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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

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.

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

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
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
Study Start Date : April 2007
Actual Primary Completion Date : February 2013
Actual Study Completion Date : September 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Drug: liposomal vincristine sulfate
Given IV
Other Names:
  • liposomal vincristine
  • Marqibo
  • vincristine liposomal
  • vincristine sulfate liposome injection

Procedure: cryosurgery
Application of extreme cold to destroy abnormal or diseased tissue.
Other Names:
  • cryoablation
  • cryosurgical ablation

Procedure: laser surgery
Surgery using a laser (instead of a scalpel) to cut tissue
Other Names:
  • conventional laser therapy
  • laser therapy, conventional
  • surgery, laser

Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin

Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213

Biological: filgrastim
Given subcutaneously
Other Names:
  • G-CSF
  • Neupogen




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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

  4. 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
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

Information from the National Library of Medicine

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


Locations
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
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: Rima Jubran Children's Oncology Group

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 Posted: November 6, 2003    Key Record Dates
Results First Posted: September 19, 2018
Last Update Posted: September 19, 2018
Last Verified: August 2018

Additional relevant MeSH terms:
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
Retinal Diseases
Etoposide phosphate
Carboplatin
Etoposide
Vincristine
Lenograstim
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs