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

Intraocular Retinoblastoma Clinical Trial

Official title:

A Study of Unilateral Retinoblastoma With and Without Histopathologic High-Risk Features and the Role of Adjuvant Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00335738
• Other study ID #: ARET0332
• Secondary ID: NCI-2009-00423CD
• Status: Completed
• Phase: Phase 3
• Start date: December 2005
• Est. completion date: September 30, 2020

Study information

• Verified date: March 2018
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 331
• Est. completion date: September 30, 2020
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 6 Years

Eligibility

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

Related Conditions & MeSH terms

• Intraocular Retinoblastoma
• Retinoblastoma

Intervention

Drug:
• liposomal vincristine sulfate
Given IV
• carboplatin
Given IV
• etoposide
Given IV

Locations

Country	Name	City	State
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Canada	Hospital Sainte-Justine	Montreal	Quebec
Canada	CancerCare Manitoba	Winnipeg	Manitoba
India	L V Prasad Eye Institute	Hyderabad
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Starship Children's Hospital	Grafton	Auckland
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Children's Oncology Group	Arcadia	California
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Johns Hopkins University	Baltimore	Maryland
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Brooklyn Hospital Center	Brooklyn	New York
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Childrens Memorial Hospital	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Rainbow Babies and Childrens Hospital	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	The Children's Medical Center of Dayton	Dayton	Ohio
United States	Wayne State University	Detroit	Michigan
United States	Southern California Permanente Medical Group	Downey	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Baylor College of Medicine	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	The Childrens Mercy Hospital	Kansas City	Missouri
United States	University of Kentucky	Lexington	Kentucky
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Kosair Children's Hospital	Louisville	Kentucky
United States	Covenant Children's Hospital	Lubbock	Texas
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	University of Minnesota Medical Center-Fairview	Minneapolis	Minnesota
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Childrens Hospital-King's Daughters	Norfolk	Virginia
United States	Children's Hospital and Medical Center of Omaha	Omaha	Nebraska
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Primary Children's Medical Center	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Rady Children's Hospital - San Diego	San Diego	California
United States	University of California San Francisco Medical Center-Parnassus	San Francisco	California
United States	Maine Children's Cancer Program	Scarborough	Maine
United States	Scott and White Memorial Hospital	Temple	Texas
United States	University of Arizona Health Sciences Center	Tucson	Arizona
United States	Children's National Medical Center	Washington	District of Columbia
United States	Lombardi Comprehensive Cancer Center at Georgetown University	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada,  India,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free Survival (EFS)	EFS distributions will be estimated by the Kaplan-Meier method for patients with high risk features according to central review and treated with adjuvant chemotherapy and separately for subjects with central review recommendation of enucleation alone.	At 2 years
Primary	Overall Survival (OS)	OS distributions will be estimated by the Kaplan-Meier method for patients with high risk features according to central review and treated with adjuvant chemotherapy and separately for subjects with central review recommendation of enucleation alone.	At 2 Years
Secondary	Toxicity As Assessed By the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0	Number of patients assigned chemotherapy who experienced grade 3 or higher CTC AE toxicity.	During planned six cycles of chemotherapy
Secondary	Pathological Features Present At Diagnosis - Posterior Uveal Invasion (PVI)	Proportion of patients who had posterior uveal invasion at enrollment.	At enrollment
Secondary	Pathological Features Present At Diagnosis - Tumor Involving the Optic Nerve Posterior to the Lamina Cribrosa (LC) as an Independent Finding	Proportion of patients with tumor involving the optic nerve posterior to the lamina cribrosa as an independent.	At enrollment
Secondary	Pathological Features Present at Diagnosis - Scleral Invasion (SI)	Proportion of patients that had scleral invasion at enrollment.	At enrollment
Secondary	Pathological Features Present At Diagnosis - Anterior Chamber Seeding (ACS)	Proportion of patients who had anterior chamber seeding at enrollment.	At enrollment
Secondary	Pathological Features Present At Diagnosis - Iris Infiltration (II)	Proportion of patients who had iris infiltration at enrollment.	At enrollment
Secondary	Pathological Features Present At Diagnosis - Ciliary Body Infiltration (CBI)	Proportion of patients who had ciliary body infiltration at enrollment.	At Enrollment

External Links

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