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Systemic Chemotherapy and Subtenon Carboplatin, and Local Ophthalmic Therapy in Children With Intraocular Retinoblastoma

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ClinicalTrials.gov Identifier: NCT00072384
Recruitment Status : Terminated
First Posted : November 6, 2003
Results First Posted : September 19, 2018
Last Update Posted : September 19, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Intraocular Retinoblastoma
Interventions Drug: liposomal vincristine sulfate
Procedure: cryosurgery
Procedure: laser surgery
Drug: carboplatin
Drug: etoposide
Biological: filgrastim
Enrollment 30
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment (Chemotherapy, Surgery)
Hide Arm/Group Description

Patients receive liposomal vincristine sulfate IV over 1 minute on day 1 and carboplatin IV over 1 hour and etoposide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 3 and continuing until blood counts recover. Patients receive subtenon carboplatin to each group C or D eye on day 0 or 1prior of courses 2-4 only. Treatment repeats every 28 days for 6 courses in the absence of occurrence of extraocular retinoblastoma or a second malignancy. Beginning with course 3 of systemic chemotherapy, patients undergo local ophthalmic therapy comprising local laser surgery and/or cryosurgery on day 1.

liposomal vincristine sulfate: Given IV

cryosurgery: Application of extreme cold to destroy abnormal or diseased tissue.

laser surgery: Surgery using a laser (instead of a scalpel) to cut tissue

carboplatin: Given IV

etoposide: Given IV

filgrastim: Given subcutaneously

Period Title: Overall Study
Started 30
Completed 21
Not Completed 9
Reason Not Completed
Physician Decision             1
Ineligible             8
Arm/Group Title Treatment (Chemotherapy, Surgery)
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Patients receive liposomal vincristine sulfate IV over 1 minute on day 1 and carboplatin IV over 1 hour and etoposide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 3 and continuing until blood counts recover. Patients receive subtenon carboplatin to each group C or D eye on day 0 or 1prior of courses 2-4 only. Treatment repeats every 28 days for 6 courses in the absence of occurrence of extraocular retinoblastoma or a second malignancy. Beginning with course 3 of systemic chemotherapy, patients undergo local ophthalmic therapy comprising local laser surgery and/or cryosurgery on day 1.

liposomal vincristine sulfate: Given IV

cryosurgery: Application of extreme cold to destroy abnormal or diseased tissue.

laser surgery: Surgery using a laser (instead of a scalpel) to cut tissue

carboplatin: Given IV

etoposide: Given IV

filgrastim: Given subcutaneously

Overall Number of Baseline Participants 30
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Months
Number Analyzed 30 participants
7.5
(1 to 52)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Female
16
  53.3%
Male
14
  46.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Hispanic or Latino
11
  36.7%
Not Hispanic or Latino
19
  63.3%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
American Indian or Alaska Native
0
   0.0%
Asian
2
   6.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
7
  23.3%
White
12
  40.0%
More than one race
0
   0.0%
Unknown or Not Reported
9
  30.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 30 participants
30
1.Primary Outcome
Title Group D Eyes - Treatment Failure Within One Year
Hide Description Each Group D eye will be classified as experiencing failure within one year after start of treatment: yes or no. The method of Rosner et al. (Biometrics v. 38, 105-114, 1982) will be used to model possible dependence between eyes from the same patient. The point estimate of the probability of treatment failure is reported as the "Mean" measure type.
Time Frame One year
Hide Outcome Measure Data
Hide Analysis Population Description
Twenty eligible patients had at least one Group D eye to contribute to the analysis. A total of 25 Group D eyes were available for analysis.
Arm/Group Title Treatment (Chemotherapy, Surgery)
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Patients receive liposomal vincristine sulfate IV over 1 minute on day 1 and carboplatin IV over 1 hour and etoposide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 3 and continuing until blood counts recover. Patients receive subtenon carboplatin to each group C or D eye on day 0 or 1prior of courses 2-4 only. Treatment repeats every 28 days for 6 courses in the absence of occurrence of extraocular retinoblastoma or a second malignancy. Beginning with course 3 of systemic chemotherapy, patients undergo local ophthalmic therapy comprising local laser surgery and/or cryosurgery on day 1.

