Systemic Chemotherapy and Subtenon Carboplatin, and Local Ophthalmic Therapy in Children With Intraocular Retinoblastoma

NCT ID: NCT00072384

Last Updated: 2021-07-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-16
• Study Completion Date: 2021-06-30

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.

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.

Conditions

Intraocular Retinoblastoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

liposomal vincristine sulfate

Intervention Type: DRUG

Given IV

cryosurgery

Intervention Type: PROCEDURE

Application of extreme cold to destroy abnormal or diseased tissue.

laser surgery

Intervention Type: PROCEDURE

Surgery using a laser (instead of a scalpel) to cut tissue

carboplatin

Intervention Type: DRUG

Given IV

etoposide

Intervention Type: DRUG

Given IV

filgrastim

Intervention Type: BIOLOGICAL

Given subcutaneously

Interventions

liposomal vincristine sulfate

Given IV

Intervention Type: DRUG

cryosurgery

Application of extreme cold to destroy abnormal or diseased tissue.

Intervention Type: PROCEDURE

laser surgery

Surgery using a laser (instead of a scalpel) to cut tissue

Intervention Type: PROCEDURE

carboplatin

Given IV

Intervention Type: DRUG

etoposide

Given IV

Intervention Type: DRUG

filgrastim

Given subcutaneously

Intervention Type: BIOLOGICAL

Other Intervention Names

liposomal vincristine; Marqibo; vincristine liposomal; vincristine sulfate liposome injection; cryoablation; cryosurgical ablation; conventional laser therapy; laser therapy, conventional; surgery, laser; Carboplat; CBDCA; JM-8; Paraplat; Paraplatin; EPEG; VP-16; VP-16-213; G-CSF; Neupogen

Eligibility 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

• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Children's Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rima Jubran

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

Children's Oncology Group

Arcadia, California, United States

Southern California Permanente Medical Group

Downey, California, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

Yale University

New Haven, Connecticut, United States

Lombardi Comprehensive Cancer Center at Georgetown University

Washington D.C., District of Columbia, United States

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, United States

University of Illinois

Chicago, Illinois, United States

Duke University Medical Center

Durham, North Carolina, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Baylor College of Medicine

Houston, Texas, United States

M D Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Other Identifiers

NCI-2009-00420

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000339627

Identifier Type: OTHER

Identifier Source: secondary_id

COG-ARET0231

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA098543

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ARET0231

Identifier Type: -

Identifier Source: org_study_id