Neoadjuvant Carboplatin and Vincristine and Standard Local Ophthalmic Therapy in Treating Patients With Intraocular Retinoblastoma - Full Text View

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:

Genetics Home Reference related topics: retinoblastoma

Drug Information available for: Vincristine sulfate Ruthenium Iodine Sulfate ion Carboplatin

Genetic and Rare Diseases Information Center resources: Retinoblastoma Neuroepithelioma

U.S. FDA Resources

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 ]
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:

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

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 (Child)
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
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


Principal Investigator:	Debra Friedman, MD	Children's Oncology Group

More Information


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:	March 14, 2016
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 Carboplatin	Vincristine Iodine 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 Growth Substances Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 23, 2016