RATIONALE: Drugs used in chemotherapy, such as carboplatin, etoposide, and vincristine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sometimes when chemotherapy is given, it does not stop the growth of tumor cells. The tumor is said to be resistant to chemotherapy. Giving cyclosporine together with chemotherapy may reduce drug resistance and allow the tumor cells to be killed. Cryotherapy kills tumor cells by freezing them. Laser therapy uses light to kill tumor cells. Giving combination chemotherapy together with cyclosporine followed by cryotherapy and/or laser therapy may be an effective treatment for retinoblastoma.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with cyclosporine followed by cryotherapy and/or laser therapy works in treating patients with newly diagnosed retinoblastoma in both eyes.

Condition	Treatment or Intervention	Phase
intraocular retinoblastoma	Drug: carboplatin  Drug: cyclosporine  Drug: etoposide  Drug: filgrastim  Drug: vincristine  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cryosurgery  Procedure: cytokine therapy  Procedure: drug resistance inhibition  Procedure: high-dose chemotherapy  Procedure: laser surgery  Procedure: laser therapy  Procedure: neoadjuvant therapy  Procedure: phototherapy  Procedure: surgery	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Compare the efficacy of neoadjuvant high-dose carboplatin and etoposide, vincristine, and cyclosporine (CSA) followed by ophthalmic focal therapy comprising cryotherapy and/or laser therapy to historical world data of chemotherapy treatment without CSA, in terms of increasing the proportion of eyes that remain relapse free and do not require external beam radiotherapy and/or enucleation, in patients with newly diagnosed Group B, C, or D bilateral intraocular retinoblastoma.

Secondary

• Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive high-dose carboplatin IV over 30 minutes on day 1; vincristine IV over 5 minutes and high-dose etoposide IV over 25 minutes on day 2; cyclosporine IV over 1 hour before chemotherapy and then over 2 hours after chemotherapy on days 1 and 2, and filgrastim (G-CSF) subcutaneously once daily beginning on day 3 and continuing until day 16 or until blood counts recover. Treatment repeats every 21 days for a total of 3 courses for patients with Group B disease and a total of 6 courses for patients with Group C or D disease.

Patients undergo eye examination under anesthesia (EUA) at initial staging and then before each course of chemotherapy. Patients with small peripheral tumors in eyes without retinal detachment undergo minimal focal therapy (mainly cryotherapy) during EUA at initial staging and then after chemotherapy courses 1 and 2. At EUA after the third and subsequent courses of chemotherapy, patients with tumors that have sufficiently reduced in size undergo additional cryotherapy or laser therapy. After completion of chemotherapy, patients with any suspicious, active, or reactivated tumor undergo additional cryotherapy and/or laser therapy during EUA approximately every 4-8 weeks (or at longer intervals) for up to 5 years (as needed).

After completion of study chemotherapy, patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually for 1 year.

PROJECTED ACCRUAL: A total of 71 patients will be accrued for this study within 2.4 years.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Clinical diagnosis of bilateral intraocular retinoblastoma (RB)
• International Intraocular Retinoblastoma Classification (IIRC) Group B, C, or D disease in 1 or both eyes
• IIRC Group E disease in 1 eye allowed provided the eye was enucleated at diagnosis AND there is no extraocular RB in the enucleated eye by histologic confirmation AND there is IIRC Group B, C, or D disease in the remaining eye
• No IIRC Group A disease in 1 or both eyes
• No unilateral RB
• No extraocular or metastatic RB

PATIENT CHARACTERISTICS: Age

• Over 30 days

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• AST and ALT < 2 times upper limit of normal (ULN)
• Conjugated and unconjugated bilirubin < 2 times ULN

Renal

• Creatinine < 1.5 times ULN
• Glomerular filtration rate (GFR) ≥ 100 mL/min* NOTE: *A 4-hour IV hydration is allowed if GFR is low due to poor hydration or transient dehydration

Other

• Meets 1 of the following auditory criteria:
• Normal audiogram
• At least normal responses to speech by audiogram
• Documentation of hearing by acoustic emission test
• Recording of evoked potentials by auditory brain stem response

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• See Disease Characteristics

Please refer to this study by ClinicalTrials.gov identifier  NCT00110110

Canada, Ontario
      Hospital for Sick Children, Toronto,  Ontario,  M5G 1X8,  Canada; Recruiting

Study chairs or principal investigators

Helen S.L. Chan, MD,  Study Chair,  The Hospital for Sick Children   

Study ID Numbers:  CDR0000422340; HFSC-OCRN-RB-2003
Record last reviewed:  April 2005
Last Updated:  May 3, 2005
Record first received:  May 3, 2005
ClinicalTrials.gov Identifier:  NCT00110110
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-05-17