Conservative Treatments of Retinoblastoma

NCT ID: NCT02866136

Last Updated: 2025-11-24

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 133 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2035-09-30

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.

Conditions

Retinoblastoma; Children; Retinal Neoplasm

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

(IV)Intravenous chemotherapy, laser diode

Group 1 - Multicentric non randomised, phase II study for patients with retinoblastoma (unilateral group A,B according to age, group C according to the age and the vitreous seeding or bilateral groups A,B and C excluding the bilateral groups D or patients with bilateral macular threat).

Treatment by chemoreduction (VP16, carboplatin) followed by Carboplatin + laser day 1 (chemothermotherapy) without laser treatment at day 8 (decreasing laser sessions) combined to local treatments from third course (laser, cryoapplication, I125 radioactive plaques or intravitreal Melphalan).

Group Type: OTHER

VP16, carboplatin

Intervention Type: DRUG

Systemic treatment : Intravenous injections, 2 cycles (21 days)

Carboplatin + laser day 1 (chemothermotherapy)

Intervention Type: DRUG

Chemothermotherapy : Intravenous injection by carboplatin and Laser at day 1

Laser (local treatment)

Intervention Type: DEVICE

cryoapplication (local treatment)

Intervention Type: DEVICE

I125 radioactive plaques (local treatment)

Intervention Type: RADIATION

intravitreal Melphalan (local treatment)

Intervention Type: DRUG

(IA) Intraarterial Melphalan

Group 2 - Multicentric non randomised, phase II study for the patients with bilateral very asymmetric disease (group D retinoblastoma on one of the eye, and the other amenable to a local treatment without chemotherapy) or unilateral presentation group D and groups B/C according to the age and vitreous seeding.

Treatment by Melphalan chemotherapy administered by superselective catheterization of the ophthalmic artery and combined to local treatments (laser, cryoapplication, I125 radioactive plaques or intravitreal Melphalan).

Group Type: OTHER

Melphalan

Intervention Type: DRUG

intraarterial injections, 3 to 6 cycles (1 month)

Laser (local treatment)

Intervention Type: DEVICE

cryoapplication (local treatment)

Intervention Type: DEVICE

I125 radioactive plaques (local treatment)

Intervention Type: RADIATION

intravitreal Melphalan (local treatment)

Intervention Type: DRUG

(IV-PM) Intravenous 3 drugs chemotherapy

Group 3 - Multicentric non randomised, phase II study for the patients with bilateral group D retinoblastoma or with a group D retinoblastoma on the only remaining eye. Treatment by 6 cycles of three drugs (VP16, carboplatin, vincristin) regimen combined to local treatments from the third cycle (laser, cryoapplication, I125 radioactive plaques or intravitreal Melphalan).

Group Type: OTHER

VP16, carboplatin, vincristin

Intervention Type: DRUG

Systemic treatment : Intravenous injections, 6 cycles (21 days)

Laser (local treatment)

Intervention Type: DEVICE

cryoapplication (local treatment)

Intervention Type: DEVICE

I125 radioactive plaques (local treatment)

Intervention Type: RADIATION

intravitreal Melphalan (local treatment)

Intervention Type: DRUG

Interventions

VP16, carboplatin

Systemic treatment : Intravenous injections, 2 cycles (21 days)

Intervention Type: DRUG

Melphalan

intraarterial injections, 3 to 6 cycles (1 month)

Intervention Type: DRUG

VP16, carboplatin, vincristin

Systemic treatment : Intravenous injections, 6 cycles (21 days)

Intervention Type: DRUG

Carboplatin + laser day 1 (chemothermotherapy)

Chemothermotherapy : Intravenous injection by carboplatin and Laser at day 1

Intervention Type: DRUG

Laser (local treatment)

Intervention Type: DEVICE

cryoapplication (local treatment)

Intervention Type: DEVICE

I125 radioactive plaques (local treatment)

Intervention Type: RADIATION

intravitreal Melphalan (local treatment)

Intervention Type: DRUG

Other Intervention Names

etoposide, vepesid, chemotherapy; Alkeran, chemotherapy; etoposide, vepesid, leurocristine, Oncovin, chemotherapy; Carbo-laser, platinum-based chemotherapy; Laser diode

Eligibility Criteria

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.

