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Systemic Chemotherapy and Subtenon Carboplatin, and Local Ophthalmic Therapy in Children With Intraocular Retinoblastoma

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ClinicalTrials.gov Identifier: NCT00072384
Recruitment Status : Completed
First Posted : November 6, 2003
Results First Posted : September 19, 2018
Last Update Posted : July 30, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Tracking Information
First Submitted Date  ICMJE November 4, 2003
First Posted Date  ICMJE November 6, 2003
Results First Submitted Date  ICMJE November 25, 2015
Results First Posted Date  ICMJE September 19, 2018
Last Update Posted Date July 30, 2021
Actual Study Start Date  ICMJE April 16, 2007
Actual Primary Completion Date February 1, 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 21, 2018)
  • Group D Eyes - Treatment Failure Within One Year [ Time Frame: One year ]
    Each Group D eye will be classified as experiencing failure within one year after start of treatment: yes or no. The method of Rosner et al. (Biometrics v. 38, 105-114, 1982) will be used to model possible dependence between eyes from the same patient. The point estimate of the probability of treatment failure is reported as the "Mean" measure type.
  • Group C Eyes - Treatment Failure Within One Year [ Time Frame: One year ]
    Each Group C eye will be classified as experiencing failure within one year after start of treatment: yes or no. The method of Rosner et al. (Biometrics v. 38, 105-114, 1982) will be used to model possible dependence between eyes from the same patient. The point estimate of the probability of treatment failure is reported as the "Mean" measure type.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 21, 2018)
  • Event-free Survival (EFS) [ Time Frame: One year after study enrollment ]
    Proportion of patients event free at 1 year following enrollment. Event free survival time is computed as the time to study entry until disease relapse/progression, secondary malignancy, or death.
  • Toxicity Associated With Chemotherapy [ Time Frame: From date of enrollment until termination of protocol therapy assessed up to 72 weeks ]
    The number of patients that experience CTC Version 4 grade 3 or higher toxicities of any kind.
  • Patterns of Failure for Group C and Group D in Terms of Vitreous vs Patterns of Failure for Group C and Group D in Terms of Vitreous vs Retinal vs Both as Sites of Recurrence [ Time Frame: From the date of enrollment assessed up to 36 months ]
    Sites of disease recurrence for Group C and Group D eyes where treatment failure was detected
  • Patterns of Treatment Failure vs. no Treatment Failure for Group C Eyes and Group D Eyes According to Initial Sites of Involvement [ Time Frame: From the date of enrollment assessed up to 12 months ]
    The association between the probability of experiencing treatment failure vs. no failure in a C eye and the presence of subretinal seeding (SRS), subretinal fluid (SRF), or vitreal seeding (VS) at the on study ophthalmological examination under anesthesia. The association between the probability of experiencing treatment failure vs. no failure in a D eye and the presence of subretinal seeding (SRS), subretinal fluid (SRF), or vitreal seeding (VS) at the on study ophthalmological examination under anesthesia.
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 Systemic Chemotherapy and Subtenon Carboplatin, and Local Ophthalmic Therapy in Children With Intraocular Retinoblastoma
Official Title  ICMJE A Single Arm Trial of Systemic And Subtenon Chemotherapy For Groups C And D Intraocular Retinoblastoma
Brief Summary Phase III trial to determine the effectiveness of combining systemic chemotherapy and subtenon carboplatin with ophthalmic therapy in treating children who have intraocular retinoblastoma. Drugs used in chemotherapy, such as vincristine, carboplatin, and etoposide, work in different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether systemic chemotherapy and subtenon (under the conjunctiva of the eye) carboplatin combined with ophthalmic therapy is effective in treating intraocular (within the eyeball) retinoblastoma.
Detailed Description

PRIMARY OBJECTIVES:

I. Determine the event-free survival at 12 months of pediatric patients' eyes with group D intraocular retinoblastoma treated with systemic chemotherapy comprising vincristine, carboplatin, and etoposide, subtenon carboplatin, and local ophthalmic therapy. (Event defined for each eye individually as needed for nonprotocol therapy including nonprotocol chemotherapy, enucleation or any external-beam radiation)

SECONDARY OBJECTIVES:

I. Determine the event-free survival at 12 months of pediatric patients' eyes with group C retinoblastoma treated with systemic chemotherapy comprising carboplatin, etoposide, vincristine, subtenon carboplatin, and local ophthalmic therapy.

II. Determine the acute and long-term toxic effects of these regimens in these patients, including visual outcome and incidence of secondary malignancies.

III. Determine the patterns of failure in patients treated with these regimens, in terms of vitreous vs retinal vs both as sites of recurrence.

IV. Determine predictors of failure including findings at the on study examination under anesthesia and response status after six courses of chemotherapy.

V. Determine the percentage of group C and D eyes separately that can be preserved without enucleation after failing protocol therapy.

OUTLINE: This is a multicenter study.

