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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
225
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.
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
Chemothermotherapy : Intravenous injection by carboplatin
Thermotherapy after carboplatin administered on Day 1
Cryotherapy (local treatment)
Iodine-125 plaques (local treatment)
Intravitreal Melphalan chemotherapy injections (local treatment)
La Reunion - Chr Felix Guyon
Saint-Denis, La Réunion, France
RECRUITINGAmiens Chu
Amiens, France
RECRUITINGAngers Chu
Angers, France
RECRUITINGBESANCON CHU Hopital Jean Minjoz
Besançon, France
RECRUITINGBordeaux Chu
Bordeaux, France
RECRUITINGBREST CHRU Hopital Morvan
Brest, France
RECRUITINGCAEN CHU
Caen, France
RECRUITINGCHU ESTAING Centre Régional de Cancérologie et Therapie Cellulaire Pediatrique (CRCTCP)
Clermont-Ferrand, France
RECRUITINGDIJON CHU Hopital François Mitterand
Dijon, France
RECRUITINGGrenoble Chu
Grenoble, France
RECRUITING...and 18 more locations
Study 1: Rate of eye preservation
Rate of eye preservation in the 2 treatments' arms
Time frame: 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
Time frame: when patient is 6 years old and at least 24 months of follow-up after study inclusion
Ocular toxicity
Percentage of patients with at least one grade-3 or -4 toxicity (CTCAE v. 5.0)
Time frame: Up to 24 months after inclusion in the study
Systemic toxicity
Rate of specific grade 3-4 toxicity (CTCAE v. 5.0)
Time frame: Up to 24 months after inclusion in the study
Relapse
Percentage of patients with relapse within 24 months after inclusion, broken down into: Local relapse, Extra-ocular relapse
Time frame: within 24 months after inclusion
Second malignant tumor
Percentage of patients with second malignant tumor within 24 months after study inclusion
Time frame: 24 months after study inclusion
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
Time frame: In the year patients turn 6 years of age and at least 24 months of treatment
Retinal assessment
Optical Coherence Tomography (OCT) and Optical Coherence Tomography-Angiography (OCT-A) measures on retina
Time frame: In the year patients turn 6 years of age and at least 24 months of treatment
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
Time frame: In the year patients turn 6 years of age and at least 24 months of treatment
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