Clinical trial NCT04681417: Ocular Conservative Treatment for Retinoblastoma : Efficacy of the New Management Strategies and Visual Outcome
Official title: Ocular Conservative Treatment for Retinoblastoma: Efficacy of the New Management Strategies and Visual Outcome - RETINO 2018
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Retinoblastoma
Keywords: Pediatric
Ocular conservative treatment in retinoblastoma
Lead sponsor: Institut Curie
Sponsor class: OTHER
Collaborators: name: Fondation Rothschild Paris
First posted: 2020-12-23
Enrollment: 225
Sex: ALL
Minimum age (years): 6
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Study 1: Rate of eye preservation
timeFrame: 24 months after randomization
measure: Visual function
timeFrame: when patient is 6 years old and at least 24 months of follow-up after study inclusion
Secondary outcomes:
measure: Ocular toxicity
timeFrame: Up to 24 months after inclusion in the study
measure: Systemic toxicity
timeFrame: Up to 24 months after inclusion in the study
measure: Relapse
timeFrame: within 24 months after inclusion
measure: Second malignant tumor
timeFrame: 24 months after study inclusion
measure: Additional assessment of visual function
timeFrame: In the year patients turn 6 years of age and at least 24 months of treatment
measure: Retinal assessment
timeFrame: In the year patients turn 6 years of age and at least 24 months of treatment
measure: Integration at school
timeFrame: In the year patients turn 6 years of age and at least 24 months of treatment
Other outcomes:
Locations:
city: Saint-Denis
country: France
facility: La Reunion - Chr Felix Guyon
state: La Réunion
city: Amiens
country: France
facility: Amiens Chu
city: Angers
country: France
facility: Angers Chu
city: Besancon
country: France
facility: BESANCON CHU Hopital Jean Minjoz
city: Bordeaux
country: France
facility: Bordeaux Chu
city: Brest
country: France
facility: BREST CHRU Hopital Morvan
city: Caen
country: France
facility: CAEN CHU
city: Clermont-Ferrand
country: France
facility: CHU ESTAING Centre Régional de Cancérologie et Therapie Cellulaire Pediatrique (CRCTCP)
city: Dijon
country: France
facility: DIJON CHU Hopital François Mitterand
city: Grenoble
country: France
facility: Grenoble Chu
city: Lille
country: France
facility: LILLE Centre Oscar Lambret
city: Limoges
country: France
facility: Limoges Chu
city: Lyon
country: France
facility: LYON Centre Léon Bérard
city: Marseille
country: France
facility: Marseille Chu
city: Montpellier
country: France
facility: MONTPELLIER CHU Hopital Arnaud De Villeneuve
city: Nantes
country: France
facility: NANTES CHU Hopital Mere-Enfant
city: Nice
country: France
facility: NICE CHU Hopital Archet 2
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: PARIS Fondation Ophtalmologique Adolphe de Rothschild
city: Poitiers
country: France
facility: Poitiers Chu
city: Reims
country: France
facility: Reims Chu
city: Rennes
country: France
facility: Rennes Chu
city: Rouen
country: France
facility: Rouen Chu
city: Saint Etienne
country: France
facility: Saint Etienne Chu
city: Strasbourg
country: France
facility: Strasbourg Chu
city: Toulouse
country: France
facility: Toulouse Chu
city: Tours
country: France
facility: TOURS CHU Hopital Clocheville
city: Vandoeuvre Les Nancy
country: France
facility: Nancy Chu
Study officials:
affiliation: Institut Curie
name: Livia LUMBROSO LE ROUIC, MD
role: PRINCIPAL_INVESTIGATOR
References: