Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00079417
Recruitment Status : Completed
First Posted : March 10, 2004
Results First Posted : February 14, 2014
Last Update Posted : September 27, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Intraocular Retinoblastoma Procedure: cryosurgery Procedure: infrared laser therapy Radiation: iodine I 125 Radiation: ruthenium Ru 106 Drug: carboplatin Drug: vincristine sulfate Radiation: radiation therapy Phase 3

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.

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Trial of Systemic Neoadjuvant Chemotherapy for Group B Intraocular Retinoblastoma
Actual Study Start Date : December 2005
Actual Primary Completion Date : January 2010
Actual Study Completion Date : January 2010

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Vincristine Sulfate and Carboplatin and surgery
Patients receive chemoreduction comprising carboplatin IV (Pts < 36 months: 18.6 mg/kg Pts ≥ 36 months: 560 mg/m2) over 60 minutes followed by vincristine sulfate IV (Pts < 36 months: 0.05 mg/kg Pts ≥36 months: 1.5 mg/m2) 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 infrared laser therapy, cryosurgery, and/or radiation therapy (radioactive) plaque comprising iodine I 125 or ruthenium Ru 106.
 Procedure: cryosurgery
Application of extreme cold to destroy abnormal or diseased tissue.
Other Names:
  • cryoablation
  • cryosurgical ablation

Procedure: infrared laser therapy
Laser therapy or "photobiomodulation" is the use of specific wavelength of light (red and near-infrared) to create therapeutic effects

Radiation: iodine I 125
Undergo radioactive therapy
Other Names:
  • 125-Iodine
  • I-125

Radiation: ruthenium Ru 106
Undergo radioactive therapy
Other Names:
  • Ru-106
  • Ruthenium 106

Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin

Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS

Radiation: radiation therapy
Undergo radioactive therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Event-free Survival [ Time Frame: At 2 years ]
    Proportion of patients with event free survival at 2 years. An event is defined as the need for non-protocol therapy, defined as additional on-protocol chemotherapy, enucleation or external beam radiation, among patients with Group B intraocular tumors with a schedule of neoadjuvant 2-agent (Vincristine/Carboplatin) chemotherapy (chemo-reduction) and standardized local ophthalmic therapy.


Secondary Outcome Measures :
  1. Response Rate (RR) at Patient Level After the First Course of Therapy [ Time Frame: 1 month after enrollment ]
    RR will be estimated. The response after 1 course of chemotherapy will be used to better define response to this neoadjuvant systemic chemotherapy, prior to the use of local ophthalmic therapy. Response to subsequent courses will help define response to combined systemic chemotherapy and local ophthalmic therapy. Number of patients with Type I, II, III or IV response after first course of therapy

  2. Response Rate (RR) at Eye Levels After the First Course of Therapy [ Time Frame: 1 month after enrollment ]
    RR will be estimated. The response after 1 course of chemotherapy will be used to better define response to this neoadjuvant systemic chemotherapy, prior to the use of local ophthalmic therapy. Response to subsequent courses will help define response to combined systemic chemotherapy and local ophthalmic therapy. Number eyes with Type I, II, III or IV response after first course of therapy

  3. Event-free Survival Rate (EFSR) Defined as the Need for Non-protocol Chemotherapy, Enucleation, or EBRT at the Patient Level [ Time Frame: 2 years after enrollment ]
    EFSR will be estimated for patients who respond to vincristine and carboplatin after an initial 1 cycle of chemoreduction

  4. Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 [ Time Frame: 6 months after enrollment ]
    Participants with Grade 3 and higher reported on protocol therapy


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 5 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00079417


Locations
Layout table for location information
United States, California
Children's Oncology Group
Monrovia, California, United States, 91016
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Debra Friedman, MD Children's Oncology Group
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00079417    
Other Study ID Numbers: ARET0331
NCI-2009-00422 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000355721 ( Other Identifier: Clinical Trials.gov )
COG-ARET0331 ( Other Identifier: Children's Oncology Group )
U10CA098543 ( U.S. NIH Grant/Contract )
First Posted: March 10, 2004    Key Record Dates
Results First Posted: February 14, 2014
Last Update Posted: September 27, 2018
Last Verified: August 2018
Additional relevant MeSH terms:
Layout table for 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, Hereditary
Eye Diseases
Retinal Diseases
 Iodine
Carboplatin
Vincristine
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents, Local
Anti-Infective Agents
Trace Elements
Micronutrients
Physiological Effects of Drugs