Combination Chemotherapy and Cyclosporine Followed by Focal Therapy for Bilateral Retinoblastoma

NCT ID: NCT00110110

Last Updated: 2024-04-17

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-06-30
• Study Completion Date: 2024-12-31

Brief Summary

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.

Detailed Description

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.

Conditions

Retinoblastoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CEV Chemo + Cyclosporine & Focal Therapy

Systemic carboplatin (28 mg/kg/dose), etoposide (12 mg/kg/dose) and vincristine sulfate (0.025 mg/kg/dose for the first cycle and 0.05 mg/kg/dose for subsequent cycles if first cycle well-tolerated) chemotherapy given with cyclosporin A (33 mg/kg/dose). Following 4-6 cycles CEV chemotherapy (depending on tumor stage) given every 3 weeks, focal laser therapy and/or cryosurgery are applied for tumor consolidation. Filgrastim is given after each chemotherapy cycle to prevent severe neutropenia.

Group Type: EXPERIMENTAL

filgrastim

Intervention Type: BIOLOGICAL

Given after chemo cycle for 7 days or until neutrophil counts return to normal.

Carboplatin

Intervention Type: DRUG

Given at 28 mg/kg/dose.

Cyclosporine

Intervention Type: DRUG

Given at 33 mg/kg/dose

Etoposide

Intervention Type: DRUG

Given at 12 mg/kg/dose

vincristine sulfate

Intervention Type: DRUG

Given at 0.025 mg/kg/dose for the first cycle and 0.05 mg/kg/dose for subsequent cycles if first cycle well-tolerated

cryosurgery

Intervention Type: PROCEDURE

Local application of extreme cold to destroy residual tumor.

laser therapy

Intervention Type: PROCEDURE

Local and precise application of laser beams to destroy residual tumor.

Interventions

filgrastim

Given after chemo cycle for 7 days or until neutrophil counts return to normal.

Intervention Type: BIOLOGICAL

Carboplatin

Given at 28 mg/kg/dose.

Intervention Type: DRUG

Cyclosporine

Given at 33 mg/kg/dose

Intervention Type: DRUG

Etoposide

Given at 12 mg/kg/dose

Intervention Type: DRUG

vincristine sulfate

Given at 0.025 mg/kg/dose for the first cycle and 0.05 mg/kg/dose for subsequent cycles if first cycle well-tolerated

Intervention Type: DRUG

cryosurgery

Local application of extreme cold to destroy residual tumor.

Intervention Type: PROCEDURE

laser therapy

Local and precise application of laser beams to destroy residual tumor.

Intervention Type: PROCEDURE

Other Intervention Names

granulocyte colony-stimulating factor (G-CSF); vincristine; cryotherapy

Eligibility Criteria

Inclusion 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

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

Exclusion Criteria

• IIRC Group A disease in 1 or both eyes
• unilateral RB
• extraocular or metastatic RB
• younger than 30 days
• Glomerular filtration rate (GFR) < 100 mL/min

• Minimum Eligible Age: 30 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Terry Fox Foundation

OTHER

Sponsor Role: collaborator

The Hospital for Sick Children

OTHER

Sponsor Role: lead

Responsible Party

Helen Chan

Oncologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Brenda L Gallie, MD

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children

Elise Heon, MD

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children

Helen SL Chan, MD, BS

Role: STUDY_CHAIR

The Hospital for Sick Children

Locations

Children's and Women's Hospital of British Columbia

Vancouver, British Columbia, Canada

Hospital for Sick Children

Toronto, Ontario, Canada

Montreal Children's Hospital at McGill University Health Center

Montreal, Quebec, Canada

Hospital San Juan de Dios

Santiago, , Chile

Sankara Nethralaya Super Specialty Clinic

Chennai, , India

Kandang Kerbau Women's and Children's Hospital

Singapore, , Singapore

Countries

Canada; Chile; India; Singapore

Other Identifiers

HFSC-OCRN-RB-2003

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000422340

Identifier Type: OTHER

Identifier Source: secondary_id

1000005587

Identifier Type: -

Identifier Source: org_study_id