Ocular Conservative Treatment for Retinoblastoma : Efficacy of the New Management Strategies and Visual Outcome

NCT ID: NCT04681417

Last Updated: 2025-11-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

225 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-25

Study Completion Date

2036-01-20

Brief Summary

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This protocol includes 2 independent studies. Both studies are multicenter studies, evaluating different therapeutic approaches in two different populations of patients:

* Study 1, a randomized phase-II study evaluating the efficacy of Intra-Arterial Chemotherapy (IAC) with melphalan and topotecan versus melphalan alone, both in association with ophthalmologic treatments.
* Study 2, a minimally invasive interventional study evaluating the results on visual function following reference treatment with intravenous (IV) chemotherapy in association with ophthalmologic or local ophthalmological treatment without IV chemotherapy.

Detailed Description

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Primary objective of the studies:

* Study 1: To evaluate the efficacy of IAC in term of local control of the disease in patients eligible for IAC (randomized phase II study);
* Study 2: To assess the visual function, based on World Health Organization (WHO) criteria, in patients eligible for other conservative treatments (IV chemotherapy in association with local ophthalmologic trématent or local ophthalmological treatment without IV chemotherapy; this is a minimally invasive interventional study).

Conditions

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Retinoblastoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Study 1: Melphalan or Melphalan + Topotecan

Randomized phase-II study evaluating the efficacy of Intra-Arterial Chemotherapy (IAC) with melphalan and topotecan versus melphalan alone, both in association with ophthalmologic treatments.

Group Type EXPERIMENTAL

Melphalan or Melphalan + Topotecan

Intervention Type DRUG

IAC: 2-6 cycles every 1 month (number based on the local tumor evolution), performed using radio-guided catheterization and delivery at the ostium of the ophthalmic artery, in neuroradiology operating room, and under General Anesthesia (GA). IAC will be administered at the Fondation Rothschild Hospital in collaboration with the Interventional Neuroradiology team.

Thermotherapy (local treatment)

Intervention Type DEVICE

Thermotherapy after carboplatin administered on Day 1

Cryotherapy (local treatment)

Intervention Type DEVICE

Cryotherapy (local treatment)

Iodine-125 plaques (local treatment)

Intervention Type DEVICE

Iodine-125 plaques (local treatment)

Intravitreal Melphalan chemotherapy injections (local treatment)

Intervention Type DRUG

Intravitreal Melphalan chemotherapy injections (local treatment)

Study 2: Etoposide, carboplatin and vincristine

Neoadjuvant chemotherapy involves 2 to 6 cycles of combined etoposide, carboplatin and vincristine in association with ophthalmologic treatments.

Group Type OTHER

etoposide, carboplatin and vincristine or local ophthalmological treatment without IV chemotherapy

Intervention Type DRUG

2 to 6 cycles of combined etoposide, carboplatin and vincristine or local ophthalmological treatment without IV chemotherapy : thermotherapy and/or cryotherapy and/or iodine-125 plaques and/or intravitreal chemotherapy injections

Carboplatin administered on Day 1

Intervention Type DRUG

Chemothermotherapy : Intravenous injection by carboplatin

Thermotherapy (local treatment)

Intervention Type DEVICE

Thermotherapy after carboplatin administered on Day 1

Cryotherapy (local treatment)

Intervention Type DEVICE

Cryotherapy (local treatment)

Iodine-125 plaques (local treatment)

Intervention Type DEVICE

Iodine-125 plaques (local treatment)

Intravitreal Melphalan chemotherapy injections (local treatment)

Intervention Type DRUG

Intravitreal Melphalan chemotherapy injections (local treatment)

Interventions

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Melphalan or Melphalan + Topotecan

IAC: 2-6 cycles every 1 month (number based on the local tumor evolution), performed using radio-guided catheterization and delivery at the ostium of the ophthalmic artery, in neuroradiology operating room, and under General Anesthesia (GA). IAC will be administered at the Fondation Rothschild Hospital in collaboration with the Interventional Neuroradiology team.

