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

Primary Purpose

Intraocular Retinoblastoma

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
liposomal vincristine sulfate
carboplatin
etoposide
Sponsored by
Children's Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Intraocular Retinoblastoma

Eligibility Criteria

undefined - 6 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Birmingham
  • University of Arizona Health Sciences Center
  • Children's Oncology Group
  • Southern California Permanente Medical Group
  • Children's Hospital Los Angeles
  • Rady Children's Hospital - San Diego
  • University of California San Francisco Medical Center-Parnassus
  • Children's Hospital Colorado
  • Children's National Medical Center
  • Lombardi Comprehensive Cancer Center at Georgetown University
  • University of Miami Miller School of Medicine-Sylvester Cancer Center
  • University of Illinois
  • Childrens Memorial Hospital
  • University of Iowa Hospitals and Clinics
  • University of Kentucky
  • Kosair Children's Hospital
  • Maine Children's Cancer Program
  • Johns Hopkins University
  • Massachusetts General Hospital Cancer Center
  • Dana-Farber Cancer Institute
  • Wayne State University
  • University of Minnesota Medical Center-Fairview
  • Mayo Clinic
  • The Childrens Mercy Hospital
  • Washington University School of Medicine
  • Children's Hospital and Medical Center of Omaha
  • University of New Mexico Cancer Center
  • Brooklyn Hospital Center
  • Carolinas Medical Center
  • Duke University Medical Center
  • Cincinnati Children's Hospital Medical Center
  • Rainbow Babies and Childrens Hospital
  • Cleveland Clinic Foundation
  • Nationwide Children's Hospital
  • The Children's Medical Center of Dayton
  • Lehigh Valley Hospital - Muhlenberg
  • Children's Hospital of Philadelphia
  • Vanderbilt-Ingram Cancer Center
  • Cook Children's Medical Center
  • Baylor College of Medicine
  • M D Anderson Cancer Center
  • Covenant Children's Hospital
  • University of Texas Health Science Center at San Antonio
  • Scott and White Memorial Hospital
  • Primary Children's Medical Center
  • Childrens Hospital-King's Daughters
  • Marshfield Clinic
  • Midwest Children's Cancer Center
  • Royal Brisbane and Women's Hospital
  • Royal Children's Hospital
  • Princess Margaret Hospital for Children
  • CancerCare Manitoba
  • Hospital Sainte-Justine
  • L V Prasad Eye Institute
  • Starship Children's Hospital
  • Christchurch Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Group 1 (identified by central review as high risk)

Group 2 (identified by central review as not high risk)

Arm 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.

Patients undergo observation periodically for at least 5 years.

Outcomes

Primary Outcome Measures

Event-free Survival (EFS)
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)
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.

Secondary Outcome Measures

Toxicity As Assessed By the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Number of patients assigned chemotherapy who experienced grade 3 or higher CTC AE toxicity.
Pathological Features Present At Diagnosis - Posterior Uveal Invasion (PVI)
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
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)
Proportion of patients that had scleral invasion at enrollment.
Pathological Features Present At Diagnosis - Anterior Chamber Seeding (ACS)
Proportion of patients who had anterior chamber seeding at enrollment.
Pathological Features Present At Diagnosis - Iris Infiltration (II)
Proportion of patients who had iris infiltration at enrollment.
Pathological Features Present At Diagnosis - Ciliary Body Infiltration (CBI)
Proportion of patients who had ciliary body infiltration at enrollment.

