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

Sponsor:	Children's Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00335738

Purpose

RATIONALE: 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.

PURPOSE: 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.

Condition	Intervention	Phase
Retinoblastoma	Drug: carboplatin Drug: etoposide Drug: vincristine sulfate Other: clinical observation	Phase III

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Primary Purpose: Treatment
Official Title:	A Study of Unilateral Retinoblastoma With and Without Histopathologic High-Risk Features and the Role of Adjuvant Chemotherapy

Resource links provided by NLM:

Genetics Home Reference related topics: retinoblastoma

MedlinePlus related topics: Cancer

Drug Information available for: Vincristine Etoposide Carboplatin Etoposide phosphate Vincristine sulfate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Event-free survival at 2 years [ Designated as safety issue: No ]
Overall survival at 2 years [ Designated as safety issue: No ]

Secondary Outcome Measures:

Toxicity [ Designated as safety issue: Yes ]

Estimated Enrollment:	600
Study Start Date:	December 2005
Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 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.	Drug: carboplatin Given IV Drug: etoposide Given IV Drug: vincristine sulfate Given IV
No Intervention: Group 2 (no high-risk features) Patients undergo observation periodically for at least 5 years.	Other: clinical observation Patients undergo observation periodically for at least 5 years.

Detailed Description:

OBJECTIVES:

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

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

PROJECTED ACCRUAL: A total of 600 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	up to 6 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

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]) OR
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

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior therapy other than enucleation
No prior chemotherapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00335738

Show 98 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Murali M. Chintagumpala, MD	Texas Children's Cancer Center
Investigator:	Joan O'Brien, MD	University of California, San Francisco

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Gregory H. Reaman, Children's Oncology Group - Group Chair Office
ClinicalTrials.gov Identifier:	NCT00335738 History of Changes
Other Study ID Numbers:	CDR0000483043, COG-ARET0332
Study First Received:	June 8, 2006
Last Updated:	December 14, 2011
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

intraocular retinoblastoma

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

Etoposide
Vincristine
Etoposide phosphate
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012