Vincristine, Carboplatin, and Etoposide or Observation Only in Treating Patients Who Have Undergone Surgery for Newly Diagnosed Retinoblastoma

NCT ID: NCT00335738

Last Updated: 2021-02-18

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

331 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-12-31

Study Completion Date

2020-09-30

Brief Summary

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This phase III trial is studying vincristine, carboplatin, and etoposide to see how well they work compared to observation only in treating patients who have undergone surgery for newly diagnosed retinoblastoma. Drugs used in chemotherapy, such as vincristine, carboplatin, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) after surgery may kill any tumor cells that remain after surgery. Sometimes, after surgery, no additional treatment is needed for the tumor until it progresses. In this case, observation may be sufficient.

Detailed Description

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OBJECTIVES:

I. Prospectively determine the prevalence of high-risk histopathologic features, such as choroidal involvement, optic nerve invasion, and scleral and anterior segment involvement, in patients with newly diagnosed unilateral retinoblastoma who have undergone enucleation.

II. Demonstrate that patients without certain high-risk features can be successfully treated with enucleation alone by estimating the event-free survival (EFS) (where an event is defined as the occurrence of extraocular or metastatic disease) and overall survival (OS).

III. Estimate the EFS and OS of patients with specific high-risk features who are uniformly treated with adjuvant chemotherapy comprising vincristine, carboplatin, and etoposide.

IV. Estimate the incidence of toxicities associated with the proposed adjuvant chemotherapy regimen.

OUTLINE: This is a prospective, nonrandomized, multicenter study. Patients are assigned to 1 of 2 groups according to presence of high-risk histopathologic features.

GROUP 1 (high-risk features): Patients receive vincristine IV and carboplatin IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

GROUP 2 (no high-risk features): Patients undergo observation periodically for at least 5 years.

GROUP 3 (no consensus regarding high risk features can be reached): Patients undergo Group 1 chemotherapy or observation according to institutional high-risk feature assessment.

After completion of study treatment, patients in group 1 are followed periodically for at least 5 years.

Conditions

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Intraocular Retinoblastoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Group 1 (identified by central review as high risk)

Includes patients who may or may not require chemotherapy. Patients who require chemotherapy receive vincristine IV and carboplatin IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity and patients who complete chemotherapy are followed after completion of therapy periodically for at least 5 years. Patients who do not require chemotherapy undergo observation periodically for at least 5 years.

Group Type EXPERIMENTAL

liposomal vincristine sulfate

Intervention Type DRUG

Given IV

carboplatin

Intervention Type DRUG

Given IV

etoposide

Intervention Type DRUG

Given IV

Group 2 (identified by central review as not high risk)

Patients undergo observation periodically for at least 5 years.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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liposomal vincristine sulfate

Given IV

Intervention Type DRUG

carboplatin

Given IV

Intervention Type DRUG

etoposide

Given IV

Intervention Type DRUG

Other Intervention Names

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liposomal vincristine Marqibo vincristine liposomal vincristine sulfate liposome injection Carboplat CBDCA JM-8 Paraplat Paraplatin EPEG VP-16 VP-16-213

Eligibility Criteria

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Inclusion Criteria

* Newly diagnosed unilateral retinoblastoma
* Underwent enucleation as primary therapy within the past 5 weeks

* Must enroll and submit pathology slides within 21 days of enucleation
* Adjuvant chemotherapy must begin within 35 days after enucleation
* Disease with or without high-risk histopathologic features

* High-risk features are defined as any of the following:

* Posterior uveal invasion (includes choroidal invasion)
* Any degree of concomitant choroid and/or optic nerve involvement
* Tumor involving the optic nerve posterior to the lamina cribrosa as an independent finding
* Scleral invasion
* Anterior chamber seeding
* Ciliary body infiltration
* Iris infiltration
* No evidence of extraocular retinoblastoma clinically, by CT scan, or by MRI of the brain and orbits with and without gadolinium
* No tumor at the cut end of the optic nerve on any eye enucleated as evidenced by histologic examination prior to study entry
* No systemic metastases as evidenced by bone marrow scan, bone scan, or any other additional test at study entry
* Lansky performance status 50-100%
* Hemoglobin \> 8 g/dL
* Absolute neutrophil count ≥ 1,000/mm³
* Platelet count ≥ 100,000/mm³
* 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
* Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
* AST or ALT \< 2.5 times ULN for age
* No prior therapy other than enucleation
* No prior chemotherapy
Maximum Eligible Age

6 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Murali Chintagumpala, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

University of Arizona Health Sciences Center

Tucson, Arizona, United States

Site Status

Children's Oncology Group

Arcadia, California, United States

Site Status

Southern California Permanente Medical Group

Downey, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Rady Children's Hospital - San Diego

San Diego, California, United States

Site Status

University of California San Francisco Medical Center-Parnassus

San Francisco, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

Lombardi Comprehensive Cancer Center at Georgetown University

Washington D.C., District of Columbia, United States

Site Status

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Site Status

University of Illinois

Chicago, Illinois, United States

Site Status

Childrens Memorial Hospital

Chicago, Illinois, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

Kosair Children's Hospital

Louisville, Kentucky, United States

Site Status

Maine Children's Cancer Program

Scarborough, Maine, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Wayne State University

Detroit, Michigan, United States

Site Status

University of Minnesota Medical Center-Fairview

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

The Childrens Mercy Hospital

Kansas City, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, United States

Site Status

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Site Status

Brooklyn Hospital Center

Brooklyn, New York, United States

Site Status

Carolinas Medical Center

Charlotte, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Rainbow Babies and Childrens Hospital

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

The Children's Medical Center of Dayton

Dayton, Ohio, United States

Site Status

Lehigh Valley Hospital - Muhlenberg

Bethlehem, Pennsylvania, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Cook Children's Medical Center

Fort Worth, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

M D Anderson Cancer Center

Houston, Texas, United States

Site Status

Covenant Children's Hospital

Lubbock, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Scott and White Memorial Hospital

Temple, Texas, United States

Site Status

Primary Children's Medical Center

Salt Lake City, Utah, United States

Site Status

Childrens Hospital-King's Daughters

Norfolk, Virginia, United States

Site Status

Marshfield Clinic

Marshfield, Wisconsin, United States

Site Status

Midwest Children's Cancer Center

Milwaukee, Wisconsin, United States

Site Status

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Site Status

Royal Children's Hospital

Parkville, Victoria, Australia

Site Status

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Site Status

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Site Status

Hospital Sainte-Justine

Montreal, Quebec, Canada

Site Status

L V Prasad Eye Institute

Hyderabad, , India

Site Status

Starship Children's Hospital

Grafton, Auckland, New Zealand

Site Status

Christchurch Hospital

Christchurch, , New Zealand

Site Status

Countries

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United States Australia Canada India New Zealand

Related Links

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https://nctn-data-archive.nci.nih.gov/

Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive

Other Identifiers

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NCI-2009-00423

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000483043

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA098543

Identifier Type: NIH

Identifier Source: secondary_id

View Link

COG-ARET0332

Identifier Type: OTHER

Identifier Source: secondary_id

ARET0332

Identifier Type: -

Identifier Source: org_study_id

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