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

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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

Tracking Information
First Submitted Date  ICMJE March 8, 2004
First Posted Date  ICMJE March 10, 2004
Results First Submitted Date  ICMJE December 23, 2013
Results First Posted Date  ICMJE February 14, 2014
Last Update Posted Date September 27, 2018
Actual Study Start Date  ICMJE December 2005
Actual Primary Completion Date January 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 31, 2015)
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.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 30, 2018)
  • 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
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Neoadjuvant Carboplatin and Vincristine and Standard Local Ophthalmic Therapy in Treating Patients With Intraocular Retinoblastoma
Official Title  ICMJE Trial of Systemic Neoadjuvant Chemotherapy for Group B Intraocular Retinoblastoma
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Intraocular Retinoblastoma
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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.
Interventions:
  • Procedure: cryosurgery
  • Procedure: infrared laser therapy
  • Radiation: iodine I 125
  • Radiation: ruthenium Ru 106
  • Drug: carboplatin
  • Drug: vincristine sulfate
  • Radiation: radiation therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 18, 2013)
28
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE January 2010
Actual Primary Completion Date January 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 5 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00079417
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Children's Oncology Group
Study Sponsor  ICMJE Children's Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Debra Friedman, MD Children's Oncology Group
PRS Account Children's Oncology Group
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP