Combination Chemotherapy and Cyclosporine Followed by Focal Therapy for Bilateral Retinoblastoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by The Hospital for Sick Children
Sponsor:
Collaborator:
Terry Fox Foundation
Information provided by (Responsible Party):
Helen Chan, The Hospital for Sick Children
ClinicalTrials.gov Identifier:
NCT00110110
First received: May 3, 2005
Last updated: May 29, 2013
Last verified: May 2013
  Purpose

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 Intervention Phase
Retinoblastoma
Biological: filgrastim
Drug: carboplatin
Drug: cyclosporine
Drug: etoposide
Drug: vincristine sulfate
Procedure: cryosurgery
Procedure: laser therapy
Procedure: neoadjuvant therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by The Hospital for Sick Children:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity during treatment [ Time Frame: 5 year follow-up per patient ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 71
Study Start Date: June 2004
Estimated Study Completion Date: November 2020
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combination Chemotherapy with Cyclosporine and Focal Therapy Biological: filgrastim Drug: carboplatin Drug: cyclosporine Drug: etoposide Drug: vincristine sulfate Procedure: cryosurgery Procedure: laser therapy Procedure: neoadjuvant therapy

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00110110

Contacts
Contact: Helen Chan helen.chan@sickkids.ca

Locations
Canada, British Columbia
Children's and Women's Hospital of British Columbia Recruiting
Vancouver, British Columbia, Canada, V6H 3V4
Contact: Caron Strahlendorf, MD, MBBCH, FCP    604-875-3576    cstrahlendorf@cw.bc.ca   
Canada, Ontario
Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Helen S. L. Chan, MD, BS, FRCPC, FAAP    416-813-5040    helen.chan@sickkids.ca   
Principal Investigator: Brenda L Gallie, MD         
Sub-Investigator: Elise Heon, MD         
Canada, Quebec
Montreal Children's Hospital at McGill University Health Center Recruiting
Montreal, Quebec, Canada, H3H 1P3
Contact: Anne-Sophie Carret, MD    514-412-4400 ext. 23190      
Chile
Hospital San Juan de Dios Recruiting
Santiago de Chile, Chile, 8500000
Contact: Diego Ossandon, MD    56-2574-2103      
India
Sankara Nethralaya Super Specialty Clinic Recruiting
Chennai, India, 600 006
Contact: Vikas Khetan, MD    91-44-4205-9780      
Singapore
Kandang Kerbau Women's and Children's Hospital Recruiting
Singapore, Singapore, 229899
Contact: Ah M. Tan, MD    65-6293-4044      
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

Additional Information:
No publications provided

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, CDR0000422340
Study First Received: May 3, 2005
Last Updated: May 29, 2013
Health Authority: Canada: Health Canada

Keywords provided by 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
Cyclosporins
Cyclosporine
Lenograstim
Etoposide
Vincristine
Etoposide phosphate
Carboplatin
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents

ClinicalTrials.gov processed this record on July 28, 2014