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

Retinoblastoma Clinical Trial

— RETINO2018  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04681417
• Other study ID #: IC 2019-05
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: March 25, 2021
• Est. completion date: January 20, 2036

Study information

• Verified date: November 2023
• Source: Institut Curie
• Contact: Livia LUMBROSO LE ROUIC, MD
• Phone: +33(0)144324163
• Email: livia.lumbroso-lerouic[@]curie.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 225
• Est. completion date: January 20, 2036
• Est. primary completion date: January 20, 2035
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 6 Years

Eligibility

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.

Related Conditions & MeSH terms

• Retinoblastoma

Intervention

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.
• 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
• Carboplatin administered on Day 1
Chemothermotherapy : Intravenous injection by carboplatin

Device:
• Thermotherapy (local treatment)
Thermotherapy after carboplatin administered on Day 1
• Cryotherapy (local treatment)
Cryotherapy (local treatment)
• Iodine-125 plaques (local treatment)
Iodine-125 plaques (local treatment)

Drug:
• Intravitreal Melphalan chemotherapy injections (local treatment)
Intravitreal Melphalan chemotherapy injections (local treatment)

Locations

Country	Name	City	State
France	Amiens Chu	Amiens
France	Angers Chu	Angers
France	BESANCON CHU Hopital Jean Minjoz	Besancon
France	Bordeaux Chu	Bordeaux
France	BREST CHRU Hopital Morvan	Brest
France	CAEN CHU	Caen
France	CHU ESTAING Centre Régional de Cancérologie et Therapie Cellulaire Pediatrique (CRCTCP)	Clermont-Ferrand
France	DIJON CHU Hopital François Mitterand	Dijon
France	Grenoble Chu	Grenoble
France	LILLE Centre Oscar Lambret	Lille
France	Limoges Chu	Limoges
France	LYON Centre Léon Bérard	Lyon
France	Marseille Chu	Marseille
France	MONTPELLIER CHU Hopital Arnaud De Villeneuve	Montpellier
France	NANTES CHU Hopital Mere-Enfant	Nantes
France	NICE CHU Hopital Archet 2	Nice
France	Institut Curie	Paris
France	PARIS Fondation Ophtalmologique Adolphe de Rothschild	Paris
France	Poitiers Chu	Poitiers
France	Reims Chu	Reims
France	Rennes Chu	Rennes
France	Rouen Chu	Rouen
France	Saint Etienne Chu	Saint Etienne
France	La Reunion - Chr Felix Guyon	Saint-Denis	La Réunion
France	Strasbourg Chu	Strasbourg
France	Toulouse Chu	Toulouse
France	TOURS CHU Hopital Clocheville	Tours
France	Nancy Chu	Vandoeuvre Les Nancy

Sponsors (2)

Lead Sponsor	Collaborator
Institut Curie	Fondation Rothschild Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Study 1: Rate of eye preservation	Rate of eye preservation in the 2 treatments' arms	24 months after randomization
Primary	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	Ocular toxicity	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
Secondary	Systemic toxicity	Rate of specific grade 3-4 toxicity (CTCAE v. 5.0)	Up to 24 months after inclusion in the study
Secondary	Relapse	Percentage of patients with relapse within 24 months after inclusion, broken down into: Local relapse, Extra-ocular relapse	within 24 months after inclusion
Secondary	Second malignant tumor	Percentage of patients with second malignant tumor within 24 months after study inclusion	24 months after study inclusion
Secondary	Additional assessment of visual function	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
Secondary	Retinal assessment	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
Secondary	Integration at school	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