Clinical trial NCT02866136: Conservative Treatments of Retinoblastoma
Official title: Conservative Treatments of Retinoblastoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Retinoblastoma
Children
Retinal Neoplasm
Lead sponsor: Institut Curie
Sponsor class: OTHER
Collaborators: name: Fondation Rothschild Paris
First posted: 2016-08-15
Enrollment: 133
Sex: ALL
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Conservative treatments of retinoblastoma (RETINO 2011)

1. -Multicentric non randomised, phase II study for the patients treated by chemoreduction (VP16, carboplatin) followed by chemothermotherapy without laser treatment at day 8
2. -Multicentric non randomised, phase II study for the patients with bilateral very asymmetric dis-ease (Group D eye on one of the eye) or unilateral presentation groups B/C/D according to the age and vitreous seeding
3. - Multicentric non randomised, phase II study for the patients treated by 6 cycles of three drugs regimen and local treatments for bilateral group D eyes or on the only eye.


Eligibility criteria: Inclusion Criteria:

Study 1 inclusion criteria:

* Patients affected by unilateral retinoblastoma groups A, B (according to the age), group C (according to the age and vitreous seeding),or bilateral retinoblastoma groups A, B, C (excluding the eyes with macular threat and bilateral group D eyes or on the only remaining eye) amenable to a conservative treatment (at least on one eye in bilateral disease) but needing initial chemotherapy because of the location, the size of the lesion (more than 4 mm of diameter), a vision threat or risks of intravitreal relapse making those patients not amenable to chemothermotherapy first line.
* Patients less than six months of age with unilateral retinoblastoma groups B, C, D, or bilateral very asymmetric with one eye group D and the other amenable to local treatments without chemotherapy.
* Children from 0 to 6 years old.

Study 2 inclusion criteria:

* Patients affected by unilateral or bilateral retinoblastoma group B (according to the age), group C (according to the age and vitreous seeding), or group D.
* Patients affected by bilateral retinoblastoma very asymmetric with a group D eye that can be treated by intraarterial chemotherapy by Melphalan and the other amenable to local treatments without chemotherapy.
* Children from 6 months to 6 years old.

Study 3 inclusion criteria:

* Children affected of bilateral group D retinoblastoma or on the only eye amenable to conservative treatment.
* Children from 0 to 6 years old.

Common inclusion criteria:

* Patients not previously treated by chemotherapy or radiotherapy for this tumour or another cancer.
* No contra-indications to the study treatments
* Possible long term follow-up.
* Written informed consent of the parents or the legal representative.
* Patients having social security cover.

Exclusion Criteria:

Study 1 exclusion criteria:

* Patients for whom a local treatment is possible without initial chemotherapy (tumour smaller than 4 mm and located far from optic nerve head or macula).
* Patients with an unilateral group D with massive tumour or group E eyes needing enucleation first line or after initial chemotherapy (in case of buphthalmia or suspected optic nerve invasion or extrascleral extension).
* Patients affected by bilateral retinoblastoma very asymmetric with a group D eye that can be treated by intraarterial chemotherapy by Melphalan and the other amenable to local treatments without chemotherapy.
* Patients with bilateral retinoblastoma and bilateral group D eyes or on the only remaining eye or presenting a bilateral macular threat requiring conservative treatment by a 6 cycles, three drugs regimen.

Study 2 exclusion criteria:

* Patients with a unilateral group D (extensive) or B or C but covering the optic nerve head or group E eyes for which enucleation is warranted first line or after chemotherapy (in case of buphthalmia or suspected optic nerve invasion or extrascleral extension).
* Patients with unilateral group D eye with tumour volume of more than 50% of eye volume, for whom a massive choroidal invasion could be associated (on clinical or imaging criteria) and for which enucleation is warranted.

Study 3 exclusion criteria:

* Patients for whom a local treatment is possible without chemoreduction (tumour smaller than 4 mm, distant from macula and from optic nerve head).
* Patients affected by bilateral retinoblastoma very asymmetric with a group D eye that can be treated by intraarterial chemotherapy by Melphalan and the other amenable to local treatments without chemotherapy.
* Patients with bilateral retinoblastoma without macular threat or groups A, B, C than can be treated with chemoreduction by VP16 and Carboplatin then chemothermotherapy without laser at day 8.

Common exclusion criteria:

* Patients older than 6 years old.
* Patients with extraocular retinoblastoma.
* Patients with a disease being a contra-indication to chemotherapy.
* Patients anteriorly treated by chemotherapy.
* Patients anteriorly treated by external beam irradiation.
* Patients anteriorly treated for another cancer.
* Follow-up not possible due to geographic distance from the center or for social or psychological reasons.
* Parents not having accepted the therapeutic strategy after explanations by the investigator.
* Contra-indication to the use of one of the drugs used in the study.

Primary outcomes:
measure: Rate of enucleation and external beam irradiation
timeFrame: From first day of treatment to 18 months after the end of treatments
Secondary outcomes:
measure: Number of relapses diagnosticated by fundus examination under general anesthesia until the age of 4 years, and without general anesthesia for older patients
timeFrame: 5 years
measure: Prospective evaluation of the systemic, ocular and general sides effects (short term) of the intravenous chemotherapy, intraarterial chemotherapy, combined to the local treatments as well as the intravitreal injections of Melphalan
timeFrame: 5 years
measure: Prospective evaluation of the systemic, ocular and general sides effects (medium and long term) of the intravenous chemotherapy, intraarterial chemotherapy, combined to the local treatments as well as the intravitreal injections of Melphalan
timeFrame: 5 years
measure: Response to intravitreal chemotherapy by Melphalan
timeFrame: 18 months
measure: Radiation doses received during intraarterial procedures
timeFrame: 18 months
measure: Number of patients presenting a long term second tumour
timeFrame: until 20 years old
Other outcomes:
Locations:
city: Paris
country: France
facility: Institut Curie
Study officials:
affiliation: Institut Curie - Paris - France
name: Isabelle Aerts, MD
role: STUDY_DIRECTOR
affiliation: Amiens (FR), University College Hospital
name: Catherine Devoldere, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Angers (FR), University College Hospital
name: Isabelle Pellier, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Besançon (FR), Jean Minjoz Hospital
name: Véronique Laithier, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Bordeaux (FR), Pellegrin Regional Hospital
name: Celine De Bouyn-Icher, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brest (FR), University College Hospital
name: Liana-Stephania Carausau, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Caen (FR), University College Hospital
name: Damien BODET, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clermont-Ferrand (FR), University College Hospital
name: Justyna Kanold, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dijon (FR), Bocage University College Hospital
name: Claire Briandet, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Grenoble (FR), University College Hospital
name: Dominique Plantaz, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Lille (FR), Oscar Lambret Center
name: Hélène Sudour-Bonnange, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Limoges (FR), University College Hospital
name: Christophe Piguet, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lyon (FR), Leon Berard Center
name: Cécile Faure Conter, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Marseille (FR), La Timone Children Hospital
name: Carole Coze, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Montpellier (FR), Arnaud de Villeneuve Hospital
name: Nicolas Sirvent, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nancy (FR), University College Hospital
name: Ludovic Mansuy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nantes (FR), University College Hospital
name: Estelle Thebaud, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nice (FR), University College Hospital
name: Marilyne Dupuy-Poiree, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Poitiers (FR), University College Hospital
name: Frederic Millot, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Reims (FR), Regional University College Hospital
name: Claire Pluchart, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rennes (FR), University College Hospital
name: chloé Puiseux, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rouen (FR), University College Hospital
name: Pascale Schneider, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Saint-Etienne (FR), University College Hospital
name: Jean-Louis Stephan, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Strasbourg (FR), University College Hospital
name: Natacha Entz-Werle, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Toulouse (FR), Children Hospital
name: Anne-Isabelle Bertozzi-Salamon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tours (FR), University College Hospital
name: Pascale BLOUIN, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Paris (FR), Adolphe Rothschild Ophtalmologic Foundation
name: Michel Piotin, MD
role: PRINCIPAL_INVESTIGATOR
References: