Vincristine, Carboplatin, and Etoposide or Observation Only in Treating Patients Who Have Undergone Surgery for Newly Diagnosed Retinoblastoma
- Conditions
- Intraocular Retinoblastoma
- Interventions
- Registration Number
- NCT00335738
- Lead Sponsor
- Children's Oncology Group
- Brief 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.
- Detailed 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 & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 331
-
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
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 1 (identified by central review as high risk) liposomal vincristine sulfate 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 1 (identified by central review as high risk) carboplatin 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 1 (identified by central review as high risk) etoposide 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.
- Primary Outcome Measures
Name Time Method Event-free Survival (EFS) At 2 years 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.
Overall Survival (OS) At 2 Years 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.
- Secondary Outcome Measures
Name Time Method Toxicity As Assessed By the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 During planned six cycles of chemotherapy Number of patients assigned chemotherapy who experienced grade 3 or higher CTC AE toxicity.
Pathological Features Present At Diagnosis - Posterior Uveal Invasion (PVI) At enrollment Proportion of patients who had posterior uveal invasion at enrollment.
Pathological Features Present At Diagnosis - Tumor Involving the Optic Nerve Posterior to the Lamina Cribrosa (LC) as an Independent Finding At enrollment Proportion of patients with tumor involving the optic nerve posterior to the lamina cribrosa as an independent.
Pathological Features Present at Diagnosis - Scleral Invasion (SI) At enrollment Proportion of patients that had scleral invasion at enrollment.
Pathological Features Present At Diagnosis - Anterior Chamber Seeding (ACS) At enrollment Proportion of patients who had anterior chamber seeding at enrollment.
Pathological Features Present At Diagnosis - Iris Infiltration (II) At enrollment Proportion of patients who had iris infiltration at enrollment.
Pathological Features Present At Diagnosis - Ciliary Body Infiltration (CBI) At Enrollment Proportion of patients who had ciliary body infiltration at enrollment.
Trial Locations
- Locations (56)
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Rainbow Babies and Childrens Hospital
🇺🇸Cleveland, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Marshfield Clinic
🇺🇸Marshfield, Wisconsin, United States
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
Southern California Permanente Medical Group
🇺🇸Downey, California, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
L V Prasad Eye Institute
🇮🇳Hyderabad, India
The Childrens Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Lombardi Comprehensive Cancer Center at Georgetown University
🇺🇸Washington, District of Columbia, United States
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Brooklyn Hospital Center
🇺🇸Brooklyn, New York, United States
Scott and White Memorial Hospital
🇺🇸Temple, Texas, United States
Christchurch Hospital
🇳🇿Christchurch, New Zealand
Rady Children's Hospital - San Diego
🇺🇸San Diego, California, United States
University of California San Francisco Medical Center-Parnassus
🇺🇸San Francisco, California, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Wayne State University
🇺🇸Detroit, Michigan, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
University of Minnesota Medical Center-Fairview
🇺🇸Minneapolis, Minnesota, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Primary Children's Medical Center
🇺🇸Salt Lake City, Utah, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
M D Anderson Cancer Center
🇺🇸Houston, Texas, United States
Hospital Sainte-Justine
🇨🇦Montreal, Quebec, Canada
Starship Children's Hospital
🇳🇿Grafton, Auckland, New Zealand
Childrens Memorial Hospital
🇺🇸Chicago, Illinois, United States
University of Arizona Health Sciences Center
🇺🇸Tucson, Arizona, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Children's Oncology Group
🇺🇸Arcadia, California, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Kosair Children's Hospital
🇺🇸Louisville, Kentucky, United States
Maine Children's Cancer Program
🇺🇸Scarborough, Maine, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Children's Hospital and Medical Center of Omaha
🇺🇸Omaha, Nebraska, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Childrens Hospital-King's Daughters
🇺🇸Norfolk, Virginia, United States
The Children's Medical Center of Dayton
🇺🇸Dayton, Ohio, United States
Lehigh Valley Hospital - Muhlenberg
🇺🇸Bethlehem, Pennsylvania, United States
Covenant Children's Hospital
🇺🇸Lubbock, Texas, United States
Midwest Children's Cancer Center
🇺🇸Milwaukee, Wisconsin, United States
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Royal Children's Hospital
🇦🇺Parkville, Victoria, Australia
Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States