Retinoblastoma MedDRA version: 20.0 Level: SOC Classification code 10010331 Term: Congenital, familial and genetic disorders System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Trade Name: ALKERAN Injectable
Pharmaceutical Form: Lyophilisate for solution for infusion
Trade Name: TOPOTECANE ACCORD 1mg/ml
Pharmaceutical Form: Solution for solution for infusion
Trade Name: T
Sponsors
Institut Curie
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria: Overall study inclusion criteria: 1.Newly diagnosed RB. 2.RB 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.RB in at least one eye, deemed manageable with IAC in one side and without IV chemotherapy: a.Unilateral RB classified as group B, C (if vitreous seeds =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Non-inclusion criteria: Overall study non-inclusion criteria: 1.RB not eligible for conservative management : a.Extra-ocular extension of the disease, or b.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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The 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 treatments; this is a minimally invasive interventional study). ;Secondary Objective: The Secondary objective(s): The secondary objectives in studies 1 and 2 are: •To assess treatment-related ocular and systemic toxicity (including ototoxicity for study 2); •To realize a full visual workup by visual acuity, visual field and orthoptic assessment; •To assess retinal impact with OCT (Optical Coherence Tomography) (standard B or C scans) and, whenever possible, using OCT-Angiography (OCT-A); •To assess the occurrence of local relapse, extra-ocular relapse, and second malignant tumor; •To assess the school integration modalities. The following secondary objective is specific of the Study 1: •To evaluate the incidence of neurological complications. The following secondary objective is specific of the Study 2: •To assess the rate of eye preservation over the study follow-up. ;Primary end point(s): Primary endpoint of the studies: Study 1: Rate of eye preservation in the investigational arm (Topotecan + Melphalan) and in the reference arm (Melphalan) 24 months after the date of randomization. Study 2: 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 the patient will have 6 years of age and at least 24 months of follow-up after study inclusion. ;Timepoint(s) of evaluation of this end point: Study 1: Rate of eye preservation in the investigational arm (Topotecan + Melphalan) and in th | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Study 1: endpoints evaluated within 24 months after randomization. Study 2: endpoints evaluated when the patient will have 6 years of age and at least 24 months of follow-up after study inclusion. Overall studies endpoints : -Percentage of patients with at least one grade-3 or -4 toxicity, and rate of specific grade 3-4 toxicity (CTCAE v. 5.0): -Ocular toxicity and systemic toxicity -During treatment and up to 24 months after inclusion in the study -Percentage of patients with relapse within 24 months after inclusion, broken down into: -Local relapse -Extra-ocular relapse -Percentage of patients with second malignant tumor within 24 months after study inclusion -Additional assessment of visual function at follow-up: -Percentage of patients at each of the four levels of visual acuity according to WHO criteria, i.e. mild/no impairment, moderate impairment, severe impairment and blindness; -Evaluation of peripheral visual field if possible -Retinal assessment by using OCT and OCT-A -Integration at school in the year patients turn 6 years of age: -Proportion of children able to attend the common primary school (without specific help, or with the help of a dedicated person and/or specific features to facilitate reading and writing) -Proportion of children attending specific schools or institutions for visually impaired children. Specific Study 1 endpoints -Level of angiography-related radiation dose received during the intra-arterial administration procedure; -Neurological status (complications); -Late check-up of Central Nervous System MRI. Specific Study 2 endpoints -Percentage of eye preservation at the 6 years-old functional evaluation. ;Timepoint(s) of evaluation of this end point: Study 1: endpoints evaluated within 24 months after randomization. Study 2: endpoints evaluated when the patient will have 6 years of age and at least 24 months of follow-up after study inclusion. | — |
Countries
France
Contacts
Public ContactCyrine EZZILI
Institut Curie
Outcome results
None listed