Intervention Type DRUG

etoposide, carboplatin and vincristine or local ophthalmological treatment without IV chemotherapy

2 to 6 cycles of combined etoposide, carboplatin and vincristine or local ophthalmological treatment without IV chemotherapy : thermotherapy and/or cryotherapy and/or iodine-125 plaques and/or intravitreal chemotherapy injections

Intervention Type DRUG

Carboplatin administered on Day 1

Chemothermotherapy : Intravenous injection by carboplatin

Intervention Type DRUG

Thermotherapy (local treatment)

Thermotherapy after carboplatin administered on Day 1

Intervention Type DEVICE

Cryotherapy (local treatment)

Cryotherapy (local treatment)

Intervention Type DEVICE

Iodine-125 plaques (local treatment)

Iodine-125 plaques (local treatment)

Intervention Type DEVICE

Intravitreal Melphalan chemotherapy injections (local treatment)

Intravitreal Melphalan chemotherapy injections (local treatment)

Intervention Type DRUG

Other Intervention Names

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Alkeran, Topotecan Accord; Topotecan Hospira chemotherapy etoposide, carboplatin and vincristine chemotherapy platinum-based chemotherapy Thermotherapy after carboplatin administered on Day 1

Eligibility Criteria

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Inclusion Criteria

1. Newly diagnosed retinoblastoma (RB).
2. Retinoblastoma with at least one eye eligible for conservative management.
3. Patients likely to be compliant with the study requirements and visits, including late follow-up.
4. Patients not previously treated with chemotherapy or radiotherapy for this or any other cancer.
5. Patients with no contraindication to the proposed treatments.
6. Informed consent signed by parents or legal representative.
7. French Social Security System coverage.


8.1. Children aged from 6 months to 6 years. 9. Retinoblastoma in at least one eye, deemed manageable with IAC in one side and without IV chemotherapy:

1. Unilateral Retinoblastoma classified as group B, C (if vitreous seeds \< 3 mm), D or E with no invasion of the anterior segment, and without massive tumor of more than 2/3 of the eye, eligible for conservative management, or
2. Bilateral Retinoblastoma but with very unbalanced lesions between the two eyes: one eye group D or E without invasion of the anterior segment or massive tumor of more than 2/3 of the eye, eligible for IAC, and the other eye eligible for local treatment only (without IAC).


8.2. Retinoblastoma eligible for conservative management although not manageable with IAC:

1. Unilateral Retinoblastoma in children below 6 months of age, classified as Group A, B, C or D, with or without vitreous seeding, compatible with conservative management, or
2. Bilateral Retinoblastoma classified as group A, B, C D, or E without invasion of the anterior segment, and/or massive tumors of more than 2/3 of the eye and eligible for conservative management.


1. RB not eligible for conservative management :

1. Extra-ocular extension of the disease, or
2. Group E eyes with invasion of the anterior segment, and/or massive tumors of more than 2/3 of the eye.
2. Patient older than 6 years of age.
3. Patients with another associated disease contra indicating systemic chemotherapy.
4. Previously treated retinoblastoma by chemotherapy.
5. Patients already treated for another malignant disease.
6. Patient with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
7. Patients whose parents have not accepted the treatment regimen after explanation of it.
8. Contraindication to study drug mentioned in SmPC (Summary of Products Characteristics) of the study drugs.
9. Inclusion in another experimental anti-cancer drug therapy.

10. Any contraindication or concomitant disease that would preclude the Study 1 treatment procedure and could delay treatment.

These patients should be eligible for Study 2.
Minimum Eligible Age

6 Months

Maximum Eligible Age

6 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fondation Rothschild Paris

OTHER

Sponsor Role collaborator

Institut Curie

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Livia LUMBROSO LE ROUIC, MD

Role: PRINCIPAL_INVESTIGATOR

Institut Curie

Locations

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La Reunion - Chr Felix Guyon

Saint-Denis, La Réunion, France

Site Status RECRUITING

Amiens Chu

Amiens, , France

Site Status RECRUITING

Angers Chu

Angers, , France

Site Status RECRUITING

BESANCON CHU Hopital Jean Minjoz

Besançon, , France

Site Status RECRUITING

Bordeaux Chu

Bordeaux, , France

Site Status RECRUITING

BREST CHRU Hopital Morvan

Brest, , France

Site Status RECRUITING

CAEN CHU

Caen, , France

Site Status RECRUITING

CHU ESTAING Centre Régional de Cancérologie et Therapie Cellulaire Pediatrique (CRCTCP)

