Study of Treatment for Patients With Cancer of the Eye -Retinoblastoma
Overview[ - collapse ][ - ]
| Purpose | Retinoblastoma is a childhood cancer which affects the retina of the eye. The retina is the light sensitive layer of tissue that lines the back of the eyeball; sends visual messages through the optic nerve to the brain. When only one eye is affected, this is known as unilateral retinoblastoma and when both eyes are affected, it is called bilateral retinoblastoma. Treatment for retinoblastoma is individualized for each patient and is based on the form and the stage of the disease (inside the eye or has moved outside). The main goal is always to cure the cancer, and save the life of the child. Treatments are also designed with the hope of saving the vision, while completely destroying the tumor. Therapies may involve surgery, chemotherapy, radiation, and other treatments called focal treatments. Focal treatments may be laser therapy, freezing, or heat treatments meant to shrink and kill the tumor. In this study, researchers want to investigate how different participants respond to different therapies that are individualized specifically for them. Participants will be divided into three main groups, depending on whether the disease is unilateral or bilateral, and the stage of the disease. One of the main objectives of the study is to investigate how advanced tumors in children with bilateral disease respond to a new combination of chemotherapy with topotecan and vincristine, with G-CSF support. In order to improve results, some children with very advanced disease may receive carboplatin chemotherapy given around the eye at the same time that they receive topotecan by vein. Also, because children with retinoblastoma are diagnosed so early in life and the vision may be significantly impaired, this study will investigate how children develop and how the brain adjusts and compensates for the visual deficits. Finally, this study also investigates the biology of retinoblastoma, in order to understand better how this cancer develops. |
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| Condition | Retinoblastoma Retinal Neoplasm |
| Intervention | Procedure: Enucleation Drug: Vincristine, Carboplatin Procedure: Focal Therapies Radiation: External Beam Radiation Drug: Vincristine + Topotecan Drug: Vincristine + Carboplatin + Etoposide Drug: Vincristine + Cyclophosphamide + Doxorubicin Drug: Vincristine+Carboplatin+Etoposide Procedure: Periocular carboplatin Other: G-CSF |
| Phase | Phase 3 |
| Sponsor | St. Jude Children's Research Hospital |
| Responsible Party | St. Jude Children's Research Hospital |
| ClinicalTrials.gov Identifier | NCT00186888 |
| First Received | September 12, 2005 |
| Last Updated | June 12, 2013 |
| Last verified | June 2013 |
Tracking Information[ + expand ][ + ]
| First Received Date | September 12, 2005 |
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| Last Updated Date | June 12, 2013 |
| Start Date | February 2005 |
| Estimated Primary Completion Date | November 2016 |
| Current Primary Outcome Measures | Stratum B Response to Window Therapy [Time Frame: Six weeks post window therapy] [Designated as safety issue: No]The primary outcome is to estimate the proportion of stratum B patients responding to 2 courses of window therapy consisting of vincristine and topotecan. Complete Response is the complete regression of all apparent tumor masses in the funduscopic examination and by MRI and ultrasound (US). Partial Response is defined as greater than 50% (but less than 100%) reduction of the tumor masses in the funduscopic examination and by US and MRI, without the appearance of any new lesions. The response must persist for at least 4 weeks. Stratum A and C did not receive window therapy. |
| Current Secondary Outcome Measures |
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Descriptive Information[ + expand ][ + ]
| Brief Title | Study of Treatment for Patients With Cancer of the Eye -Retinoblastoma |
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| Official Title | Protocol for the Study and Treatment of Patients With Intraocular Retinoblastoma |
| Brief Summary | Retinoblastoma is a childhood cancer which affects the retina of the eye. The retina is the light sensitive layer of tissue that lines the back of the eyeball; sends visual messages through the optic nerve to the brain. When only one eye is affected, this is known as unilateral retinoblastoma and when both eyes are affected, it is called bilateral retinoblastoma. Treatment for retinoblastoma is individualized for each patient and is based on the form and the stage of the disease (inside the eye or has moved outside). The main goal is always to cure the cancer, and save the life of the child. Treatments are also designed with the hope of saving the vision, while completely destroying the tumor. Therapies may involve surgery, chemotherapy, radiation, and other treatments called focal treatments. Focal treatments may be laser therapy, freezing, or heat treatments meant to shrink and kill the tumor. In this study, researchers want to investigate how different participants respond to different therapies that are individualized specifically for them. Participants will be divided into three main groups, depending on whether the disease is