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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00079417
First received: March 8, 2004
Last updated: December 23, 2013
Last verified: December 2013
  Purpose

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 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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Trial of Systemic Neoadjuvant Chemotherapy for Group B Intraocular Retinoblastoma

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Event-free Survival [ Time Frame: At 2 years ] [ Designated as safety issue: No ]
    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:
  • Use of Nonprotocol Chemotherapy [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Use of nonprotocol chemotherapy at the patient level and enucleation and EBRT will be descriptively summarized at the patient and eye levels.

  • Response Rate (RR) at Patient and Eye Levels After the First Course [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    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.

  • Event-free Survival Rate (EFSR) Defined as the Need for Non-protocol Chemotherapy, Enucleation, or EBRT at the Patient Level [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    EFSR will be estimated for patients who respond to vincristine and carboplatin after an initial 1 cycle of chemoreduction

  • Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 [ Time Frame: From the beginning of treatment, assessed up to 10 years ] [ Designated as safety issue: Yes ]

Enrollment: 28
Study Start Date: December 2005
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   up to 5 Years
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00079417

Locations
United States, California
Children's Oncology Group
Arcadia, California, United States, 91006-3776
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
Investigators
Principal Investigator: Debra Friedman Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00079417     History of Changes
Other Study ID Numbers: ARET0331, NCI-2009-00422, CDR0000355721, COG-ARET0331, U10CA098543
Study First Received: March 8, 2004
Results First Received: December 23, 2013
Last Updated: December 23, 2013
Health Authority: United States: Institutional Review Board

Additional relevant 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
Retinal Diseases
Iodine
Cadexomer iodine
Vincristine
Carboplatin
Anti-Infective Agents, Local
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on August 26, 2014