liposomal vincristine sulfate: Given IV

cryosurgery: Application of extreme cold to destroy abnormal or diseased tissue.

laser surgery: Surgery using a laser (instead of a scalpel) to cut tissue

carboplatin: Given IV

etoposide: Given IV

filgrastim: Given subcutaneously

Overall Number of Participants Analyzed 20
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
25
Mean (Standard Deviation)
Unit of Measure: Probability of treatment failure
0.52  (0.102299)
2.Primary Outcome
Title Group C Eyes - Treatment Failure Within One Year
Hide Description Each Group C eye will be classified as experiencing failure within one year after start of treatment: yes or no. The method of Rosner et al. (Biometrics v. 38, 105-114, 1982) will be used to model possible dependence between eyes from the same patient. The point estimate of the probability of treatment failure is reported as the "Mean" measure type.
Time Frame One year
Hide Outcome Measure Data
Hide Analysis Population Description
Four eligible patients had at least one Group C eye to contribute to the analysis
Arm/Group Title Treatment (Chemotherapy, Surgery)
Hide Arm/Group Description:

Patients receive liposomal vincristine sulfate IV over 1 minute on day 1 and carboplatin IV over 1 hour and etoposide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 3 and continuing until blood counts recover. Patients receive subtenon carboplatin to each group C or D eye on day 0 or 1prior of courses 2-4 only. Treatment repeats every 28 days for 6 courses in the absence of occurrence of extraocular retinoblastoma or a second malignancy. Beginning with course 3 of systemic chemotherapy, patients undergo local ophthalmic therapy comprising local laser surgery and/or cryosurgery on day 1.

liposomal vincristine sulfate: Given IV

cryosurgery: Application of extreme cold to destroy abnormal or diseased tissue.

laser surgery: Surgery using a laser (instead of a scalpel) to cut tissue

carboplatin: Given IV

etoposide: Given IV

filgrastim: Given subcutaneously

Overall Number of Participants Analyzed 4
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
4
Mean (Standard Deviation)
Unit of Measure: Probability of treatment failure
0.25  (0.217)
3.Secondary Outcome
Title Event-free Survival (EFS)
Hide Description Proportion of patients event free at 1 year following enrollment. Event free survival time is computed as the time to study entry until disease relapse/progression, secondary malignancy, or death.
Time Frame One year after study enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
22 eligible patients were considered for this endpoint.
Arm/Group Title Treatment (Chemotherapy, Surgery)
Hide Arm/Group Description:

Patients receive liposomal vincristine sulfate IV over 1 minute on day 1 and carboplatin IV over 1 hour and etoposide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 3 and continuing until blood counts recover. Patients receive subtenon carboplatin to each group C or D eye on day 0 or 1prior of courses 2-4 only. Treatment repeats every 28 days for 6 courses in the absence of occurrence of extraocular retinoblastoma or a second malignancy. Beginning with course 3 of systemic chemotherapy, patients undergo local ophthalmic therapy comprising local laser surgery and/or cryosurgery on day 1.

liposomal vincristine sulfate: Given IV

cryosurgery: Application of extreme cold to destroy abnormal or diseased tissue.

laser surgery: Surgery using a laser (instead of a scalpel) to cut tissue

carboplatin: Given IV

etoposide: Given IV

filgrastim: Given subcutaneously

Overall Number of Participants Analyzed 22
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage probability
45.45
(24.44 to 64.33)
4.Secondary Outcome
Title Toxicity Associated With Chemotherapy
Hide Description The number of patients that experience CTC Version 4 grade 3 or higher toxicities of any kind.
Time Frame From date of enrollment until termination of protocol therapy assessed up to 72 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
22 eligible patients were evaluable for the occurrence of grade 3 or higher toxicity of any kind.
Arm/Group Title Treatment (Chemotherapy, Surgery)
Hide Arm/Group Description:

Patients receive liposomal vincristine sulfate IV over 1 minute on day 1 and carboplatin IV over 1 hour and etoposide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 3 and continuing until blood counts recover. Patients receive subtenon carboplatin to each group C or D eye on day 0 or 1prior of courses 2-4 only. Treatment repeats every 28 days for 6 courses in the absence of occurrence of extraocular retinoblastoma or a second malignancy. Beginning with course 3 of systemic chemotherapy, patients undergo local ophthalmic therapy comprising local laser surgery and/or cryosurgery on day 1.

liposomal vincristine sulfate: Given IV

cryosurgery: Application of extreme cold to destroy abnormal or diseased tissue.

laser surgery: Surgery using a laser (instead of a scalpel) to cut tissue

carboplatin: Given IV

etoposide: Given IV

filgrastim: Given subcutaneously

Overall Number of Participants Analyzed 22
Measure Type: Number
Unit of Measure: Patients
10
5.Secondary Outcome
Title Patterns of Failure for Group C and Group D in Terms of Vitreous vs Patterns of Failure for Group C and Group D in Terms of Vitreous vs Retinal vs Both as Sites of Recurrence
Time Frame From the date of enrollment assessed up to 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
1 patient had at least one Group C eye and 11 patients had at least one Group D eye that experienced treatment failure. There were a total of 13 Group D eyes that experienced treatment failure.
Arm/Group Title Group C Eyes Group D Eyes
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Group C: Discrete localized disease with minimal subretinal and/or vitreous seeding

  • Subretinal fluid, without prior or concurrent seeding, involving ≤ one quarter of the retina
  • Local fine vitreous seeding may be present close to discrete tumor
  • Local subretinal seeding < 3 mm from tumor

Group D: Diffuse disease with significant vitreous and/or subretinal seeding

  • Tumor(s) may be massive or diffuse
  • Subretinal fluid, without prior or concurrent seeding, involving up to total retinal detachment
  • Diffuse or massive vitreous disease may include "greasy" seeds or avascular tumor masses
  • Diffuse subretinal seeding may include subretinal plaques or tumor nodules
Overall Number of Participants Analyzed 1 11
Measure Type: Number
Unit of Measure: Eyes
Retinal seeding and vitreal seeding 0 1
Retinal seeding but no vitreal seeding 1 7
Vitreal seeding but no retinal seeding 0 1
Neither retinal seeding nor vitreal seeding 0 4
6.Secondary Outcome
Title Patterns of Treatment Failure vs. no Treatment Failure for Group C Eyes and Group D Eyes According to Initial Sites of Involvement
Hide Description The association between the probability of experiencing treatment failure vs. no failure in a C eye and the presence of subretinal seeding (SRS), subretinal fluid (SRF), or vitreal seeding (VS) at the on study ophthalmological examination under anesthesia. The association between the probability of experiencing treatment failure vs. no failure in a D eye and the presence of subretinal seeding (SRS), subretinal fluid (SRF), or vitreal seeding (VS) at the on study ophthalmological examination under anesthesia.
Time Frame From the date of enrollment assessed up to 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
According to the initial sites of involvement, 4 patients were analyzed in Group C eyes and 20 patients were analyzed for Group D eyes
Arm/Group Title Group C Eyes Group D Eyes
Hide Arm/Group Description:

Group C: Discrete localized disease with minimal subretinal and/or vitreous seeding

  • Subretinal fluid, without prior or concurrent seeding, involving ≤ one quarter of the retina
  • Local fine vitreous seeding may be present close to discrete tumor
  • Local subretinal seeding < 3 mm from tumor

