Conservative Treatments of Retinoblastoma

NCT02866136 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: IC 2011-05
• Study Type: interventional
• Target: 133
• Locations: 1 country
• Sites: 1

Brief Summary

Conservative treatments of retinoblastoma (RETINO 2011)

1. 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. 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. 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

Outcome Measures

Primary Outcomes (1)

• Rate of enucleation and external beam irradiation

  From first day of treatment to 18 months after the end of treatments

Secondary Outcomes (6)

• Number of relapses diagnosticated by fundus examination under general anesthesia until the age of 4 years, and without general anesthesia for older patients

  5 years

• 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

  5 years

• 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

  5 years

• Response to intravitreal chemotherapy by Melphalan

  18 months

• Radiation doses received during intraarterial procedures

  18 months

Study Arms (3)

(IV)Intravenous chemotherapy, laser diode

OTHER

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).

Drug: VP16, carboplatin; Drug: Carboplatin + laser day 1 (chemothermotherapy); Device: Laser (local treatment); Device: cryoapplication (local treatment); Radiation: I125 radioactive plaques (local treatment); Drug: intravitreal Melphalan (local treatment)

(IA) Intraarterial Melphalan

OTHER

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).

Drug: Melphalan; Device: Laser (local treatment); Device: cryoapplication (local treatment); Radiation: I125 radioactive plaques (local treatment); Drug: intravitreal Melphalan (local treatment)

(IV-PM) Intravenous 3 drugs chemotherapy

OTHER

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).

Drug: VP16, carboplatin, vincristin; Device: Laser (local treatment); Device: cryoapplication (local treatment); Radiation: I125 radioactive plaques (local treatment); Drug: intravitreal Melphalan (local treatment)

Interventions

VP16, carboplatin DRUG

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

Also known as: etoposide, vepesid, chemotherapy

(IV)Intravenous chemotherapy, laser diode

Melphalan DRUG

intraarterial injections, 3 to 6 cycles (1 month)

Also known as: Alkeran, chemotherapy

(IA) Intraarterial Melphalan

VP16, carboplatin, vincristin DRUG

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

Also known as: etoposide, vepesid, leurocristine, Oncovin, chemotherapy

(IV-PM) Intravenous 3 drugs chemotherapy

Carboplatin + laser day 1 (chemothermotherapy) DRUG

Chemothermotherapy : Intravenous injection by carboplatin and Laser at day 1

Also known as: Carbo-laser, platinum-based chemotherapy

(IV)Intravenous chemotherapy, laser diode

Laser (local treatment) DEVICE

Also known as: Laser diode

(IA) Intraarterial Melphalan; (IV)Intravenous chemotherapy, laser diode; (IV-PM) Intravenous 3 drugs chemotherapy

cryoapplication (local treatment) DEVICE

(IA) Intraarterial Melphalan; (IV)Intravenous chemotherapy, laser diode; (IV-PM) Intravenous 3 drugs chemotherapy

I125 radioactive plaques (local treatment) RADIATION

(IA) Intraarterial Melphalan; (IV)Intravenous chemotherapy, laser diode; (IV-PM) Intravenous 3 drugs chemotherapy

intravitreal Melphalan (local treatment) DRUG

(IA) Intraarterial Melphalan; (IV)Intravenous chemotherapy, laser diode; (IV-PM) Intravenous 3 drugs chemotherapy

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institut Curie: lead
• Fondation Rothschild Paris: collaborator

Study Sites (1)

Institut Curie

Paris, 75005, France

Location

MeSH Terms

Conditions

Retinoblastoma; Retinal Neoplasms

Interventions

Etoposide; Carboplatin; Drug Therapy; Melphalan; Vincristine; Platinum Compounds; Lasers; Lasers, Semiconductor

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Eye Neoplasms; Neoplasms by Site; Eye Diseases, Hereditary; Eye Diseases; Retinal Diseases

