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

Trial of Systemic Neoadjuvant Chemotherapy for Group B Intraocular Retinoblastoma

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.

Study Overview

• Status: Completed
• Conditions: Intraocular Retinoblastoma
• Intervention / Treatment: Drug: Carboplatin; Drug: Vincristine Sulfate; Procedure: Cryosurgery; Procedure: Infrared Laser Therapy; Radiation: Iodine I-125; Radiation: Radiation Therapy; Radiation: Ruthenium Ru-106

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: Interventional
• Enrollment (Actual): 28
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Lurie Children's Hospital-Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Oncology Group
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (chemotherapy, surgery); 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.

Drug: Carboplatin; Given IV; Other Names: Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carboplatinum; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo; Drug: Vincristine Sulfate; Given IV; Other Names: Oncovin; Kyocristine; Leurocristine Sulfate; Leurocristine, sulfate; Vincasar; Vincosid; Vincrex; Vincristine, sulfate; Procedure: Cryosurgery; Other Names: Cryoablation; cryosurgical ablation; Ablation, Cryo; Procedure: Infrared Laser Therapy; Radiation: Iodine I-125; Undergo radioactive therapy; Other Names: 125-Iodine; I-125; Iodine 125; Iodine I 125; Radiation: Radiation Therapy; Undergo radioactive therapy; Other Names: Cancer Radiotherapy; ENERGY_TYPE; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; Radiation: Ruthenium Ru-106; Undergo radioactive therapy; Other Names: Ru-106; Ruthenium Ru 106

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free Survival	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.	At 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate (RR) at Patient Level After the First Course of Therapy	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	1 month after enrollment
Response Rate (RR) at Eye Levels After the First Course of Therapy	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	1 month after enrollment
Event-free Survival Rate (EFSR) Defined as the Need for Non-protocol Chemotherapy, Enucleation, or EBRT at the Patient Level	EFSR will be estimated for patients who respond to vincristine and carboplatin after an initial 1 cycle of chemoreduction	2 years after enrollment
Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0	Participants with Grade 3 and higher reported on protocol therapy	6 months after enrollment

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Debra L Friedman, Children's Oncology Group

Study record dates

Study Major Dates

• Study Start (Actual): December 26, 2005
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): March 31, 2017

Study Registration Dates

• First Submitted: March 8, 2004
• First Submitted That Met QC Criteria: March 9, 2004
• First Posted (Estimate): March 10, 2004

Study Record Updates

• Last Update Posted (Actual): March 13, 2023
• Last Update Submitted That Met QC Criteria: February 14, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Eye Diseases; Retinal Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Eye Diseases, Hereditary; Eye Neoplasms; Retinal Neoplasms; Retinoblastoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents, Local; Anti-Infective Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Trace Elements; Micronutrients; Carboplatin; Iodine; Cadexomer iodine; Vincristine
• Other Study ID Numbers: ARET0331 (Other Identifier: CTEP); U10CA098543 (U.S. NIH Grant/Contract); NCI-2009-00422 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CDR0000355721 (Clinical Trials.gov); COG-ARET0331 (Children's Oncology Group)