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Systemic Vincristine, Carboplatin, and Etoposide, Subtenon Carboplatin, and Local Ophthalmic Therapy in Treating Children With Intraocular Retinoblastoma
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), November 2009
First Received: November 4, 2003   Last Updated: November 19, 2009   History of Changes
Sponsor: Children's Oncology Group
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00072384
  Purpose

RATIONALE: 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.

PURPOSE: Phase III trial to determine the effectiveness of combining systemic chemotherapy and subtenon carboplatin with ophthalmic therapy in treating children who have intraocular retinoblastoma.


Condition Intervention Phase
Retinoblastoma
Biological: filgrastim
Drug: carboplatin
Drug: etoposide
Drug: vincristine sulfate
Procedure: cryosurgery
Procedure: laser surgery
Phase III

Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: A Single Arm Trial of Systemic And Subtenon Chemotherapy For Groups C And D Intraocular Retinoblastoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Event-free survival at 12 months of pediatric patients' eyes with intraocular group C and/or D retinoblastoma [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Acute and long-term toxic effects [ Designated as safety issue: Yes ]
  • Patterns of failure [ Designated as safety issue: No ]
  • Predictors of failure [ Designated as safety issue: No ]
  • Percentage of preservation without enucleation after failed treatment [ Designated as safety issue: No ]

Estimated Enrollment: 69
Study Start Date: April 2007
Estimated Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • 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

  • 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.
  • Determine the acute and long-term toxic effects of these regimens in these patients, including visual outcome and incidence of secondary malignancies.
  • Determine the patterns of failure in patients treated with these regimens, in terms of vitreous vs retinal vs both as sites of recurrence.
  • Determine predictors of failure including findings at the on study examination under anesthesia and response status after six courses of chemotherapy.
  • 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.

PROJECTED ACCRUAL: A total of 69 patients will be accrued for this study within 3 years.

  Eligibility

Ages Eligible for Study:   up to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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 cribosa 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

PATIENT CHARACTERISTICS:

Age

  • Under 18

Performance status

  • Karnofsky 50-100% (over 16 years of age)
  • Lansky 50-100% (16 and under)

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
  • AST and ALT < 2.5 times ULN for age

Renal

  • 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]) OR
  • Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min/1.73m^2

Other

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • Negative pregnancy test in postmenarchal females

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior chemotherapy
  • No other concurrent chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior radiotherapy
  • No other concurrent radiotherapy

Surgery

  • See Disease Characteristics
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00072384

Locations
United States, California
Childrens Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
Contact: Leo Mascarenhas     323-361-2529        
United States, Florida
University of Miami Sylvester Comprehensive Cancer Center - Miami Recruiting
Miami, Florida, United States, 33136
Contact: University of Miami Sylvester Comprehensive Cancer Center Clin     866-574-5124     Sylvester@emergingmed.com    
United States, Georgia
Winship Cancer Institute of Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Howard M. Katzenstein     404-785-0853        
United States, Illinois
Children's Memorial Hospital - Chicago Recruiting
Chicago, Illinois, United States, 60614
Contact: Stewart Goldman     773-880-3270        
University of Illinois Cancer Center Recruiting
Chicago, Illinois, United States, 60612-7243
Contact: Clinical Trial Office - University of Illinois Cancer Center     312-355-3046        
United States, North Carolina
Duke Comprehensive Cancer Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Clinical Trials Office - Duke Comprehensive Cancer Center     888-275-3853        
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229-3039
Contact: Clinical Trials Office - Cincinnati Children's Hospital Medica     513-636-2799        
United States, Texas
Baylor University Medical Center - Houston Recruiting
Houston, Texas, United States, 77030-2399
Contact: Patrick A. Thompson     832-824-4029        
M. D. Anderson Cancer Center at University of Texas Recruiting
Houston, Texas, United States, 77030-4009
Contact: Clinical Trials Office - M. D. Anderson Cancer Center at the U     713-792-3245        
United States, Washington
Children's Hospital and Regional Medical Center - Seattle Recruiting
Seattle, Washington, United States, 98105
Contact: Julie R. Park     206-987-2106        
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Rima Jubran, MD Children's Hospital Los Angeles
Investigator: Timothy G. Murray, MD University of Miami Sylvester Comprehensive Cancer Center - Miami
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Oncology Group - Group Chair Office ( Gregory H. Reaman )
Study ID Numbers: CDR0000339627, COG-ARET0231
Study First Received: November 4, 2003
Last Updated: November 19, 2009
ClinicalTrials.gov Identifier: NCT00072384     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
intraocular retinoblastoma

Additional relevant MeSH terms:
Retinal Neoplasms
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Neoplasms, Nerve Tissue
Retinoblastoma
Etoposide phosphate
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Therapeutic Uses
Etoposide
Retinal Diseases
Neoplasms by Histologic Type
Eye Neoplasms
Eye Diseases
Mitosis Modulators
Vincristine
Carboplatin
Antimitotic Agents
Pharmacologic Actions
Neuroectodermal Tumors
Neoplasms
Tubulin Modulators
Neoplasms, Neuroepithelial
Antineoplastic Agents, Phytogenic
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 30, 2009