Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Active	Under 18	NCI	COG-ARET0231 ARET0231, NCT00072384

Objectives

Primary

1. 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

1. 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.
2. Determine the acute and long-term toxic effects of these regimens in these patients, including visual outcome and incidence of secondary malignancies.
3. Determine the patterns of failure in patients treated with these regimens, in terms of vitreous vs retinal vs both as sites of recurrence.
4. Determine predictors of failure including findings at the on study examination under anesthesia and response status after six courses of chemotherapy.
5. Determine the percentage of group C and D eyes separately that can be preserved without enucleation after failing protocol therapy.

Entry 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

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

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/1.73m²

Other

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

Expected Enrollment

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

Outcomes

Event-free survival at 12 months of pediatric patients' eyes with intraocular group C and/or D retinoblastoma

Acute and long-term toxic effects
Patterns of failure
Predictors of failure
Percentage of preservation without enucleation after failed treatment

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.

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Rima Jubran, MD, Protocol chair		Ph: 323-669-5639 Email: rjubran@chla.usc.edu
Timothy Murray, MD, Protocol co-chair		Ph: 305-326-6000

U.S.A.
California
	Los Angeles
	Childrens Hospital Los Angeles
		Leo Mascarenhas	Ph:  323-361-2529
Florida
	Miami
	University of Miami Sylvester Comprehensive Cancer Center - Miami
		University of Miami Sylvester Comprehensive Cancer Center Clinical Trial Matching Service	Ph:  866-574-5124
			Email: Sylvester@emergingmed.com
Georgia
	Atlanta
	Winship Cancer Institute of Emory University
		Howard Katzenstein	Ph:  404-785-0853
Illinois
	Chicago
	Children's Memorial Hospital - Chicago
		Stewart Goldman	Ph:  773-880-3270
	University of Illinois Cancer Center
		Clinical Trial Office - University of Illinois Cancer Center	Ph:  312-355-3046
North Carolina
	Durham
	Duke Comprehensive Cancer Center
		Clinical Trials Office - Duke Comprehensive Cancer Center	Ph:  888-275-3853
Ohio
	Cincinnati
	Cincinnati Children's Hospital Medical Center
		Clinical Trials Office - Cincinnati Children's Hospital Medical Center	Ph:  513-636-2799
Texas
	Houston
	Baylor University Medical Center - Houston
		Patrick Thompson	Ph:  832-824-4029
	M. D. Anderson Cancer Center at University of Texas
		Clinical Trials Office - M. D. Anderson Cancer Center at the University of Texas	Ph:  713-792-3245
Washington
	Seattle
	Children's Hospital and Regional Medical Center - Seattle
		Julie Park	Ph:  206-987-2106

Registry Information
Official Title		A Single Arm Trial of Systemic And Subtenon Chemotherapy For Groups C And D Intraocular Retinoblastoma
Trial Start Date		2007-04-16
Trial Completion Date		2010-02-14 (estimated)
Registered in ClinicalTrials.gov		NCT00072384 1
Date Submitted to PDQ		2003-09-30
Information Last Verified		2009-11-25
NCI Grant/Contract Number		CA98543

Table of Links

1	http://clinicaltrials.gov/ct/show/NCT00072384