Full Information

First Posted
June 8, 2006
Last Updated
February 16, 2021
Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00335738
Brief Title
Vincristine, Carboplatin, and Etoposide or Observation Only in Treating Patients Who Have Undergone Surgery for Newly Diagnosed Retinoblastoma
Official Title
A Study of Unilateral Retinoblastoma With and Without Histopathologic High-Risk Features and the Role of Adjuvant Chemotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
December 2005 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
September 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Intraocular Retinoblastoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
331 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1 (identified by central review as high risk)
Arm Type
Experimental
Arm 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.
Arm Title
Group 2 (identified by central review as not high risk)
Arm Type
No Intervention
Arm Description
Patients undergo observation periodically for at least 5 years.
Intervention Type
Drug
Intervention Name(s)
liposomal vincristine sulfate
Other Intervention Name(s)
liposomal vincristine, Marqibo, vincristine liposomal, vincristine sulfate liposome injection
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
carboplatin
Other Intervention Name(s)
Carboplat, CBDCA, JM-8, Paraplat, Paraplatin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
etoposide
Other Intervention Name(s)
EPEG, VP-16, VP-16-213
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Event-free Survival (EFS)
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.
Time Frame
At 2 years
Title
Overall Survival (OS)
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.
Time Frame
At 2 Years
Secondary Outcome Measure Information:
Title
Toxicity As Assessed By the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Description
Number of patients assigned chemotherapy who experienced grade 3 or higher CTC AE toxicity.
Time Frame
During planned six cycles of chemotherapy
Title
Pathological Features Present At Diagnosis - Posterior Uveal Invasion (PVI)
Description
Proportion of patients who had posterior uveal invasion at enrollment.
Time Frame
At enrollment
Title
Pathological Features Present At Diagnosis - Tumor Involving the Optic Nerve Posterior to the Lamina Cribrosa (LC) as an Independent Finding
Description
Proportion of patients with tumor involving the optic nerve posterior to the lamina cribrosa as an independent.
Time Frame
At enrollment
Title
Pathological Features Present at Diagnosis - Scleral Invasion (SI)
Description
Proportion of patients that had scleral invasion at enrollment.
Time Frame
At enrollment
Title
Pathological Features Present At Diagnosis - Anterior Chamber Seeding (ACS)
Description
Proportion of patients who had anterior chamber seeding at enrollment.
Time Frame
At enrollment
Title
Pathological Features Present At Diagnosis - Iris Infiltration (II)
Description
Proportion of patients who had iris infiltration at enrollment.
Time Frame
At enrollment
Title
Pathological Features Present At Diagnosis - Ciliary Body Infiltration (CBI)
Description
Proportion of patients who had ciliary body infiltration at enrollment.
Time Frame
At Enrollment

10. Eligibility

Sex
All
Maximum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Murali Chintagumpala, MD
Organizational Affiliation
Children's Oncology Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
University of Arizona Health Sciences Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
Children's Oncology Group
City
Arcadia
State/Province
California
ZIP/Postal Code
91006-3776
Country
United States
Facility Name
Southern California Permanente Medical Group
City
Downey
State/Province
California
ZIP/Postal Code
90242
Country
United States
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Rady Children's Hospital - San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
University of California San Francisco Medical Center-Parnassus
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Lombardi Comprehensive Cancer Center at Georgetown University
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20057
Country
United States
Facility Name
University of Miami Miller School of Medicine-Sylvester Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
University of Illinois
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Childrens Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60614
Country
United States
Facility Name
University of Iowa Hospitals and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
University of Kentucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
Kosair Children's Hospital
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Maine Children's Cancer Program
City
Scarborough
State/Province
Maine
ZIP/Postal Code
04074
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287-8936
Country
United States
Facility Name
Massachusetts General Hospital Cancer Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Wayne State University
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
University of Minnesota Medical Center-Fairview
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
The Childrens Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Children's Hospital and Medical Center of Omaha
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
University of New Mexico Cancer Center
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States
Facility Name
Brooklyn Hospital Center
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11201
Country
United States
Facility Name
Carolinas Medical Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Rainbow Babies and Childrens Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
The Children's Medical Center of Dayton
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45404
Country
United States
Facility Name
Lehigh Valley Hospital - Muhlenberg
City
Bethlehem
State/Province
Pennsylvania
ZIP/Postal Code
18017
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Cook Children's Medical Center
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Covenant Children's Hospital
City
Lubbock
State/Province
Texas
ZIP/Postal Code
79410
Country
United States
Facility Name
University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229-3900
Country
United States
Facility Name
Scott and White Memorial Hospital
City
Temple
State/Province
Texas
ZIP/Postal Code
76508
Country
United States
Facility Name
Primary Children's Medical Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States
Facility Name
Childrens Hospital-King's Daughters
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
Marshfield Clinic
City
Marshfield
State/Province
Wisconsin
ZIP/Postal Code
54449
Country
United States
Facility Name
Midwest Children's Cancer Center
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Royal Brisbane and Women's Hospital
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
Royal Children's Hospital
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
Princess Margaret Hospital for Children
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6008
Country
Australia
Facility Name
CancerCare Manitoba
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3E 0V9
Country
Canada
Facility Name
Hospital Sainte-Justine
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1C5
Country
Canada
Facility Name
L V Prasad Eye Institute
City
Hyderabad
ZIP/Postal Code
500 034
Country
India
Facility Name
Starship Children's Hospital
City
Grafton
State/Province
Auckland
ZIP/Postal Code
1145
Country
New Zealand
Facility Name
Christchurch Hospital
City
Christchurch
ZIP/Postal Code
8011
Country
New Zealand

12. IPD Sharing Statement

Links:
URL
https://nctn-data-archive.nci.nih.gov/
Description
Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive

Learn more about this trial

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

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