Combination Chemotherapy and Cyclosporine Followed by Focal Therapy for Bilateral Retinoblastoma

NCT00110110 | Active Not Recruiting Phase 2 DMC

• 3 other identifiers: 1000005587HFSC-OCRN-RB-2003CDR0000422340
• Study Type: interventional
• Target: 71
• Locations: 4 countries
• Sites: 6

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.

Conditions

Retinoblastoma

Keywords

intraocular retinoblastoma

Outcome Measures

Primary Outcomes (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

  Efficacy

  5 year follow-up per patient

Secondary Outcomes (1)

• Toxicity during treatment

  5 year follow-up per patient

Study Arms (1)

CEV Chemo + Cyclosporine & Focal Therapy

EXPERIMENTAL

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; Drug: Carboplatin; Drug: Cyclosporine; Drug: Etoposide; Drug: vincristine sulfate; Procedure: cryosurgery; Procedure: laser therapy

Interventions

filgrastim BIOLOGICAL

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

Also known as: granulocyte colony-stimulating factor (G-CSF)

CEV Chemo + Cyclosporine & Focal Therapy

Carboplatin DRUG

Given at 28 mg/kg/dose.

CEV Chemo + Cyclosporine & Focal Therapy

Cyclosporine DRUG

Given at 33 mg/kg/dose

CEV Chemo + Cyclosporine & Focal Therapy

Etoposide DRUG

Given at 12 mg/kg/dose

CEV Chemo + Cyclosporine & Focal Therapy

vincristine sulfate 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

Also known as: vincristine

CEV Chemo + Cyclosporine & Focal Therapy

cryosurgery PROCEDURE

Local application of extreme cold to destroy residual tumor.

Also known as: cryotherapy

CEV Chemo + Cyclosporine & Focal Therapy

laser therapy PROCEDURE

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

CEV Chemo + Cyclosporine & Focal Therapy

Eligibility Criteria

• Age: 30 Days+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• The Hospital for Sick Children: lead
• Terry Fox Foundation: collaborator

Study Sites (6)

Children's and Women's Hospital of British Columbia

Vancouver, British Columbia, V6H 3V4, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Montreal Children's Hospital at McGill University Health Center

Montreal, Quebec, H3H 1P3, Canada

Location

Hospital San Juan de Dios

Santiago, 8500000, Chile

Location

Sankara Nethralaya Super Specialty Clinic

Chennai, 600 006, India

Location

Kandang Kerbau Women's and Children's Hospital

Singapore, 229899, Singapore

Location

MeSH Terms

Conditions

Retinoblastoma

Interventions

Filgrastim; Granulocyte Colony-Stimulating Factor; Carboplatin; Cyclosporine; Etoposide; Vincristine; Cryosurgery; Cryotherapy; Laser Therapy

Condition Hierarchy (Ancestors)

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, Hereditary; Eye Diseases; Retinal Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Coordination Complexes; Organic Chemicals; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Glucosides; Glycosides; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Ablation Techniques; Surgical Procedures, Operative; Therapeutics

Study Officials

• Brenda L Gallie, MD

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

• Elise Heon, MD

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

• Helen SL Chan, MD, BS

  The Hospital for Sick Children

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Oncologist

Study Record Dates

• First Submitted: May 3, 2005
• First Posted: May 4, 2005
• Study Start: June 1, 2004
• Primary Completion: April 20, 2016
• Study Completion: December 31, 2024
• Last Updated: April 17, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CL (1); IN (1); CA (3); SG (1)