unilateral or bilateral, and the stage of the disease. One of the main objectives of the study is to investigate how advanced tumors in children with bilateral disease respond to a new combination of chemotherapy with topotecan and vincristine, with G-CSF support. In order to improve results, some children with very advanced disease may receive carboplatin chemotherapy given around the eye at the same time that they receive topotecan by vein. Also, because children with retinoblastoma are diagnosed so early in life and the vision may be significantly impaired, this study will investigate how children develop and how the brain adjusts and compensates for the visual deficits. Finally, this study also investigates the biology of retinoblastoma, in order to understand better how this cancer develops. |
| Detailed Description | This study will determine the following: 1. To estimate the ocular survival and event-free survival of bilateral disease patients with advanced intraocular retinoblastoma in either eye (R-E IV-V) responding to the vincristine/topotecan window, with alternating cycles of vincristine and carboplatin with vincristine, topotecan, and periocular carboplatin, with intensive focal treatments. 2. To estimate the ocular survival of eye and event-free survival of eye of bilateral disease patients with advanced intraocular retinoblastoma in either eye (R-E IV-V) responding to the vincristine/topotecan window, with alternating cycles of vincristine and carboplatin with vincristine, topotecan, and periocular carboplatin, with intensive focal treatments. 3. To estimate the ocular survival and event free survival of patients with advanced intraocular retinoblastoma (R-E IV-V) not responding to the vincristine/topotecan window, with a combination of vincristine, carboplatin, etoposide, and periocular carboplatin, with intensive focal treatments. 4. To estimate the ocular survival and event free survival of eye of patients with advanced intraocular retinoblastoma (R-E IV-V) not responding to the vincristine/topotecan window, with a combination of vincristine, carboplatin, etoposide, and periocular carboplatin, with intensive focal treatments. 5. To estimate the ocular survival and event-free survival of patients with early stage intraocular retinoblastoma (R-E I-III) with vincristine and carboplatin with intensive focal treatments. 6. To estimate the ocular survival of eye and event-free survival of eye of patients with early stage intraocular retinoblastoma (R-E I-III) with vincristine and carboplatin with intensive focal treatments. 7. To estimate the response rate of early stage eyes (R-E I-III) in patients with contralateral advanced disease treated with vincristine and topotecan. 8. To estimate the ocular survival and event-free survival of early stage eyes (R-E I-III) of patients with contralateral advanced disease treated with vincristine and topotecan. 9. To describe the outcome of intraocular retinoblastoma with respect to the new International Classification for Intraocular Retinoblastoma and the AJCC. 10. To describe primary visual cortex function in patients with unilateral and bilateral retinoblastoma. 11. To describe the cognitive, adaptive, and social/emotional development of children with retinoblastoma. 12. To describe changes in the pineal gland during treatment in patients with bilateral retinoblastoma. 13. To provide insight into molecular pathogenesis of retinoblastoma. 14. To describe the incidence and type of germline mutations of the RB gene in patients with retinoblastoma. 15. To assess the relation between CYP3A4/5 genotype and the pharmacokinetics and pharmacodynamics of topotecan. 16. To assess the relation between ABCG2 genotype and the pharmacokinetics and pharmacodynamics of topotecan. 17. To determine if carboplatin can produce changes in cochlear function that are detectable with measurement of otoacoustic emissions. 18. To evaluate the need for and feasibility of starting early intervention support during the first year after the diagnosis of retinoblastoma. |
| Study Type | Interventional |
| Study Phase | Phase 3 |
| Study Design | Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment |
| Condition |
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| Intervention | Procedure: Enucleation Enucleation (possibly associated with all treatment strata/arms. For Stratum A, patients with bilateral disease will have surgery to remove the advanced eye before chemotherapy, or patients that have disease progression after chemotherapy my have surgery to remove the affected eye. For Stratum B, Surgical removal of the affected eye may be required in cases of disease progression For Stratum C, first intervention is removal of the affected eye. Drug: Vincristine, Carboplatin (Stratum A subjects receive 8 courses every 3-4 weeks, Stratum B subjects receive this combination for Courses 3, 4, 6, 7, 9, and 10 after the window, if they respond to window therapy) Vincristine dosage< 12 months of age: 0.05 mg/kg i.v. day 1, ≥ 12 months of age: 1.5 mg/m2 i.v. day 1 (max. dose 2 mg) Carboplatin will be administered i.v. to achieve an AUC of 6.5 mg/ml/min, day 1. Procedure: Focal Therapies Method will be at the discretion of the treating team, used after second course of chemotherapy. Cryotherapy- freezing of affected tissue, Laser