Ocular Conservative Treatment for Retinoblastoma : Efficacy of the New Management Strategies and Visual Outcome (RETINO 2018)

November 21, 2025 updated by: Institut Curie

Ocular Conservative Treatment for Retinoblastoma: Efficacy of the New Management Strategies and Visual Outcome - RETINO 2018

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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).

Study Type

Interventional

Enrollment (Estimated)

225

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Amiens, France, 80054
        • Recruiting
        • Amiens Chu
        • Contact:
        • Principal Investigator:
          • Camille KHANFARD, MD
      • Angers, France, 49033
        • Recruiting
        • Angers Chu
        • Contact:
        • Principal Investigator:
          • Isabelle PELLIER, MD
      • Besançon, France, 25030
        • Recruiting
        • BESANCON CHU Hopital Jean Minjoz
        • Contact:
        • Principal Investigator:
          • Sébastien KLEIN, MD
      • Bordeaux, France, 33076
        • Recruiting
        • Bordeaux CHU
        • Contact:
        • Principal Investigator:
          • Céline DE BOUYN ICHER, MD
      • Brest, France, 29609
        • Recruiting
        • BREST CHRU Hopital Morvan
        • Contact:
        • Principal Investigator:
          • Liana-Stéphania CARAUSU, MD
      • Caen, France, 14033
        • Recruiting
        • Caen CHU
        • Contact:
        • Principal Investigator:
          • Damien BODET, MD
      • Clermont-Ferrand, France, 63003
        • Recruiting
        • CHU ESTAING Centre Régional de Cancérologie et Therapie Cellulaire Pediatrique (CRCTCP)
        • Contact:
        • Principal Investigator:
          • Justyna KANOLD, MD
      • Dijon, France, 21079
        • Recruiting
        • DIJON CHU Hopital François Mitterand
        • Contact:
        • Principal Investigator:
          • Claire BRIANDET, MD
      • Grenoble, France, 38045
        • Recruiting
        • Grenoble Chu
        • Principal Investigator:
          • Anne PAGNIER, MD
        • Contact:
      • Lille, France, 59037
        • Recruiting
        • LILLE Centre Oscar Lambret
        • Contact:
        • Principal Investigator:
          • Hélène SUDOUR BONNANGE, MD
      • Limoges, France, 87042
        • Recruiting
        • Limoges Chu
        • Contact:
        • Principal Investigator:
          • Christophe Christophe PIGUET, MD
      • Lyon, France, 69373
        • Recruiting
        • LYON Centre Léon Bérard
        • Contact:
        • Contact:
          • Phone Number: +33 (0)4 69 16 65 74
        • Principal Investigator:
          • Benoit DUMONT, MD
      • Marseille, France, 13385
        • Recruiting
        • Marseille Chu
        • Contact:
        • Principal Investigator:
          • Carole COZE, MD
      • Montpellier, France, 34295
        • Recruiting
        • MONTPELLIER CHU Hopital Arnaud De Villeneuve
        • Contact:
        • Principal Investigator:
          • Nicolas SIRVENT, MD
      • Nantes, France, 44093
        • Recruiting
        • NANTES CHU Hopital Mere-Enfant
        • Contact:
        • Principal Investigator:
          • LECULEE THEBAUD Estelle, MD
      • Nice, France, 06202
        • Recruiting
        • NICE CHU Hopital Archet 2
        • Contact:
        • Principal Investigator:
          • Gwenaëlle DUHIL DE BENAZE, MD
      • Paris, France, 75005
        • Recruiting
        • Institut Curie
        • Contact:
        • Contact:
        • Principal Investigator:
          • LIvia LUMBROSO LE ROUIC, MD
      • Paris, France, 75019
        • Recruiting
        • PARIS Fondation Ophtalmologique Adolphe de Rothschild
        • Principal Investigator:
          • Raphaël Blanc, MD
        • Contact:
      • Poitiers, France, 86021
        • Recruiting
        • Poitiers CHU
        • Contact:
        • Principal Investigator:
          • Frédéric MILLOT, MD
      • Reims, France, 51092
        • Recruiting
        • Reims Chu
        • Contact:
        • Principal Investigator:
          • Claire PLUCHART, MD
      • Rennes, France, 35056
        • Recruiting
        • Rennes Chu
        • Contact:
        • Principal Investigator:
          • Chloé PUISEUX, MD
      • Rouen, France, 76000
        • Recruiting
        • Rouen Chu
        • Contact:
        • Principal Investigator:
          • Cécile DUMESNIL DE MARICOURT, MD
      • Saint-Etienne, France, 42055
        • Recruiting
        • Saint Etienne Chu
        • Contact:
        • Principal Investigator:
          • Jean-Louis STEPHAN, MD
      • Strasbourg, France, 67098
        • Recruiting
        • Strasbourg Chu
        • Contact:
        • Principal Investigator:
          • Natacha ENTZ WERLE, MD
      • Toulouse, France, 31026
        • Recruiting
        • Toulouse Chu
        • Contact:
        • Principal Investigator:
          • Anne-Isabelle BERTOZZI-SALAMON, MD
      • Tours, France, 37044
        • Recruiting
        • TOURS CHU Hopital Clocheville
        • Contact:
        • Principal Investigator:
          • Pascale BLOUIN, MD
      • Vandœuvre-lès-Nancy, France, 54500
        • Recruiting
        • Nancy Chu
        • Contact:
        • Principal Investigator:
          • Ludovic MANSUY, MD
    • La Réunion
      • Saint-Denis, La Réunion, France, 97405
        • Recruiting
        • La Reunion - Chr Felix Guyon
        • Contact:
        • Principal Investigator:
          • Yves REGUERRE, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 6 years (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Overall study 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.

