Intra-arterial Chemotherapy With Melphalan for the Treatment of Retinoblastoma (RTB) in Advanced Intraocular Stage

NCT01393769 | Terminated Phase 2

• 2 other identifiers: HSJD-RTB-QTIA2009-010737-47
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Retinoblastoma

Keywords

Retinoblastoma; RTB; Ocular tumour; Melfalan; Enucleation; Tumor of the eye; Eye; Ocular cancer; Ocular chemotherapy; Ophthalmic artery; Intra-arterial chemotherapy

Outcome Measures

Primary Outcomes (2)

• To assess the saving of eyes affected with RTB for patients who would have been candidates for enucleation.

  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.

  From V1 (Baseline) to V14 (1+ year after last treatment)

• The response will be evaluated as a function of tumoral volumetric size.

  The response will be evaluated as a function of tumoral volumetric size by comparing images obtained in successive funduscopy and RetCam explorations.

  From V1 (Baseline) to V14 (+1 year after last treatment)

Secondary Outcomes (3)

• To preserve visual acuity, by studying the affected eye after the third cycle of treatment.

  V1 (Basal), V13 (day +52 to +60), V14 (+1 year after last treatment)

• To modify the result of electroretinographic studies and visual evoked potentials after the third cycle of treatment.

  V1 (Basal), V13 (day +52 to +60), V14 (+1 year after last treatment dosage)

• To evaluate the safety of the technique and medicinal product used, by studying the ophthalmologic and systemic adverse events.

  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)

Study Arms (1)

Melphalan

EXPERIMENTAL

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).

Drug: Melphalan

Interventions

Melphalan DRUG

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.

Also known as: Melfalan, Melfalan GlaxoSmithKline Inyectable

Melphalan

Eligibility Criteria

• Age: 6 Months - 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Patients with unilateral RTB.
• Patients with advanced intraocular involvement, corresponding to Stage D of the International Classification , selected by the Tumour Committee of the Retinoblastoma Unit.
• The only alternative to treatment is enucleation.
• Over six months old at diagnosis and younger than six years old.
• Informed consent of the parents or legal representative.

You may not qualify if:

• Under 6 months old at diagnosis.
• Impaired kidney function, with creatinine clearance lower than 80 mL/min/1.73m2 or serum creatinine higher than 0.7 mg/dL.
• 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.
• Patients with some type of coagulation disorder that could contraindicate the procedure or with a previous diagnosis of any thrombotic condition.
• 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.
• 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.
• 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.
• Concurrent administration of any other anti-cancer treatment.
• 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.
• Participation in another clinical trial.

Sponsors & Collaborators

• Hospital Sant Joan de Deu: lead
• Fundació Sant Joan de Déu: collaborator
• Hospital Universitari General de Catalunya: collaborator
• Ministry of Health, Spain: collaborator

Study Sites (1)

Hospital Sant Joan de Déu

Esplugues de Llobregat, Barcelona, 08950, Spain

Location

Related Publications (21)

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  PMID: 2774035 BACKGROUND

• Muen WJ, Kingston JE, Robertson F, Brew S, Sagoo MS, Reddy MA. Efficacy and complications of super-selective intra-ophthalmic artery melphalan for the treatment of refractory retinoblastoma. Ophthalmology. 2012 Mar;119(3):611-6. doi: 10.1016/j.ophtha.2011.08.045. Epub 2011 Dec 22.

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MeSH Terms

Conditions

Retinoblastoma; Eye Neoplasms

Interventions

Melphalan

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; Neoplasms by Site; Eye Diseases, Hereditary; Eye Diseases; Retinal Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Andreu Parareda, MD

  Hospital Sant Joan de Deu

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2011
• First Posted: July 13, 2011
• Study Start: November 1, 2009
• Primary Completion: December 1, 2012
• Study Completion: May 1, 2013
• Last Updated: August 2, 2016

Record last verified: 2016-08

Locations

ES (1)