Clermont-Ferrand, , France

Site Status RECRUITING

DIJON CHU Hopital François Mitterand

Dijon, , France

Site Status RECRUITING

Grenoble Chu

Grenoble, , France

Site Status RECRUITING

LILLE Centre Oscar Lambret

Lille, , France

Site Status RECRUITING

Limoges Chu

Limoges, , France

Site Status RECRUITING

LYON Centre Léon Bérard

Lyon, , France

Site Status RECRUITING

Marseille Chu

Marseille, , France

Site Status RECRUITING

MONTPELLIER CHU Hopital Arnaud De Villeneuve

Montpellier, , France

Site Status RECRUITING

NANTES CHU Hopital Mere-Enfant

Nantes, , France

Site Status RECRUITING

NICE CHU Hopital Archet 2

Nice, , France

Site Status RECRUITING

Institut Curie

Paris, , France

Site Status RECRUITING

PARIS Fondation Ophtalmologique Adolphe de Rothschild

Paris, , France

Site Status RECRUITING

Poitiers Chu

Poitiers, , France

Site Status RECRUITING

Reims Chu

Reims, , France

Site Status RECRUITING

Rennes Chu

Rennes, , France

Site Status RECRUITING

Rouen Chu

Rouen, , France

Site Status RECRUITING

Saint Etienne Chu

Saint-Etienne, , France

Site Status RECRUITING

Strasbourg Chu

Strasbourg, , France

Site Status RECRUITING

Toulouse Chu

Toulouse, , France

Site Status RECRUITING

TOURS CHU Hopital Clocheville

Tours, , France

Site Status RECRUITING

Nancy Chu

Vandœuvre-lès-Nancy, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Livia LUMBROSO LE ROUIC, MD

Role: CONTACT

+33(0)144324163

Christine FOULON, PhD

Role: CONTACT

+33(0)147111733

Facility Contacts

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Yves REGUERRE, MD

Role: primary

26(2)262905676

Camille KHANFARD, MD

Role: primary

+33(0)322087650

Isabelle PELLIER, MD

Role: primary

+33(0)241353863

Sébastien KLEIN, MD

Role: primary

+33(0)381219212

Céline DE BOUYN ICHER, MD

Role: primary

+33(0)557820434

Liana-Stéphania CARAUSU, MD

Role: primary

(+33) 02 98 22 37 70

Damien BODET, MD

Role: primary

+33(0)231064488

Justyna KANOLD, MD

Role: primary

(+33) 04 73 75 00 09

Claire BRIANDET, MD

Role: primary

+33(0)380293601

Anne PAGNIER, MD

Role: primary

04 76 76 58 93

Hélène SUDOUR BONNANGE, MD

Role: primary

+33(0)320295959

Christophe PIGUET, MD

Role: primary

+33(0)555056801

BENOIT DUMONT, MD

Role: primary

Role: backup

+33 (0)4 69 16 65 74

Carole COZE, MD

Role: primary

+33(0)491386821

Nicolas SIRVENT, MD

Role: primary

+33(0)467336519

LECULEE THEBAUD Estelle, MD

Role: primary

+33(0)240083610

Gwenaëlle DUHIL DE BENAZE, MD

Role: primary

+33(0)492036064

Livia LUMBROSO LE ROUIC, MD

Role: primary

+33(0)144324163

Isabelle AERTS, MD

Role: backup

+33(0)144324333

Raphaël BLANC, MD

Role: primary

+33(0)148036828

Frédéric MILLOT, MD

Role: primary

+33(0)549443078

Claire PLUCHART, MD

Role: primary

+33(0)326787515

Chloé PUISEUX, MD

Role: primary

+33(0)299265917

Cécile DUMESNIL DE MARICOURT, MD

Role: primary

+33(0)232888191

Jean-Louis STEPHAN, MD

Role: primary

+33(0)478828608

Natacha ENTZ WERLE, MD

Role: primary

+33(0)388128396

Anne-Isabelle BERTOZZI-SALAMON, MD

Role: primary

+33(0)534558613

Pascale BLOUIN, MD

Role: primary

+33(0)247474751

Ludovic MANSUY, MD

Role: primary

+33(0)383154734

Other Identifiers

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IC 2019-05

Identifier Type: -

Identifier Source: org_study_id

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