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

Children's Oncology Group

Status and phase: Completed; Phase 3

Conditions: Intraocular Retinoblastoma

Treatments: Drug: carboplatin; Drug: liposomal vincristine sulfate; Drug: etoposide

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00335738

COG-ARET0332 (Other Identifier)

NCI-2009-00423 (Registry Identifier)

U10CA098543 (U.S. NIH Grant/Contract)

ARET0332

CDR0000483043 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 331 patients

Sex: All

Ages: Under 6 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

331 participants in 2 patient groups

Group 1 (identified by central review as high risk)

Experimental group

Description:

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.

Treatment:

Drug: etoposide

Drug: liposomal vincristine sulfate

Drug: carboplatin

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

No Intervention group

Description:

Patients undergo observation periodically for at least 5 years.