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

NCT04681417 | Recruiting Phase 2 DMC

• 1 other identifier: IC 2019-05
• Study Type: interventional
• Target: 225
• Locations: 1 country
• Sites: 28

Brief Summary

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.

Conditions

Retinoblastoma

Keywords

Pediatric; Ocular conservative treatment in retinoblastoma

Outcome Measures

Primary Outcomes (2)

• Study 1: Rate of eye preservation

  Rate of eye preservation in the 2 treatments' arms

  24 months after randomization

• Visual function

  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 Outcomes (7)

• Ocular toxicity

  Up to 24 months after inclusion in the study

• Systemic toxicity

  Up to 24 months after inclusion in the study

• Relapse

  within 24 months after inclusion

• Second malignant tumor

  24 months after study inclusion

• Additional assessment of visual function

  In the year patients turn 6 years of age and at least 24 months of treatment

Study Arms (2)

Study 1: Melphalan or Melphalan + Topotecan

EXPERIMENTAL

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; Device: Thermotherapy (local treatment); Device: Cryotherapy (local treatment); Device: Iodine-125 plaques (local treatment); Drug: Intravitreal Melphalan chemotherapy injections (local treatment)

Study 2: Etoposide, carboplatin and vincristine

OTHER

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

Drug: etoposide, carboplatin and vincristine or local ophthalmological treatment without IV chemotherapy; Drug: Carboplatin administered on Day 1; Device: Thermotherapy (local treatment); Device: Cryotherapy (local treatment); Device: Iodine-125 plaques (local treatment); Drug: Intravitreal Melphalan chemotherapy injections (local treatment)

Interventions

Melphalan or Melphalan + Topotecan 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.

Also known as: Alkeran, Topotecan Accord; Topotecan Hospira chemotherapy

Study 1: Melphalan or Melphalan + Topotecan

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

Also known as: etoposide, carboplatin and vincristine chemotherapy

Study 2: Etoposide, carboplatin and vincristine

Carboplatin administered on Day 1 DRUG

Chemothermotherapy : Intravenous injection by carboplatin

Also known as: platinum-based chemotherapy

Study 2: Etoposide, carboplatin and vincristine

Thermotherapy (local treatment) DEVICE

Thermotherapy after carboplatin administered on Day 1

Also known as: Thermotherapy after carboplatin administered on Day 1

Study 1: Melphalan or Melphalan + Topotecan; Study 2: Etoposide, carboplatin and vincristine

Cryotherapy (local treatment) DEVICE

Cryotherapy (local treatment)

Study 1: Melphalan or Melphalan + Topotecan; Study 2: Etoposide, carboplatin and vincristine

Iodine-125 plaques (local treatment) DEVICE

Iodine-125 plaques (local treatment)

Study 1: Melphalan or Melphalan + Topotecan; Study 2: Etoposide, carboplatin and vincristine

Intravitreal Melphalan chemotherapy injections (local treatment) DRUG

Intravitreal Melphalan chemotherapy injections (local treatment)

Study 1: Melphalan or Melphalan + Topotecan; Study 2: Etoposide, carboplatin and vincristine

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Institut Curie: lead
• Fondation Rothschild Paris: collaborator

Study Sites (28)

La Reunion - Chr Felix Guyon

Saint-Denis, La Réunion, 97405, France

RECRUITING

Amiens Chu

Amiens, 80054, France

RECRUITING

Angers Chu

Angers, 49033, France

RECRUITING

BESANCON CHU Hopital Jean Minjoz

Besançon, 25030, France

RECRUITING

Bordeaux Chu

Bordeaux, 33076, France

RECRUITING

BREST CHRU Hopital Morvan

Brest, 29609, France

RECRUITING

CAEN CHU

Caen, 14033, France

RECRUITING

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

Clermont-Ferrand, 63003, France

RECRUITING

DIJON CHU Hopital François Mitterand

Dijon, 21079, France

RECRUITING

Grenoble Chu

Grenoble, 38045, France

RECRUITING

LILLE Centre Oscar Lambret

Lille, 59037, France

RECRUITING

Limoges Chu

Limoges, 87042, France

RECRUITING

LYON Centre Léon Bérard

Lyon, 69373, France

RECRUITING

Marseille Chu

Marseille, 13385, France

RECRUITING

MONTPELLIER CHU Hopital Arnaud De Villeneuve

Montpellier, 34295, France

RECRUITING

NANTES CHU Hopital Mere-Enfant

Nantes, 44093, France

RECRUITING

NICE CHU Hopital Archet 2

Nice, 06202, France

RECRUITING

Institut Curie

Paris, 75005, France

RECRUITING

PARIS Fondation Ophtalmologique Adolphe de Rothschild

Paris, 75019, France

RECRUITING

Poitiers Chu

Poitiers, 86021, France

RECRUITING

Reims Chu

Reims, 51092, France

RECRUITING

Rennes Chu

Rennes, 35056, France

RECRUITING

Rouen Chu

Rouen, 76000, France

RECRUITING

Saint Etienne Chu

Saint-Etienne, 42055, France

RECRUITING

Strasbourg Chu

Strasbourg, 67098, France

RECRUITING

Toulouse Chu

Toulouse, 31026, France

RECRUITING

TOURS CHU Hopital Clocheville

Tours, 37044, France

RECRUITING

Nancy Chu

Vandœuvre-lès-Nancy, 54500, France

RECRUITING

MeSH Terms

Conditions

Retinoblastoma

Interventions

Melphalan; Topotecan; Etoposide; Carboplatin; Vincristine; Drug Therapy; Platinum Compounds; Hyperthermia, Induced; Cryotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Livia LUMBROSO LE ROUIC, MD

  Institut Curie

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Livia LUMBROSO LE ROUIC, MD

CONTACT

+33(0)144324163; livia.lumbroso-lerouic@curie.fr

Christine FOULON, PhD

CONTACT

+33(0)147111733; drci.promotion@curie.fr

Study Design

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

Study Record Dates

• First Submitted: December 17, 2020
• First Posted: December 23, 2020
• Study Start: March 25, 2021
• Primary Completion (Estimated): January 20, 2035
• Study Completion (Estimated): January 20, 2036
• Last Updated: November 28, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, 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 (28)