Study 1 inclusion criteria:

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).

Study 2 inclusion criteria:

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.

Exclusion Criteria:

Overall study non-inclusion criteria:

  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.

    Study 1 non-inclusion criteria:

  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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: 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.
Other Names:
  • Alkeran, Topotecan Accord; Topotecan Hospira chemotherapy
Device: Thermotherapy (local treatment)
Thermotherapy after carboplatin administered on Day 1
Other Names:
  • Thermotherapy after carboplatin administered on Day 1
Device: Cryotherapy (local treatment)
Cryotherapy (local treatment)
Device: Iodine-125 plaques (local treatment)
Iodine-125 plaques (local treatment)
Drug: Intravitreal Melphalan chemotherapy injections (local treatment)
Intravitreal Melphalan chemotherapy injections (local treatment)
Other: Study 2: Etoposide, carboplatin and vincristine
Neoadjuvant chemotherapy involves 2 to 6 cycles of combined etoposide, carboplatin and vincristine in association with ophthalmologic treatments.
Device: Thermotherapy (local treatment)
Thermotherapy after carboplatin administered on Day 1
Other Names:
  • Thermotherapy after carboplatin administered on Day 1
Device: Cryotherapy (local treatment)
Cryotherapy (local treatment)
Device: Iodine-125 plaques (local treatment)
Iodine-125 plaques (local treatment)
Drug: Intravitreal Melphalan chemotherapy injections (local treatment)
Intravitreal Melphalan chemotherapy injections (local treatment)
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
Other Names:
  • etoposide, carboplatin and vincristine chemotherapy
Drug: Carboplatin administered on Day 1
Chemothermotherapy : Intravenous injection by carboplatin
Other Names:
  • platinum-based chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Study 1: Rate of eye preservation
Time Frame: 24 months after randomization
Rate of eye preservation in the 2 treatments' arms
24 months after randomization
Visual function
Time Frame: when patient is 6 years old and at least 24 months of follow-up after study inclusion
Percentage of patients with major, mild or no impairment of visual function according to WHO criteria, i.e. normal bilateral visual acuity (≥ 6/10) or mild bilateral visual impairment (3/10 to 5/10) according to tumor location and extension
when patient is 6 years old and at least 24 months of follow-up after study inclusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ocular toxicity
Time Frame: Up to 24 months after inclusion in the study
Percentage of patients with at least one grade-3 or -4 toxicity (CTCAE v. 5.0)
Up to 24 months after inclusion in the study
Systemic toxicity
Time Frame: Up to 24 months after inclusion in the study
Rate of specific grade 3-4 toxicity (CTCAE v. 5.0)
Up to 24 months after inclusion in the study
Relapse
Time Frame: within 24 months after inclusion
Percentage of patients with relapse within 24 months after inclusion, broken down into: Local relapse, Extra-ocular relapse
within 24 months after inclusion
Second malignant tumor
Time Frame: 24 months after study inclusion
Percentage of patients with second malignant tumor within 24 months after study inclusion
24 months after study inclusion
Additional assessment of visual function
Time Frame: In the year patients turn 6 years of age and at least 24 months of treatment
Additional assessment of visual function at follow-up: Percentage of patients at each of the four levels of visual acuity according to WHO criteria
In the year patients turn 6 years of age and at least 24 months of treatment
Retinal assessment
Time Frame: In the year patients turn 6 years of age and at least 24 months of treatment
Optical Coherence Tomography (OCT) and Optical Coherence Tomography-Angiography (OCT-A) measures on retina
In the year patients turn 6 years of age and at least 24 months of treatment
Integration at school
Time Frame: In the year patients turn 6 years of age and at least 24 months of treatment
Rate of children able to attend the common primary school : without specific help or with the help of a dedicated person and/or with specific features to facilitate reading and writing
In the year patients turn 6 years of age and at least 24 months of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut Curie

Collaborators

Fondation Rothschild Paris

Investigators

  • Principal Investigator: Livia LUMBROSO LE ROUIC, MD, Institut Curie

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 25, 2021

Primary Completion (Estimated)

January 20, 2035

Study Completion (Estimated)

January 20, 2036

Study Registration Dates

First Submitted

December 17, 2020

First Submitted That Met QC Criteria

December 22, 2020

First Posted (Actual)

December 23, 2020

Study Record Updates

Last Update Posted (Actual)

November 28, 2025

Last Update Submitted That Met QC Criteria

November 21, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IC 2019-05

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Sponsor will share de-identified data sets Documents generated under the project will be disseminated in accordance with Institut Curie policies.

IPD Sharing Time Frame

Data requests can be submitted starting 9 months after last article publication and will be made accessible for up to 12 months.

IPD Sharing 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).

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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