• 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.

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

• 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

• 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.

• 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.

• 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.

• 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.

• Maximum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondation Rothschild Paris

OTHER

Sponsor Role: collaborator

Institut Curie

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Isabelle Aerts, MD

Role: STUDY_DIRECTOR

Institut Curie - Paris - France

Catherine Devoldere, MD

Role: PRINCIPAL_INVESTIGATOR

Amiens (FR), University College Hospital

Isabelle Pellier, MD

Role: PRINCIPAL_INVESTIGATOR

Angers (FR), University College Hospital

Véronique Laithier, MD

Role: PRINCIPAL_INVESTIGATOR

Besançon (FR), Jean Minjoz Hospital

Celine De Bouyn-Icher, MD

Role: PRINCIPAL_INVESTIGATOR

Bordeaux (FR), Pellegrin Regional Hospital

Liana-Stephania Carausau, MD

Role: PRINCIPAL_INVESTIGATOR

Brest (FR), University College Hospital

Damien BODET, MD

Role: PRINCIPAL_INVESTIGATOR

Caen (FR), University College Hospital

Justyna Kanold, MD

Role: PRINCIPAL_INVESTIGATOR

Clermont-Ferrand (FR), University College Hospital

Claire Briandet, MD

Role: PRINCIPAL_INVESTIGATOR

Dijon (FR), Bocage University College Hospital

Dominique Plantaz, Prof.

Role: PRINCIPAL_INVESTIGATOR

Grenoble (FR), University College Hospital

Hélène Sudour-Bonnange, MD

Role: PRINCIPAL_INVESTIGATOR

Lille (FR), Oscar Lambret Center

Christophe Piguet, MD

Role: PRINCIPAL_INVESTIGATOR

Limoges (FR), University College Hospital

Cécile Faure Conter, MD

Role: PRINCIPAL_INVESTIGATOR

Lyon (FR), Leon Berard Center

Carole Coze, MD

Role: PRINCIPAL_INVESTIGATOR

Marseille (FR), La Timone Children Hospital

Nicolas Sirvent, MD

Role: PRINCIPAL_INVESTIGATOR

Montpellier (FR), Arnaud de Villeneuve Hospital

Ludovic Mansuy, MD

Role: PRINCIPAL_INVESTIGATOR

Nancy (FR), University College Hospital

Estelle Thebaud, MD

Role: PRINCIPAL_INVESTIGATOR

Nantes (FR), University College Hospital

Marilyne Dupuy-Poiree, MD

Role: PRINCIPAL_INVESTIGATOR

Nice (FR), University College Hospital

Frederic Millot, MD

Role: PRINCIPAL_INVESTIGATOR

Poitiers (FR), University College Hospital

Claire Pluchart, MD

Role: PRINCIPAL_INVESTIGATOR

Reims (FR), Regional University College Hospital

chloé Puiseux, MD

Role: PRINCIPAL_INVESTIGATOR

Rennes (FR), University College Hospital

Pascale Schneider, Prof.

Role: PRINCIPAL_INVESTIGATOR

Rouen (FR), University College Hospital

Jean-Louis Stephan, Prof.

Role: PRINCIPAL_INVESTIGATOR

Saint-Etienne (FR), University College Hospital

Natacha Entz-Werle, MD

Role: PRINCIPAL_INVESTIGATOR

Strasbourg (FR), University College Hospital

Anne-Isabelle Bertozzi-Salamon, MD

Role: PRINCIPAL_INVESTIGATOR

Toulouse (FR), Children Hospital

Pascale BLOUIN, MD

Role: PRINCIPAL_INVESTIGATOR

Tours (FR), University College Hospital

Michel Piotin, MD

Role: PRINCIPAL_INVESTIGATOR

Paris (FR), Adolphe Rothschild Ophtalmologic Foundation

Locations

Institut Curie

Paris, , France

Countries

France

Other Identifiers

IC 2011-05

Identifier Type: -

Identifier Source: org_study_id