Intra-arterial Chemotherapy With Melphalan for the Treatment of Retinoblastoma (RTB) in Advanced Intraocular Stage
For selected cases with advanced Retinoblastoma (RTB) intraocular involvement(stage V of the Reese-Ellsworth classification) in which enucleation would usually be the standard therapeutic approach, in this project the investigators propose an alternative conservative treatment using intra-arterial chemotherapy with melphalan, via direct administration by catheterization of the ophthalmic artery.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open, Single-centre Non-randomized Phase II Clinical Trial on Intra-arterial Chemotherapy With Melphalan for the Treatment of Retinoblastoma (RTB) in Advanced Intraocular Stage|
- To assess the saving of eyes affected with RTB for patients who would have been candidates for enucleation. [ Time Frame: From V1 (Baseline) to V14 (1+ year after last treatment) ] [ Designated as safety issue: No ]The primary endpoint will be the objective response to treatment determined by funduscopy and RetCam explorations, recorded as a percentage of partial response (PR) or complete response (CR) to the treatment administered.
- The response will be evaluated as a function of tumoral volumetric size. [ Time Frame: From V1 (Baseline) to V14 (+1 year after last treatment) ] [ Designated as safety issue: No ]The response will be evaluated as a function of tumoral volumetric size by comparing images obtained in successive funduscopy and RetCam explorations.
- To preserve visual acuity, by studying the affected eye after the third cycle of treatment. [ Time Frame: V1 (Basal), V13 (day +52 to +60), V14 (+1 year after last treatment) ] [ Designated as safety issue: No ]The secondary endpoint studied will correspond to changes in visual acuity of the affected eye after the third cycle of treatment, assessed by a visual acuity study.
- To modify the result of electroretinographic studies and visual evoked potentials after the third cycle of treatment. [ Time Frame: V1 (Basal), V13 (day +52 to +60), V14 (+1 year after last treatment dosage) ] [ Designated as safety issue: No ]The secondary endpoint studied will correspond to changes in electroretinographic studies and visual evoked potentials after the third cycle of treatment
- To evaluate the safety of the technique and medicinal product used, by studying the ophthalmologic and systemic adverse events. [ Time Frame: Adverse events:on ongoing basis-assessed in each protocol visit / Laboratory test: V1 (Basal), V3&4 (day +1 to+10), V7&8 (day +22 to +31), V11&12 (day +43 to +52) ] [ Designated as safety issue: Yes ]The secondary safety endpoints studied will correspond to analytical changes in the CBC (essentially in the number of absolute neutrophils) and biochemistry analysis after 10 days of each treatment, and potential ophthalmologic side effects.
|Study Start Date:||November 2009|
|Estimated Study Completion Date:||December 2012|
|Estimated Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Intra-arterial chemotherapy with melphalan, via direct administration by catheterization of the ophthalmic artery. Dosage range from 3 to 5 mg, depending of patient's weight and estimated tumour volume: a)3 mg for patients under 10 kg and tumour volume size under 1,5 cm3; b)5 mg for patients over 10 kg and tumour volume over 1,5 cm3; c)4 mg in all other situations(tumour volume over 1,5 cm3 in patients under 10 kg or tumour volume under 1,5 cm3 in patients over 10 kg).
The usual number of chemotherapy cycles will be 3. First treatment with Melphalan will be initiated as soon as possible, once the patients are selected for the study. Once the first treatment has been completed, day 0, successive treatments will be considered, second and third (days 21 and 42). In those cases in which some patients could be considered for an additional treatments after the third cycle, these will be administrated in intervals at least of 21 days.Dosage range from 3 to 5 mg, depending of patient's weight and estimated tumour volume.
Retinoblastoma (RTB) is the most frequent tumour of the eye in early childhood and the commonest cancer in the first year of life. Approximately 60% of cases are sporadic and unilateral. Unilateral tumours are usually diagnosed in the advanced intraocular stage and the most frequent treatment prescribed is enucleation. This prevents disease progression but has an important visual risk, and also constitutes a mutilation, with potentially devastating psychological effects on patients and their relatives.
At diagnosis, patients affected with RTB and their relatives are faced with the important effects of this disease, such as a threat to life, although rare in developed countries, and the risk of losing their sight, which depends on the uni- or bilateral nature of the tumour, the topography of the tumour or tumours, and the still prevalent need for enucleation as a treatment. In fact, almost all advanced stage unilateral RTBs are treated with enucleation. In addition to the risk to life and the patient's sight associated with this treatment, it is also important to take into account the risk to the eye itself. For selected cases with advanced intraocular involvement (stage V of the Reese-Ellsworth classification) in which enucleation would usually be the standard therapeutic approach, in this project we propose an alternative conservative treatment using intra-arterial chemotherapy with melphalan, via direct administration by catheterization of the ophthalmic artery.
The treatment aims to preserve the eye ball and visual acuity as much as possible in these patients, and has been demonstrated to be extremely effective at achieving volumetric reduction of tumours, which permits, if necessary, the subsequent conservative treatment, mainly with brachytherapy for anterior tumours or thermotherapy with laser diode for posterior tumours. In cases of retinal detachment, significant volume reduction, such as that achieved after injection with melphalan would, in most cases, permit retinal reapplication that would favour visual prognosis.
This technique was first described by David H. Abramson in the Sloan-Kettering Cancer Center Memorial Hospital of New York (A Phase I/II Study of direct Intra-arterial (Ophthalmic Artery) Chemotherapy with Melphalan for Intraocular Retinoblastoma). Here, in this study we propose using this technique for the first time outside New York city, in our own clinical setting (Retinoblastoma Unit, affiliated to the Oncology Development Department and the Ophthalmology Department of the Sant Joan de Déu Hospital in Barcelona).
The attainment of positive results, in addition to those previously obtained by the New York project, could consolidate this treatment as an alternative to enucleation in most cases of advanced intraocular RTB, and open the way for the future indication of this technique in other stages of RTB.
|Contact: Andreu Parareda, MD||+34 93 280 40 email@example.com|
|Hospital Sant Joan de Déu||Recruiting|
|Esplugues de Llobregat, Barcelona, Spain, 08950|
|Contact: Andreu Parareda, MD +34 93 280 40 00 firstname.lastname@example.org|
|Sub-Investigator: Joan Prat, MD|
|Sub-Investigator: Jaume Català, MD|
|Sub-Investigator: Jaume Mora, MD|
|Sub-Investigator: Ofelia Cruz, MD|
|Sub-Investigator: Leopoldo Guimaraens, MD|
|Sub-Investigator: Teresa Sola, MD|
|Sub-Investigator: Joan Vinent, Mr|
|Sub-Investigator: Alexandra Álvarez, Mrs.|
|Principal Investigator:||Andreu Parareda, MD||Hospital Sant Joan de Déu|