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Combination Chemotherapy and Cyclosporine Followed by Focal Therapy for Bilateral Retinoblastoma

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ClinicalTrials.gov Identifier: NCT00110110
Recruitment Status : Active, not recruiting
First Posted : May 4, 2005
Last Update Posted : April 25, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
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.


Condition or disease Intervention/treatment Phase
Retinoblastoma Biological: filgrastim Drug: Carboplatin Drug: Cyclosporine Drug: Etoposide Drug: vincristine sulfate Procedure: cryosurgery Procedure: laser therapy Phase 2

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.


Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 71 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multicenter Phase II Study for International Intraocular Retinoblastoma Classification Groups B, C & D Tumors Treated With Carboplatin-Etoposide-Vincristine-Cyclosporine-Focal Therapy Multimodality Protocol (OCRN Multicenter RB 2003)
Study Start Date : June 2004
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: 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.
Biological: filgrastim
Given after chemo cycle for 7 days or until neutrophil counts return to normal.
Other Name: granulocyte colony-stimulating factor (G-CSF)
Drug: Carboplatin
Given at 28 mg/kg/dose.
Drug: Cyclosporine
Given at 33 mg/kg/dose
Drug: Etoposide
Given at 12 mg/kg/dose
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
Other Name: vincristine
Procedure: cryosurgery
Local application of extreme cold to destroy residual tumor.
Other Name: cryotherapy
Procedure: laser therapy
Local and precise application of laser beams to destroy residual tumor.


Outcome Measures

Primary Outcome Measures :
  1. Comparing efficacy of study treatment with historic world data, in terms of increasing the proportion of eyes that remains relapse-free while avoiding external beam radiation and/or enucleation [ Time Frame: 5 year follow-up per patient ]
    Efficacy


Secondary Outcome Measures :
  1. Toxicity during treatment [ Time Frame: 5 year follow-up per patient ]
    Toxicity


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00110110


Locations
Canada, British Columbia
Children's and Women's Hospital of British Columbia
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Canada, Quebec
Montreal Children's Hospital at McGill University Health Center
Montreal, Quebec, Canada, H3H 1P3
Chile
Hospital San Juan de Dios
Santiago, Chile, 8500000
India
Sankara Nethralaya Super Specialty Clinic
Chennai, India, 600 006
Singapore
Kandang Kerbau Women's and Children's Hospital
Singapore, Singapore, 229899
Sponsors and Collaborators
The Hospital for Sick Children
Terry Fox Foundation
Investigators
Principal Investigator: Brenda L Gallie, MD The Hospital for Sick Children
Principal Investigator: Elise Heon, MD The Hospital for Sick Children
Study Chair: Helen SL Chan, MD, BS The Hospital for Sick Children
More Information

Responsible Party: Helen Chan, Oncologist, The Hospital for Sick Children
ClinicalTrials.gov Identifier: NCT00110110     History of Changes
Other Study ID Numbers: 1000005587
HFSC-OCRN-RB-2003 ( Other Identifier: The Hospital for Sick Children )
CDR0000422340 ( Other Identifier: The Hospital for Sick Children )
First Posted: May 4, 2005    Key Record Dates
Last Update Posted: April 25, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Helen Chan, The Hospital for Sick Children:
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 phosphate
Carboplatin
Etoposide
Vincristine
Cyclosporins
Cyclosporine
Lenograstim
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents