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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 : April 17, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Intraocular Retinoblastoma
Interventions Drug: liposomal vincristine sulfate
Drug: carboplatin
Drug: etoposide
Enrollment 331
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Group 1 (Identified by Central Review as High Risk) Group 2 (Identified by Central Review as Not High Risk)
Hide Arm/Group 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.
Period Title: Overall Study
Started 108 223
Completed 97 219
Not Completed 11 4
Reason Not Completed
Physician Decision             6             0
Withdrawal by Subject             2             0
Ineligible             3             4
Arm/Group Title Group 1 (High Risk) Group 2 (Not High Risk) Total
Hide Arm/Group Description

Patients receive liposomal vincristine sulfate IV aged based dosage (Pts < 36 mos: 0.05 mg/kg, Pts > 36 mos: 1.5 mg/m2, max dose 2 MG) given IV or infusion on day 1, carboplatin aged based dosage (Pts < 36 mos: 18.6 mg/kg Pts > 36 mos: 560 mg/m2) IV on day 1, and Etoposide aged based dosage (Pts < 36 mos: 5 mg/kg, Pts > 36 mos: 150 mg/m2) IV on days 1 and 2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

liposomal vincristine sulfate: Given IV

carboplatin: Given IV

etoposide: Given IV

Patients undergo observation periodically for at least 5 years. Total of all reporting groups
Overall Number of Baseline Participants 108 223 331
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 108 participants 223 participants 331 participants
2
(0 to 6)
1
(0 to 6)
2
(0 to 6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 108 participants 223 participants 331 participants
Female
52
  48.1%
107
  48.0%
159
  48.0%
Male
56
  51.9%
116
  52.0%
172
  52.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 108 participants 223 participants 331 participants
Hispanic or Latino
24
  22.2%
32
  14.3%
56
  16.9%
Not Hispanic or Latino
82
  75.9%
181
  81.2%
263
  79.5%
Unknown or Not Reported
2
   1.9%
10
   4.5%
12
   3.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 108 participants 223 participants 331 participants
American Indian or Alaska Native
1
   0.9%
0
   0.0%
1
   0.3%
Asian
37
  34.3%
63
  28.3%
100
  30.2%
Native Hawaiian or Other Pacific Islander
1
   0.9%
1
   0.4%
2
   0.6%
Black or African American
8
   7.4%
17
   7.6%
25
   7.6%
White
43
  39.8%
108
  48.4%
151
  45.6%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
18
  16.7%
34
  15.2%
52
  15.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 108 participants 223 participants 331 participants
United States 65 144 209
New Zealand 1 7 8
India 32 55 87
Mexico 1 0 1
Canada 3 7 10
Australia 6 8 14
Bangladesh 0 2 2
1.Primary Outcome
Title Event-free Survival (EFS)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Only eligible patients are considered in the characterization of EFS at 2 years.
Arm/Group Title Group 1 (Identified by Central Review as High Risk) Group 2 (Identified by Central Review as Not High Risk)
Hide Arm/Group 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.
Overall Number of Participants Analyzed 89 235
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Estimated Probability
0.9394
(0.8606 to 0.9743)
0.9953
(0.9671 to 0.9993)
2.Primary Outcome
Title Overall Survival (OS)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Only eligible patients are considered for this outcome measure. This is calculated as the total number of patients enrolled in each group with the number ineligible in each group subtracted as reported on the participant flow template.
Arm/Group Title Group 1 (Identified by Central Review as High Risk) Group 2 (Identified by Central Review as Not High Risk)
Hide Arm/Group 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.
Overall Number of Participants Analyzed 89 235
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Estimated Probability
0.9628
(0.8890 to 0.9878)
1
(1 to 1)
3.Secondary Outcome
Title Toxicity As Assessed By the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Hide Description Number of patients assigned chemotherapy who experienced grade 3 or higher CTC AE toxicity.
Time Frame During planned six cycles of chemotherapy
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Adverse experiences as coded using CTC AE version 4 were collected only for patients who received chemotherapy according to protocol guidelines. Of the 105 eligible patients with high risk features, ninety-three (93) were given protocol chemotherapy based on the assessment of the central pathology review, as described in section 4 of the ARET0332.
Arm/Group Title Group 1 (Identified by Central Review as High Risk)
Hide Arm/Group 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.
Overall Number of Participants Analyzed 93
Measure Type: Number
Unit of Measure: participants
19
4.Secondary Outcome
Title Pathological Features Present At Diagnosis - Posterior Uveal Invasion (PVI)
Hide Description Proportion of patients who had posterior uveal invasion at enrollment.
Time Frame At enrollment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Central review of the biological materials for this aim was available on only 313 patients. This outcome measure is calculated by combing all groups as characterized in the Patient Flow.
Arm/Group Title All Patients
Hide Arm/Group Description:
This outcome measure is calculated by combining all groups as defined in the trials record.
Overall Number of Participants Analyzed 313
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of patients with PVI
0.24
(0.19 to 0.29)
5.Secondary Outcome
Title Pathological Features Present At Diagnosis - Tumor Involving the Optic Nerve Posterior to the Lamina Cribrosa (LC) as an Independent Finding
Hide Description Proportion of patients with tumor involving the optic nerve posterior to the lamina cribrosa as an independent.
Time Frame At enrollment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Central review of the biological materials for this aim was available on only 313 patients. This outcome measure is calculated by combing all groups as characterized in the Patient Flow.
Arm/Group Title All Patients
Hide Arm/Group Description:
This outcome measure is calculated by combining all groups as defined in the trials record.
Overall Number of Participants Analyzed 313
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of patients with LC
0.16
(0.12 to 0.21)
6.Secondary Outcome
Title Pathological Features Present at Diagnosis - Scleral Invasion (SI)
Hide Description Proportion of patients that had scleral invasion at enrollment.
Time Frame At enrollment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Central review of the biological materials for this aim was available on only 313 patients. This outcome measure is calculated by combing all groups as characterized in the Patient Flow.
Arm/Group Title All Patients
Hide Arm/Group Description:
This outcome measure is calculated by combining all groups as defined in the trials record.
Overall Number of Participants Analyzed 313
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of patients with SI
0.016
(0.0052 to 0.037)
7.Secondary Outcome
Title Pathological Features Present At Diagnosis - Anterior Chamber Seeding (ACS)
Hide Description Proportion of patients who had anterior chamber seeding at enrollment.
Time Frame At enrollment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Central review of the biological materials for this aim was available on only 313 patients. This outcome measure is calculated by combing all groups as characterized in the Patient Flow.
Arm/Group Title All Patients
Hide Arm/Group Description:
This outcome measure is calculated by combining all groups as defined in the trials record.
Overall Number of Participants Analyzed 313
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of patients with ACS
0.045
(0.025 to 0.074)
8.Secondary Outcome
Title Pathological Features Present At Diagnosis - Iris Infiltration (II)
Hide Description Proportion of patients who had iris infiltration at enrollment.
Time Frame At enrollment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Central review of the biological materials for this aim was available on only 313 patients. This outcome measure is calculated by combing all groups as characterized in the Patient Flow.
Arm/Group Title All Patients
Hide Arm/Group Description:
This outcome measure is calculated by combining all groups as defined in the trials record.
Overall Number of Participants Analyzed 313
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of patients with II
0.029
(0.013 to 0.054)
9.Secondary Outcome
Title Pathological Features Present At Diagnosis - Ciliary Body Infiltration (CBI)
Hide Description Proportion of patients who had ciliary body infiltration at enrollment.
Time Frame At Enrollment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Central review of the biological materials for this aim was available on only 313 patients. This outcome measure is calculated by combing all groups as characterized in the Patient Flow.
Arm/Group Title All Patients
Hide Arm/Group Description:
This outcome measure is calculated by combining all groups as defined in the trials record.
Overall Number of Participants Analyzed 313
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of patients with CBI
0.019
(0.0071 to 0.041)
Time Frame [Not Specified]
Adverse Event Reporting Description Adverse experiences as coded using CTC AE version 4 were collected only for patients who received chemotherapy according to protocol guidelines. Of the 105 eligible patients with high risk features, ninety-three (93) were given protocol chemotherapy based on the assessment of the central pathology review, as described in section 4 of the ARET0332 protocol.
 