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Coordination Complexes; Therapeutics; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Inorganic Chemicals; Optical Devices; Equipment and Supplies; Radiation Equipment and Supplies

Study Officials

• Isabelle Aerts, MD

  Institut Curie - Paris - France

  STUDY DIRECTOR

• Catherine Devoldere, MD

  Amiens (FR), University College Hospital

  PRINCIPAL INVESTIGATOR

• Isabelle Pellier, MD

  Angers (FR), University College Hospital

  PRINCIPAL INVESTIGATOR

• Véronique Laithier, MD

  Besançon (FR), Jean Minjoz Hospital

  PRINCIPAL INVESTIGATOR

• Celine De Bouyn-Icher, MD

  Bordeaux (FR), Pellegrin Regional Hospital

  PRINCIPAL INVESTIGATOR

• Liana-Stephania Carausau, MD

  Brest (FR), University College Hospital

  PRINCIPAL INVESTIGATOR

• Damien BODET, MD

  Caen (FR), University College Hospital

  PRINCIPAL INVESTIGATOR

• Justyna Kanold, MD

  Clermont-Ferrand (FR), University College Hospital

  PRINCIPAL INVESTIGATOR

• Claire Briandet, MD

  Dijon (FR), Bocage University College Hospital

  PRINCIPAL INVESTIGATOR

• Dominique Plantaz, Prof.

  Grenoble (FR), University College Hospital

  PRINCIPAL INVESTIGATOR

• Hélène Sudour-Bonnange, MD

  Lille (FR), Oscar Lambret Center

  PRINCIPAL INVESTIGATOR

• Christophe Piguet, MD

  Limoges (FR), University College Hospital

  PRINCIPAL INVESTIGATOR

• Cécile Faure Conter, MD

  Lyon (FR), Leon Berard Center

  PRINCIPAL INVESTIGATOR

• Carole Coze, MD

  Marseille (FR), La Timone Children Hospital

  PRINCIPAL INVESTIGATOR

• Nicolas Sirvent, MD

  Montpellier (FR), Arnaud de Villeneuve Hospital

  PRINCIPAL INVESTIGATOR

• Ludovic Mansuy, MD

  Nancy (FR), University College Hospital

  PRINCIPAL INVESTIGATOR

• Estelle Thebaud, MD

  Nantes (FR), University College Hospital

  PRINCIPAL INVESTIGATOR

• Marilyne Dupuy-Poiree, MD

  Nice (FR), University College Hospital

  PRINCIPAL INVESTIGATOR

• Frederic Millot, MD

  Poitiers (FR), University College Hospital

  PRINCIPAL INVESTIGATOR

• Claire Pluchart, MD

  Reims (FR), Regional University College Hospital

  PRINCIPAL INVESTIGATOR

• chloé Puiseux, MD

  Rennes (FR), University College Hospital

  PRINCIPAL INVESTIGATOR

• Pascale Schneider, Prof.

  Rouen (FR), University College Hospital

  PRINCIPAL INVESTIGATOR

• Jean-Louis Stephan, Prof.

  Saint-Etienne (FR), University College Hospital

  PRINCIPAL INVESTIGATOR

• Natacha Entz-Werle, MD

  Strasbourg (FR), University College Hospital

  PRINCIPAL INVESTIGATOR

• Anne-Isabelle Bertozzi-Salamon, MD

  Toulouse (FR), Children Hospital

  PRINCIPAL INVESTIGATOR

• Pascale BLOUIN, MD

  Tours (FR), University College Hospital

  PRINCIPAL INVESTIGATOR

• Michel Piotin, MD

  Paris (FR), Adolphe Rothschild Ophtalmologic Foundation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2016
• First Posted: August 15, 2016
• Study Start: February 1, 2012
• Primary Completion: January 1, 2023
• Study Completion (Estimated): September 1, 2035
• Last Updated: November 24, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP
• Time Frame: Data requests can be submitted starting 9 months after last article publication and will be made accessible for up to 12 months.
• Access Criteria: Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).

Locations

FR (1)