photocoagulation- using lasers to destroy affected tissue, Thermotherapy and thermochemotherapy- using heat or heat/chemotherapy combination to destroy diseased tissue, and Episcleral plaque brachytherapy- radiation insertions in the diseased area to destroy affected tissue. Radiation: External Beam Radiation 44-46 Gy administered using standard practices , limiting dose to normal tissues to subjects with recurrent or progressive disease not considered controllable with focal treatments, Stratum B subjects with suspected active disease after completing therapy, or patients considered to have high-risk disease. Drug: Vincristine + Topotecan (Stratum B subjects receive two up-front courses of vincristine and topotecan, given in 21-day intervals, then those who respond receive 3 additional courses (courses 5, 8, and 11) after the window. Dosages are the same for both window and subsequent courses: Vincristine: < 12 months of age: 0.05 mg/kg i.v. day 1, ≥ 12 months of age: 1.5 mg/m2 i.v. day 1 (max. dose 2 mg) Topotecan: TSE of 140 ± 20 ng/ml*hr, daily for 5 consecutive days, infused over 30 minutes. Drug: Vincristine + Carboplatin + Etoposide Stratum B patients that do not respond to window receive 6 courses of this combination. Vincristine: < 12 months of age: 0.05 mg/kg i.v. day 1, ≥ 12 months of age: 1.5 mg/m2 i.v. day 1 (max. dose 2 mg) Carboplatin will be administered i.v. to achieve an AUC of 6.5 mg/ml/min, day 1 Etoposide, < 12 months of age: 3.3 mg/kg/d i.v. days 1 - 3, ≥ 12 months of age: 100 mg/m2/d i.v. days 1 - 3 Drug: Vincristine + Cyclophosphamide + Doxorubicin (High risk Stratum C patients in courses 2, 4, and 6 after enucleation, intermediate risk stratum C patients for four consecutive courses after enucleation) Vincristine: < 12 months of age: 0.05 mg/kg i.v. day 1, ≥ 12 months of age: 1.5 mg/m2 i.v. day 1 (max. dose 2 mg) Cyclophosphamide: < 12 months of age: 40 mg/kg i.v. day 1, ≥ 12 months of age: 1,200 mg/m2 i.v. day 1, MESNA 200 mg/m2 at 0, 3, 6, and 9 hours Doxorubicin < 12 months of age: 1.5 mg/kg i.v. day 1, ≥ 12 months of age: 45 mg/m2 i.v. day 1 Drug: Vincristine+Carboplatin+Etoposide High risk Stratum C patients in courses 1, 3, and 5 after enucleation: Vincristine: < 12 months of age: 0.05 mg/kg i.v. day 1, ≥ 12 months of age: 1.5 mg/m2 i.v. day 1 (max. dose 2 mg) Carboplatin will be administered i.v. to achieve an AUC of 6.5 mg/ml/min, day 1 Etoposide, < 12 months of age: 3.3 mg/kg/d i.v. days 1 - 3, ≥ 12 months of age: 100 mg/m2/d i.v. days 1 - 3 Procedure: Periocular carboplatin Periocular (subtenon) carboplatin 20 mg, one injection, in courses 5, 8, and 11 in patients responding to the VT window, and in courses 1, 3, and 6 of VCE in patients not responding to the VT window, when active vitreous disease is present. Carboplatin 20 mg will be diluted in 2 mL of NS or D5W and given by subtenon administration while the patient is under general anesthesia. Other: G-CSF G-CSF (5 mcg/kg/day), will be administered starting 24-36 hours after the completion of each course of chemotherapy, for 7 to 10 days, until ANC is > 2,000/mL in one occasion after the expected nadir. |
| Study Arm (s) |
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Recruitment Information[ + expand ][ + ]
| Recruitment Status | Active, not recruiting |
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| Estimated Enrollment | 107 |
| Estimated Completion Date | November 2016 |
| Estimated Primary Completion Date | November 2013 |
| Eligibility Criteria | Inclusion Criteria: - Must have newly diagnosed intraocular retinoblastoma, previously untreated. Patients previously diagnosed with unilateral retinoblastoma treated surgically (or with focal therapies), who develop asynchronous involvement of the contralateral eye, will be eligible for study. - Must have a life expectancy of at least 8 weeks. - Must have Performance Status (ECOG) of 0-2. - Patients must have an adequate liver function, as defined by bilirubin less than or equal to 3 x normal, and SGOT and SGPT less than or equal to 3x normal. - Patients must have adequate renal function as defined by serum creatinine less than or equal to 3x normal for age. - Legal guardians must sign an informed consent indicating that they are aware of this study, its possible benefits, and toxic side effects. Legal guardians will be given a copy of the consent form. Exclusion Criteria: - Previously treated patients - Presence of metastatic disease or orbital involvement - Patients must not have an invasive infection at time of protocol entry. |
| Gender | Both |
| Ages | N/A |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | United States |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT00186888 |
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| Other Study ID Numbers | RET5 |
| Has Data Monitoring Committee | Yes |
| Information Provided By | St. Jude Children's Research Hospital |
| Study Sponsor | St. Jude Children's Research Hospital |
| Collaborators | National Cancer Institute (NCI) |
| Investigators | Principal Investigator: Ibrahim Qaddoumi, M.D. St. Jude Children's Research Hospital |
| Verification Date | June 2013 |
Locations[ + expand ][ + ]
| St. Jude Children's Research Hospital | Memphis, Tennessee, United States, 38105 |
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