (identified by central review as high risk)
description
Given IV
name
etoposide
other Names
EPEG
VP-16
VP-16-213
type
DRUG

Study design

allocation

NON_RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 331
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Event-free Survival (EFS)
time Frame
At 2 years
description
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.
measure
Overall Survival (OS)
time Frame
At 2 Years

secondary Outcomes

description
Number of patients assigned chemotherapy who experienced grade 3 or higher CTC AE toxicity.
measure
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
description
Proportion of patients who had posterior uveal invasion at enrollment.
measure
Pathological Features Present At Diagnosis - Posterior Uveal Invasion (PVI)
time Frame
At enrollment
description
Proportion of patients with tumor involving the optic nerve posterior to the lamina cribrosa as an independent.
measure
Pathological Features Present At Diagnosis - Tumor Involving the Optic Nerve Posterior to the Lamina Cribrosa (LC) as an Independent Finding
time Frame
At enrollment
description
Proportion of patients that had scleral invasion at enrollment.
measure
Pathological Features Present at Diagnosis - Scleral Invasion (SI)
time Frame
At enrollment
description
Proportion of patients who had anterior chamber seeding at enrollment.
measure
Pathological Features Present At Diagnosis - Anterior Chamber Seeding (ACS)
time Frame
At enrollment
description
Proportion of patients who had iris infiltration at enrollment.
measure
Pathological Features Present At Diagnosis - Iris Infiltration (II)
time Frame
At enrollment
description
Proportion of patients who had ciliary body infiltration at enrollment.
measure
Pathological Features Present At Diagnosis - Ciliary Body Infiltration (CBI)
time Frame
At Enrollment

Full study description

brief Summary: 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.
detailed Description: 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. 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.

Source references