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 17, 2018
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|
- 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.
- 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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||71 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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)|
|Actual Study Start Date :||June 2004|
|Actual Primary Completion Date :||April 20, 2016|
|Estimated Study Completion Date :||December 2019|
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.
Given after chemo cycle for 7 days or until neutrophil counts return to normal.
Other Name: granulocyte colony-stimulating factor (G-CSF)
Given at 28 mg/kg/dose.
Given at 33 mg/kg/dose
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
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.
- 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
- Toxicity during treatment [ Time Frame: 5 year follow-up per patient ]Toxicity
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
|Canada, British Columbia|
|Children's and Women's Hospital of British Columbia|
|Vancouver, British Columbia, Canada, V6H 3V4|
|Hospital for Sick Children|
|Toronto, Ontario, Canada, M5G 1X8|
|Montreal Children's Hospital at McGill University Health Center|
|Montreal, Quebec, Canada, H3H 1P3|
|Hospital San Juan de Dios|
|Santiago, Chile, 8500000|
|Sankara Nethralaya Super Specialty Clinic|
|Chennai, India, 600 006|
|Kandang Kerbau Women's and Children's Hospital|
|Singapore, Singapore, 229899|
|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|