Patients receive vincristine IV over 1 minute on day 1 and carboplatin IV over 1 hour and etoposide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 3 and continuing until blood counts recover. Patients receive subtenon carboplatin to each group C or D eye on day 0 or 1 prior of courses 2-4 only. Treatment repeats every 28 days for 6 courses in the absence of occurrence of extraocular retinoblastoma or a second malignancy. Beginning with course 3 of systemic chemotherapy, patients undergo local ophthalmic therapy comprising local laser and/or cryotherapy on day 1.

Patients are followed with ophthalmology exams every 4-12 weeks until 3 years of age, every 6 months until 5 years of age, and then annually for up to 10 years.

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
  • Drug: liposomal vincristine sulfate
    Given IV
    Other Names:
    • liposomal vincristine
    • Marqibo
    • vincristine liposomal
    • vincristine sulfate liposome injection
  • Procedure: cryosurgery
    Application of extreme cold to destroy abnormal or diseased tissue.
    Other Names:
    • cryoablation
    • cryosurgical ablation
  • Procedure: laser surgery
    Surgery using a laser (instead of a scalpel) to cut tissue
    Other Names:
    • conventional laser therapy
    • laser therapy, conventional
    • surgery, laser
  • Drug: carboplatin
    Given IV
    Other Names:
    • Carboplat
    • CBDCA
    • JM-8
    • Paraplat
    • Paraplatin
  • Drug: etoposide
    Given IV
    Other Names:
    • EPEG
    • VP-16
    • VP-16-213
  • Biological: filgrastim
    Given subcutaneously
    Other Names:
    • G-CSF
    • Neupogen
Study Arms  ICMJE Experimental: Treatment (chemotherapy, surgery)
Patients receive liposomal vincristine sulfate IV over 1 minute on day 1 and carboplatin IV over 1 hour and etoposide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 3 and continuing until blood counts recover. Patients receive subtenon carboplatin to each group C or D eye on day 0 or 1prior of courses 2-4 only. Treatment repeats every 28 days for 6 courses in the absence of occurrence of extraocular retinoblastoma or a second malignancy. Beginning with course 3 of systemic chemotherapy, patients undergo local ophthalmic therapy comprising local laser surgery and/or cryosurgery on day 1.
Interventions:
  • Drug: liposomal vincristine sulfate
  • Procedure: cryosurgery
  • Procedure: laser surgery
  • Drug: carboplatin
  • Drug: etoposide
  • Biological: filgrastim
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)
30
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE June 30, 2021
Actual Primary Completion Date February 1, 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of bilateral retinoblastoma with at least 1 eye group C or D intraocular retinoblastoma by ophthalmologic examination, defined by the International Classification System for Intraocular Retinoblastoma as the following:

    • Group C: Discrete localized disease with minimal subretinal and/or vitreous seeding

      • Subretinal fluid, without prior or concurrent seeding, involving ≤ one quarter of the retina
      • Local fine vitreous seeding may be present close to discrete tumor
      • Local subretinal seeding < 3 mm from tumor
    • Group D: Diffuse disease with significant vitreous and/or subretinal seeding

      • Tumor(s) may be massive or diffuse
      • Subretinal fluid, without prior or concurrent seeding, involving up to total retinal detachment
      • Diffuse or massive vitreous disease may include "greasy" seeds or avascular tumor masses
      • Diffuse subretinal seeding may include subretinal plaques or tumor nodules
  • Prior enucleation of 1 eye allowed provided the remaining eye is group C or D
  • No tumor present on histologic examination at the cut end of the optic nerve on any eye enucleated prior to study entry

    • Evidence of choroidal and/or optic nerve invasion past the lumina cribrosa is allowed
  • No extraocular retinoblastoma clinically or by MRI of brain and orbits with and without gadolinium or CT scan with and without contrast of brain and orbits
  • No evidence of systemic metastases by bone marrow, lumbar puncture, bone scan, and/or any other additional test
  • Performance status - Karnofsky 50-100% (over 16 years of age)
  • Performance status - Lansky 50-100% (16 and under)
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
  • AST and ALT < 2.5 times ULN for age
  • Creatinine adjusted according to age as follows:

    • No greater than 0.4 mg/dL (≤ 5 months)
    • No greater than 0.5 mg/dL (6 months -11 months)
    • No greater than 0.6 mg/dL (1 year-23 months)
    • No greater than 0.8 mg/dL (2 years-5 years)
    • No greater than 1.0 mg/dL (6 years-9 years)
    • No greater than 1.2 mg/dL (10 years-12 years)
    • No greater than 1.4 mg/dL (13 years and over [female])
    • No greater than 1.5 mg/dL (13 years to 15 years [male])
    • No greater than 1.7 mg/dL (16 years and over [male])
  • Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min/1.73m^2
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • Negative pregnancy test in postmenarchal females
  • No prior chemotherapy
  • No other concurrent chemotherapy
  • No prior radiotherapy
  • No other concurrent radiotherapy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 17 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 Australia
 
Administrative Information
NCT Number  ICMJE NCT00072384
Other Study ID Numbers  ICMJE ARET0231
NCI-2009-00420 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000339627 ( Other Identifier: Clinical Trials.gov )
COG-ARET0231 ( 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: Rima Jubran Children's Oncology Group
PRS Account Children's Oncology Group
Verification Date July 2021

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