Group D: Diffuse disease with significant vitreous and/or subretinal seeding

  • Tumor(s) may be massive or diffuse
  • Subretinal fluid, without prior or concurrent seeding, involving up to total retinal detachment
  • Diffuse or massive vitreous disease may include "greasy" seeds or avascular tumor masses
  • Diffuse subretinal seeding may include subretinal plaques or tumor nodules
Overall Number of Participants Analyzed 4 20
Measure Type: Number
Unit of Measure: Eyes
Treatment failure- SRS, SRF, VS 0 3
Treatment failure- SRS; no SRF; no VS 0 0
Treatment failure- SRS and SRF; no VS 0 3
Treatment failure- SRS and VS; no SRF 0 0
Treatment failure- SRF; no SRS; no VS 1 2
Treatment failure- SRF and VS; no SRS 0 3
Treatment failure- VS; no SRS; no SRF 0 2
Treatment failure- No SRS; no VS; no SRF 0 0
No treatment failure- SRS, SRF, VS 0 2
No treatment failure- SRS; no SRF; no VS 0 1
No treatment failure- SRS and SRF; no VS 0 2
No treatment failure- SRS and VS; no SRF 0 2
No treatment failure- SRF; no SRS; no VS 1 2
No treatment failure- SRF and VS; no SRS 0 0
No treatment failure- VS; no SRS; no SRF 1 2
No treatment failure- No SRS; no VS; no SRF 1 1
Time Frame [Not Specified]
Adverse Event Reporting Description SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Note that while the participant flow demonstrates that 21 completed all cycles of therapy, one additional patient completed fewer than 6 cycles of therapy. The AE profiles are calculated on a per-person basis for the time during which the patient was on therapy.
 
Arm/Group Title Treatment (Chemotherapy, Surgery)
Hide Arm/Group Description

Patients receive liposomal vincristine sulfate IV over 1 minute on day 1 and carboplatin IV over 1 hour and etoposide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 3 and continuing until blood counts recover. Patients receive subtenon carboplatin to each group C or D eye on day 0 or 1prior of courses 2-4 only. Treatment repeats every 28 days for 6 courses in the absence of occurrence of extraocular retinoblastoma or a second malignancy. Beginning with course 3 of systemic chemotherapy, patients undergo local ophthalmic therapy comprising local laser surgery and/or cryosurgery on day 1.

liposomal vincristine sulfate: Given IV

cryosurgery: Application of extreme cold to destroy abnormal or diseased tissue.

laser surgery: Surgery using a laser (instead of a scalpel) to cut tissue

carboplatin: Given IV

etoposide: Given IV

filgrastim: Given subcutaneously

All-Cause Mortality
Treatment (Chemotherapy, Surgery)
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Treatment (Chemotherapy, Surgery)
Affected / at Risk (%)
Total   0/22 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Treatment (Chemotherapy, Surgery)
Affected / at Risk (%)
Total   18/22 (81.82%) 
Blood and lymphatic system disorders   
Febrile neutropenia  1/22 (4.55%) 
Ear and labyrinth disorders   
Hearing impaired  2/22 (9.09%) 
Middle ear inflammation  1/22 (4.55%) 
Eye disorders   
Eye disorders - Other, specify  2/22 (9.09%) 
Infections and infestations   
Anorectal infection  1/22 (4.55%) 
Bladder infection  1/22 (4.55%) 
Device related infection  1/22 (4.55%) 
Eye infection  1/22 (4.55%) 
Infections and infestations - Other, specify  2/22 (9.09%) 
Lung infection  1/22 (4.55%) 
Investigations   
Neutrophil count decreased  3/22 (13.64%) 
Platelet count decreased  1/22 (4.55%) 
Skin and subcutaneous tissue disorders   
Skin induration  1/22 (4.55%) 
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: 626-447-0064
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00072384     History of Changes
Other Study ID Numbers: ARET0231
NCI-2009-00420 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000339627 ( Other Identifier: Clinical Trials.gov )
COG-ARET0231 ( Other Identifier: Children's Oncology Group )
U10CA098543 ( U.S. NIH Grant/Contract )
First Submitted: November 4, 2003
First Posted: November 6, 2003
Results First Submitted: November 25, 2015
Results First Posted: September 19, 2018
Last Update Posted: September 19, 2018