Systemic Vincristine, Carboplatin, and Etoposide, Subtenon Carboplatin, and Local Ophthalmic Therapy in Treating Children With Intraocular Retinoblastoma - Full Text View

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:	Masking: Open Label Primary Purpose: Treatment
Official Title:	A Single Arm Trial of Systemic And Subtenon Chemotherapy For Groups C And D Intraocular Retinoblastoma

Resource links provided by NLM:

Genetics Home Reference related topics: retinoblastoma

MedlinePlus related topics: Cancer

Drug Information available for: Vincristine Etoposide Carboplatin Etoposide phosphate Filgrastim Lenograstim Granulocyte colony-stimulating factor Vincristine sulfate

U.S. FDA Resources

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 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

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
Southern California Permanente Medical Group
Downey, California, United States, 90027
Childrens Hospital Los Angeles
Los Angeles, California, United States, 90027
United States, Connecticut
Yale Cancer Center
New Haven, Connecticut, United States, 06520-8028
United States, Delaware
Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States, 19803
United States, District of Columbia
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
United States, Florida
Nemours Children's Clinic
Jacksonville, Florida, United States, 32207
University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami, Florida, United States, 33136
United States, Georgia
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
Atlanta, Georgia, United States, 30322
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
University of Illinois Cancer Center
Chicago, Illinois, United States, 60612-7243
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
United States, Texas
Cook Children's Medical Center - Fort Worth
Fort Worth, Texas, United States, 76104
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Baylor University Medical Center - Houston
Houston, Texas, United States, 77030-2399
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
Australia, New South Wales
Children's Hospital at Westmead
Westmead, New South Wales, Australia, 2145

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Rima Jubran, MD, MPH	Children's Hospital Los Angeles
Investigator:	Timothy G. Murray, MD	University of Miami Sylvester Comprehensive Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Gregory H. Reaman, Children's Oncology Group - Group Chair Office
ClinicalTrials.gov Identifier:	NCT00072384 History of Changes
Other Study ID Numbers:	CDR0000339627, COG-ARET0231
Study First Received:	November 4, 2003
Last Updated:	February 1, 2011
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

intraocular retinoblastoma

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
Vincristine

Etoposide phosphate
Carboplatin
Lenograstim
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 12, 2012