Arm/Group Title Group 1 (Identified by Central Review as High Risk) Group 2 (Identified by Central Review as Not High Risk)
Hide Arm/Group 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.
All-Cause Mortality
Group 1 (Identified by Central Review as High Risk) Group 2 (Identified by Central Review as Not High Risk)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/93 (0.00%)   0/0 
Show Serious Adverse Events Hide Serious Adverse Events
Group 1 (Identified by Central Review as High Risk) Group 2 (Identified by Central Review as Not High Risk)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/93 (0.00%)   0/0 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Group 1 (Identified by Central Review as High Risk) Group 2 (Identified by Central Review as Not High Risk)
Affected / at Risk (%) Affected / at Risk (%)
Total   19/93 (20.43%)   0/0 
Blood and lymphatic system disorders     
Anemia  2/93 (2.15%)  0/0 
Febrile neutropenia  9/93 (9.68%)  0/0 
Gastrointestinal disorders     
Constipation  1/93 (1.08%)  0/0 
Diarrhea  1/93 (1.08%)  0/0 
Vomiting  4/93 (4.30%)  0/0 
Immune system disorders     
Anaphylaxis  5/93 (5.38%)  0/0 
Infections and infestations     
Enterocolitis infectious  1/93 (1.08%)  0/0 
Eye infection  1/93 (1.08%)  0/0 
Infections and infestations - Other, specify  2/93 (2.15%)  0/0 
Otitis media  1/93 (1.08%)  0/0 
Investigations     
Alanine aminotransferase increased  1/93 (1.08%)  0/0 
Aspartate aminotransferase increased  1/93 (1.08%)  0/0 
Neutrophil count decreased  6/93 (6.45%)  0/0 
Platelet count decreased  4/93 (4.30%)  0/0 
Metabolism and nutrition disorders     
Anorexia  1/93 (1.08%)  0/0 
Dehydration  2/93 (2.15%)  0/0 
Nervous system disorders     
Headache  1/93 (1.08%)  0/0 
Skin and subcutaneous tissue disorders     
Rash maculo-papular  1/93 (1.08%)  0/0 
The COG SDC reviewed the NLM notification related to ct.gov AE/SAE reporting. The information in ‘Additional Description’ is accurate with respect to data supplied to ct.gov.COG plans to submit data AE/SAE data consistent with the text in this field.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Must obtain prior Sponsor approval.
Results Point of Contact
Name/Title: Results Reporting Coordinator
Organization: Children's Oncology Group
Phone: 352-273-0567
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00335738     History of Changes
Other Study ID Numbers: ARET0332
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 Submitted: June 8, 2006
First Posted: June 12, 2006
Results First Submitted: December 2, 2015
Results First Posted: April 17, 2018
Last Update Posted: April 17, 2018