Neoadjuvant Carboplatin and Vincristine and Standard Local Ophthalmic Therapy in Treating Patients With Intraocular Retinoblastoma

Children's Oncology Group

Status and phase

Completed

Phase 3

Conditions

Intraocular Retinoblastoma

Treatments

Procedure: Cryosurgery

Drug: Vincristine Sulfate

Procedure: Infrared Laser Therapy

Radiation: Iodine I-125

Radiation: Ruthenium Ru-106

Radiation: Radiation Therapy

Drug: Carboplatin

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT00079417

COG-ARET0331 (Other Identifier)

NCI-2009-00422 (Registry Identifier)

U10CA098543 (U.S. NIH Grant/Contract)

CDR0000355721 (Other Identifier)

ARET0331

Details and patient eligibility

About

This phase III trial is studying how well giving carboplatin and vincristine together with standard local ophthalmic therapy works in treating children with intraocular retinoblastoma. Drugs used in chemotherapy, such as carboplatin and vincristine, work in different ways to stop tumor from dividing so they stop growing or die. It is not yet known whether neoadjuvant chemotherapy combined with standard local ophthalmic therapy is effective in treating intraocular retinoblastoma.

Full description

PRIMARY OBJECTIVES:

I. Determine the 2-year event-free survival of patients with Group B intraocular retinoblastoma treated with neoadjuvant chemoreduction comprising carboplatin and vincristine and standardized local ophthalmic therapy.

SECONDARY OBJECTIVES:

I. Determine the response rate after one course of chemoreduction (before standardized local ophthalmic therapy) in these patients.

II. Correlate response rate with event-free survival in patients treated with this regimen.

III. Determine the incidence of toxic effects in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive chemoreduction comprising carboplatin IV over 60 minutes followed by vincristine IV over 1-2 minutes on day 1. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. After the first course of chemoreduction, patients undergo standardized local ophthalmic therapy comprising local laser therapy, cryotherapy, and/or radioactive plaque comprising iodine I 125 or ruthenium Ru 106.

Patients are followed every 3-4 weeks until there is no active tumor seen on a minimum of 3 ophthalmic exams under anesthesia, every 6-8 weeks until 3 years of age, every 4-6 months until 10 years of age, and then annually thereafter.

Enrollment

28 patients

Sex

All

Ages

Under 5 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

Newly diagnosed Group B intraocular retinoblastoma meeting 1 of the following criteria:
- Group B tumor(s) in 1 eye
- Group B tumor(s) in both eyes
- Group A tumor in 1 eye and Group B tumor(s) in the other eye
- Group E tumor in 1 eye that has been enucleated and Group B tumor(s) in the remaining eye at the time of enucleation of the Group E tumor
Defined by the International Classification System for Intraocular Retinoblastoma as follows:
- Group A: Small tumors (≤ 3 mm in greatest dimension) confined to the retina, away from foveola and disc meeting the following criteria:
  - More than 3 mm from fovea
  - More than 1.5 mm from optic disk
- Group B: Tumors more than 3 mm meeting the following criteria:
  - Confined to the retina in any location not in Group A
  - Tumor associated subretinal fluid < 3 mm from the tumor margin with no subretinal seeding
- Group E: Must have ≥ 1 of the following present:
  - Tumor touching the lens
  - Tumor anterior to anterior vitreous face involving ciliary body or anterior segment
  - Diffuse infiltrating retinoblastoma
  - Neovascular glaucoma
  - Opaque media from hemorrhage
  - Tumor necrosis with aseptic orbital cellulites
  - Phthisis bulbi
Confirmation of diagnosis by CT scan or MRI of the brain and orbits AND an ophthalmologic evaluation under anesthesia within the past 3 weeks
No choroidal and/or optic nerve invasion past the lamina cribosa
No evidence of extraocular retinoblastoma clinically or by head and orbital MRI and/or CT scan
No tumor present on histological exam at the cut end of the optic nerve for any Group E eye enucleated before study entry
Performance status - ECOG 0-2
Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
AST or ALT < 2.5 times ULN for age
Creatinine clearance (based on Schwartz formula) or radioisotope glomerular filtration rate ≥ 70mL/min/1.73 m^2
No prior chemotherapy
No other concurrent chemotherapy
No prior radiotherapy
No other concurrent radiotherapy, including intensity-modulated stereotactic, or proton beam radiotherapy
Prior enucleation of one eye allowed provided the remaining eye is Group B
No concurrent enucleation
No prior local ophthalmic therapy for retinoblastoma
No other prior therapy for retinoblastoma
No local therapy during chemotherapy course 1