Systemic Chemotherapy and Subtenon Carboplatin, and Local Ophthalmic Therapy in Children With Intraocular Retinoblastoma
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| ClinicalTrials.gov Identifier: NCT00072384 |
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Recruitment Status :
Completed
First Posted : November 6, 2003
Results First Posted : September 19, 2018
Last Update Posted : July 30, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Intraocular Retinoblastoma | Drug: liposomal vincristine sulfate Procedure: cryosurgery Procedure: laser surgery Drug: carboplatin Drug: etoposide Biological: filgrastim | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 30 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Single Arm Trial of Systemic And Subtenon Chemotherapy For Groups C And D Intraocular Retinoblastoma |
| Actual Study Start Date : | April 16, 2007 |
| Actual Primary Completion Date : | February 1, 2013 |
| Actual Study Completion Date : | June 30, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Treatment (chemotherapy, surgery)
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.
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Drug: liposomal vincristine sulfate
Given IV
Other Names:
Procedure: cryosurgery Application of extreme cold to destroy abnormal or diseased tissue.
Other Names:
Procedure: laser surgery Surgery using a laser (instead of a scalpel) to cut tissue
Other Names:
Drug: carboplatin Given IV
Other Names:
Drug: etoposide Given IV
Other Names:
Biological: filgrastim Given subcutaneously
Other Names:
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- Group D Eyes - Treatment Failure Within One Year [ Time Frame: 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 [ Time Frame: 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.
- Event-free Survival (EFS) [ Time Frame: One year after study enrollment ]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 [ Time Frame: From date of enrollment until termination of protocol therapy assessed up to 72 weeks ]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 [ Time Frame: From the date of enrollment assessed up to 36 months ]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 [ Time Frame: From the date of enrollment assessed up to 12 months ]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.
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| Ages Eligible for Study: | up to 17 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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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:
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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
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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
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- Prior enucleation of 1 eye allowed provided the remaining eye is group C or D
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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
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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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00072384
| United States, California | |
| Children's Oncology Group | |
| Arcadia, California, United States, 91006-3776 | |
| Southern California Permanente Medical Group | |
| Downey, California, United States, 90242 | |
| Children's Hospital Los Angeles | |
| Los Angeles, California, United States, 90027 | |
| United States, Connecticut | |
| Yale University | |
| New Haven, Connecticut, United States, 06520-8032 | |
| United States, District of Columbia | |
| Lombardi Comprehensive Cancer Center at Georgetown University | |
| Washington, District of Columbia, United States, 20057 | |
| United States, Georgia | |
| Children's Healthcare of Atlanta - Egleston | |
| Atlanta, Georgia, United States, 30322 | |
| United States, Illinois | |
| University of Illinois | |
| Chicago, Illinois, United States, 60612 | |
| United States, North Carolina | |
| Duke University Medical Center | |
| Durham, North Carolina, United States, 27710 | |
| United States, Ohio | |
| Cincinnati Children's Hospital Medical Center | |
| Cincinnati, Ohio, United States, 45229 | |
| United States, Texas | |
| Baylor College of Medicine | |
| Houston, Texas, United States, 77030 | |
| M D Anderson Cancer Center | |
| Houston, Texas, United States, 77030 | |
| Principal Investigator: | Rima Jubran | Children's Oncology Group |
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00072384 |
| 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 Posted: | November 6, 2003 Key Record Dates |
| Results First Posted: | September 19, 2018 |
| Last Update Posted: | July 30, 2021 |
| Last Verified: | July 2021 |
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Retinoblastoma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Retinal Neoplasms Eye Neoplasms Neoplasms by Site Eye Diseases, Hereditary Eye Diseases Retinal Diseases |
Carboplatin Etoposide Vincristine Etoposide phosphate Antineoplastic Agents Antineoplastic Agents, Phytogenic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Tubulin Modulators Antimitotic Agents Mitosis Modulators |