Brief Title
Intra-arterial Chemotherapy With Melphalan for the Treatment of Retinoblastoma (RTB) in Advanced Intraocular Stage
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
Brief Summary
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.
Detailed Description
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
To assess the saving of eyes affected with RTB for patients who would have been candidates for enucleation.
Secondary Outcome
To preserve visual acuity, by studying the affected eye after the third cycle of treatment.
Condition
Retinoblastoma
Intervention
Melphalan
Study Arms / Comparison Groups
Melphalan
Description: 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).
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
5
Start Date
November 2009
Completion Date
May 2013
Primary Completion Date
December 2012
Eligibility Criteria
Inclusion Criteria:
1. Patients with unilateral RTB.
2. Patients with advanced intraocular involvement, corresponding to Stage D of the
International Classification , selected by the Tumour Committee of the Retinoblastoma
Unit.
By contrast to most other cancers, histological confirmation is contraindicated in RTB
prior to onset of treatment and, in our study, any biopsy of the tumour practiced was
considered as an exclusion criterion.
3. The only alternative to treatment is enucleation.
4. Over six months old at diagnosis and younger than six years old.
5. Informed consent of the parents or legal representative.
Exclusion Criteria:
1. Under 6 months old at diagnosis.
2. Impaired kidney function, with creatinine clearance lower than 80 mL/min/1.73m2 or
serum creatinine higher than 0.7 mg/dL.
3. Impaired liver function, normal function being defined as presenting total bilirubin
levels lower than 1.5 times the limit of normal for that age and ALT lower than 5
times the limit of normal for that age.
4. Patients with some type of coagulation disorder that could contraindicate the
procedure or with a previous diagnosis of any thrombotic condition.
5. Congenital cerebral anomalies diagnosed previously or detected by angioresonance prior
to treatment for extraocular involvement by RTB shown by image techniques,
cerebrospinal fluid (CSF) cytology or cytomorphology of bone marrow aspirates (BMA),
or positive expression of GD2 synthase in CSF or BMA.
6. Patients with heart disease, arterial hypertension, or diseases of the nervous system
not referred to in point 5, or with active infections that the Anaesthesiology Service
responsible for the procedure have studied and consider to contraindicate the
procedure.
7. Not having been selected for intra-arterial chemotherapy through the ophthalmic artery
for any other reason than those given by the Tumour Committee of the RTB Unit of the
HSJD.
8. Concurrent administration of any other anti-cancer treatment.
9. Any surgical or non-surgical procedure that could have changed the structure of the
eye and, therefore, facilitate risk of dissemination, including histological
confirmation prior to treatment.
10. Participation in another clinical trial.
Gender
All
Ages
6 Months - 6 Years
Accepts Healthy Volunteers
No
Contacts
Andreu Parareda, MD, ,
Location Countries
Spain
Location Countries
Spain
Administrative Informations
NCT ID
NCT01393769
Organization ID
HSJD-RTB-QTIA
Secondary IDs
2009-010737-47
Responsible Party
Sponsor
Study Sponsor
Hospital Sant Joan de Deu
Collaborators
Fundació Sant Joan de Déu
Study Sponsor
Andreu Parareda, MD, Principal Investigator, Hospital Sant Joan de Deu
Verification Date
August 2016