Clinical trial NCT00079417: Neoadjuvant Carboplatin and Vincristine and Standard Local Ophthalmic Therapy in Treating Patients With Intraocular Retinoblastoma
Official title: Trial of Systemic Neoadjuvant Chemotherapy for Group B Intraocular Retinoblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Intraocular Retinoblastoma
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-03-10
Enrollment: 28
Sex: ALL
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Event-free Survival
timeFrame: At 2 years
Secondary outcomes:
measure: Response Rate (RR) at Patient Level After the First Course of Therapy
timeFrame: 1 month after enrollment
measure: Response Rate (RR) at Eye Levels After the First Course of Therapy
timeFrame: 1 month after enrollment
measure: Event-free Survival Rate (EFSR) Defined as the Need for Non-protocol Chemotherapy, Enucleation, or EBRT at the Patient Level
timeFrame: 2 years after enrollment
measure: Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0
timeFrame: 6 months after enrollment
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Chicago
country: United States
facility: Lurie Children's Hospital-Chicago
state: Illinois
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Oncology Group
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Children's Oncology Group
name: Debra L Friedman
role: PRINCIPAL_INVESTIGATOR
References: