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

Primary Purpose

Intraocular Retinoblastoma

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
liposomal vincristine sulfate
cryosurgery
laser surgery
carboplatin
etoposide
filgrastim
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 - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Diagnosis of bilateral retinoblastoma with at least 1 eye group C or D intraocular retinoblastoma by ophthalmologic examination, defined by the International Classification System for Intraocular Retinoblastoma as the following: 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 Prior enucleation of 1 eye allowed provided the remaining eye is group C or D No tumor present on histologic examination at the cut end of the optic nerve on any eye enucleated prior to study entry Evidence of choroidal and/or optic nerve invasion past the lumina cribrosa is allowed No extraocular retinoblastoma clinically or by MRI of brain and orbits with and without gadolinium or CT scan with and without contrast of brain and orbits No evidence of systemic metastases by bone marrow, lumbar puncture, bone scan, and/or any other additional test Performance status - Karnofsky 50-100% (over 16 years of age) Performance status - Lansky 50-100% (16 and under) Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age AST and ALT < 2.5 times ULN for age 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/1.73m^2 Not pregnant or nursing Fertile patients must use effective contraception Negative pregnancy test in postmenarchal females No prior chemotherapy No other concurrent chemotherapy No prior radiotherapy No other concurrent radiotherapy

Sites / Locations

  • Children's Oncology Group
  • Southern California Permanente Medical Group
  • Children's Hospital Los Angeles
  • Yale University
  • Lombardi Comprehensive Cancer Center at Georgetown University
  • Children's Healthcare of Atlanta - Egleston
  • University of Illinois
  • Duke University Medical Center
  • Cincinnati Children's Hospital Medical Center
  • Baylor College of Medicine
  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (chemotherapy, surgery)

Arm 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.

Outcomes

Primary Outcome Measures

Group D Eyes - Treatment Failure Within One Year
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.
Group C Eyes - Treatment Failure Within One Year
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.

Secondary Outcome Measures

Event-free Survival (EFS)
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.
Toxicity Associated With Chemotherapy
The number of patients that experience CTC Version 4 grade 3 or higher toxicities of any kind.
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
Sites of disease recurrence for Group C and Group D eyes where treatment failure was detected
Patterns of Treatment Failure vs. no Treatment Failure for Group C Eyes and Group D Eyes According to Initial Sites of Involvement
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.

Full Information

First Posted
November 4, 2003
Last Updated
July 12, 2021
Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00072384
Brief Title
Systemic Chemotherapy and Subtenon Carboplatin, and Local Ophthalmic Therapy in Children With Intraocular Retinoblastoma
Official Title
A Single Arm Trial of Systemic And Subtenon Chemotherapy For Groups C And D Intraocular Retinoblastoma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
April 16, 2007 (Actual)
Primary Completion Date
February 1, 2013 (Actual)
Study Completion Date
June 30, 2021 (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
Phase III trial to determine the effectiveness of combining systemic chemotherapy and subtenon carboplatin with ophthalmic therapy in treating children who have intraocular retinoblastoma. Drugs used in chemotherapy, such as vincristine, carboplatin, and etoposide, work in different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether systemic chemotherapy and subtenon (under the conjunctiva of the eye) carboplatin combined with ophthalmic therapy is effective in treating intraocular (within the eyeball) retinoblastoma.
Detailed Description
PRIMARY OBJECTIVES: I. Determine the event-free survival at 12 months of pediatric patients' eyes with group D intraocular retinoblastoma treated with systemic chemotherapy comprising vincristine, carboplatin, and etoposide, subtenon carboplatin, and local ophthalmic therapy. (Event defined for each eye individually as needed for nonprotocol therapy including nonprotocol chemotherapy, enucleation or any external-beam radiation) SECONDARY OBJECTIVES: I. Determine the event-free survival at 12 months of pediatric patients' eyes with group C retinoblastoma treated with systemic chemotherapy comprising carboplatin, etoposide, vincristine, subtenon carboplatin, and local ophthalmic therapy. II. Determine the acute and long-term toxic effects of these regimens in these patients, including visual outcome and incidence of secondary malignancies. III. Determine the patterns of failure in patients treated with these regimens, in terms of vitreous vs retinal vs both as sites of recurrence. IV. Determine predictors of failure including findings at the on study examination under anesthesia and response status after six courses of chemotherapy. V. Determine the percentage of group C and D eyes separately that can be preserved without enucleation after failing protocol therapy. OUTLINE: This is a multicenter study. Patients receive vincristine 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 1 prior 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 and/or cryotherapy on day 1. Patients are followed with ophthalmology exams every 4-12 weeks until 3 years of age, every 6 months until 5 years of age, and then annually for up to 10 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
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (chemotherapy, surgery)
Arm Type
Experimental
Arm 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.
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
Procedure
Intervention Name(s)
cryosurgery
Other Intervention Name(s)
cryoablation, cryosurgical ablation
Intervention Description
Application of extreme cold to destroy abnormal or diseased tissue.
Intervention Type
Procedure
Intervention Name(s)
laser surgery
Other Intervention Name(s)
conventional laser therapy, laser therapy, conventional, surgery, laser
Intervention Description
Surgery using a laser (instead of a scalpel) to cut tissue
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
Intervention Type
Biological
Intervention Name(s)
filgrastim
Other Intervention Name(s)
G-CSF, Neupogen
Intervention Description
Given subcutaneously
Primary Outcome Measure Information:
Title
Group D Eyes - Treatment Failure Within One Year
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
Title
Group C Eyes - Treatment Failure Within One Year
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
Secondary Outcome Measure Information:
Title
Event-free Survival (EFS)
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
Title
Toxicity Associated With Chemotherapy
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
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
Description
Sites of disease recurrence for Group C and Group D eyes where treatment failure was detected
Time Frame
From the date of enrollment assessed up to 36 months
Title
Patterns of Treatment Failure vs. no Treatment Failure for Group C Eyes and Group D Eyes According to Initial Sites of Involvement
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

10. Eligibility

Sex
All
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of bilateral retinoblastoma with at least 1 eye group C or D intraocular retinoblastoma by ophthalmologic examination, defined by the International Classification System for Intraocular Retinoblastoma as the following: 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 Prior enucleation of 1 eye allowed provided the remaining eye is group C or D No tumor present on histologic examination at the cut end of the optic nerve on any eye enucleated prior to study entry Evidence of choroidal and/or optic nerve invasion past the lumina cribrosa is allowed No extraocular retinoblastoma clinically or by MRI of brain and orbits with and without gadolinium or CT scan with and without contrast of brain and orbits No evidence of systemic metastases by bone marrow, lumbar puncture, bone scan, and/or any other additional test Performance status - Karnofsky 50-100% (over 16 years of age) Performance status - Lansky 50-100% (16 and under) Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age AST and ALT < 2.5 times ULN for age 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/1.73m^2 Not pregnant or nursing Fertile patients must use effective contraception Negative pregnancy test in postmenarchal females No prior chemotherapy No other concurrent chemotherapy No prior radiotherapy No other concurrent radiotherapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rima Jubran
Organizational Affiliation
Children's Oncology Group
Official's Role
Principal Investigator
Facility Information:
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
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520-8032
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
Children's Healthcare of Atlanta - Egleston
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Illinois
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
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
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

12. IPD Sharing Statement

Learn more about this trial

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

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