Adjuvant Treatment in Extensive Unilateral Retinoblastoma Primary Enucleated (RB SFCE 2009)
- Registration Number
- NCT02870907
- Lead Sponsor
- Institut Curie
- Brief Summary
Postoperative Treatment of Unilateral Retinoblastoma After Primary Enucleation according to histopathological risk factors of the International Retinoblastoma Staging Working Group.
- Detailed Description
Post operative chemotherapy +/- radiotherapy according to histopathological risk factors of the International Retinoblastoma Staging Working Group.
* Low risk group :
* No optic nerve involvement.
* Intra and prelaminar involvement
* No choroidal involvement.
* Minimal superficial choroidal involvement .
...
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 185
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Written informed consent - a signed informed consent and/or assent (as age appropriate) will be obtained according to institutional guidelines;
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Male or female ≥2 months and <10 years of age at the time of signing the informed consent form;
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Diagnosis of non familial extensive unilateral retinoblastoma treated by primary enucleation
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In case of post operative chemotherapy, patients must have adequate organ function:
- Adequate hematopoietic function Neutrophils>1.0x109/l, Platelets >100 x 109/l.
- Adequate hepatic function: grade II NCI CTC
- Adequate renal function: serum creatinemia <1.5 x ULN for age with normal creatinine clearance estimated by SCHWARTZ formula
- Audiometry < Grade II de Brock.
- Echocardiography normal in case of high dose cyclophosphamide chemotherapy (3 g/m²).
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Patients affiliated to a Social Security Regimen or beneficiary of the same
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No chemotherapy or radiotherapy prior to administration of the first dose of study treatment for retinoblastoma or other tumor types
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Without medical cons-indication to study drugs.
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Bilateral and/or familial or trilateral retinoblastoma.
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Unilateral retinoblastoma with indication of primary chemotherapy before enucleation:
- One or several surgical risk factors
- Buphthalmia Exophthalmia.
- Peri ocular inflammatory signs.
- Extraocular extension :
- Radiological retrolaminar extension (more than 3 mm behind the lamina cribrosa) and or meningeal sheat optic nerve extension.
- Extrascleral extension
- Lymp nodes extension
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Unilateral retinoblastoma with possibility of conservative treatment:
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Metastatic extension at diagnosis
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One inclusion criteria non observed
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Uncontrolled medical conditions, psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description High risk group Orbital irradiation * Orbital irradiation * 3 cycles of two different types of alternating chemotherapy courses (id 6 courses) : * Etoposide (100 mg/m²/d) and Carboplatin (160 mg/m²/d) with intrathecal Thiotepa injection. * Vincristin (1,5 mg/m²/d) - Cyclophosphamide (1000 mg/m²/d) * Cytapheresis for peripheral blood stem cells collection after the primary or the secondary courses of Vincristine- Cyclophosphamide. * High dose chemotherapy : * Carboplatin (AUC : 7/d) - etoposide (250 mg/m²/d) - Thiotepa (300 mg/m²/d) * Peripheral bood stem cell transplantation. Low risk group Observation No treatment High risk group Cytapheresis * Orbital irradiation * 3 cycles of two different types of alternating chemotherapy courses (id 6 courses) : * Etoposide (100 mg/m²/d) and Carboplatin (160 mg/m²/d) with intrathecal Thiotepa injection. * Vincristin (1,5 mg/m²/d) - Cyclophosphamide (1000 mg/m²/d) * Cytapheresis for peripheral blood stem cells collection after the primary or the secondary courses of Vincristine- Cyclophosphamide. * High dose chemotherapy : * Carboplatin (AUC : 7/d) - etoposide (250 mg/m²/d) - Thiotepa (300 mg/m²/d) * Peripheral bood stem cell transplantation. High risk group Peripheral bood stem cell transplantation * Orbital irradiation * 3 cycles of two different types of alternating chemotherapy courses (id 6 courses) : * Etoposide (100 mg/m²/d) and Carboplatin (160 mg/m²/d) with intrathecal Thiotepa injection. * Vincristin (1,5 mg/m²/d) - Cyclophosphamide (1000 mg/m²/d) * Cytapheresis for peripheral blood stem cells collection after the primary or the secondary courses of Vincristine- Cyclophosphamide. * High dose chemotherapy : * Carboplatin (AUC : 7/d) - etoposide (250 mg/m²/d) - Thiotepa (300 mg/m²/d) * Peripheral bood stem cell transplantation. Intermediate risk sub group 1 Cyclophosphamide 2 cycles (4 courses): 2 courses of etoposide and Carboplatin from D1 to D5 and Vincristin at D22 and D26- Cyclophosphamide from D22 to D26. Intermediate risk sub group 1 Etoposide 2 cycles (4 courses): 2 courses of etoposide and Carboplatin from D1 to D5 and Vincristin at D22 and D26- Cyclophosphamide from D22 to D26. Intermediate risk sub group 2 Vincristine 2 courses of Vincristin and Carboplatin Intermediate risk sub group 1 Carboplatin 2 cycles (4 courses): 2 courses of etoposide and Carboplatin from D1 to D5 and Vincristin at D22 and D26- Cyclophosphamide from D22 to D26. Intermediate risk sub group 1 Vincristine 2 cycles (4 courses): 2 courses of etoposide and Carboplatin from D1 to D5 and Vincristin at D22 and D26- Cyclophosphamide from D22 to D26. Intermediate risk sub group 2 Carboplatin 2 courses of Vincristin and Carboplatin High risk group Carboplatin * Orbital irradiation * 3 cycles of two different types of alternating chemotherapy courses (id 6 courses) : * Etoposide (100 mg/m²/d) and Carboplatin (160 mg/m²/d) with intrathecal Thiotepa injection. * Vincristin (1,5 mg/m²/d) - Cyclophosphamide (1000 mg/m²/d) * Cytapheresis for peripheral blood stem cells collection after the primary or the secondary courses of Vincristine- Cyclophosphamide. * High dose chemotherapy : * Carboplatin (AUC : 7/d) - etoposide (250 mg/m²/d) - Thiotepa (300 mg/m²/d) * Peripheral bood stem cell transplantation. High risk group Etoposide * Orbital irradiation * 3 cycles of two different types of alternating chemotherapy courses (id 6 courses) : * Etoposide (100 mg/m²/d) and Carboplatin (160 mg/m²/d) with intrathecal Thiotepa injection. * Vincristin (1,5 mg/m²/d) - Cyclophosphamide (1000 mg/m²/d) * Cytapheresis for peripheral blood stem cells collection after the primary or the secondary courses of Vincristine- Cyclophosphamide. * High dose chemotherapy : * Carboplatin (AUC : 7/d) - etoposide (250 mg/m²/d) - Thiotepa (300 mg/m²/d) * Peripheral bood stem cell transplantation. High risk group Thiotepa * Orbital irradiation * 3 cycles of two different types of alternating chemotherapy courses (id 6 courses) : * Etoposide (100 mg/m²/d) and Carboplatin (160 mg/m²/d) with intrathecal Thiotepa injection. * Vincristin (1,5 mg/m²/d) - Cyclophosphamide (1000 mg/m²/d) * Cytapheresis for peripheral blood stem cells collection after the primary or the secondary courses of Vincristine- Cyclophosphamide. * High dose chemotherapy : * Carboplatin (AUC : 7/d) - etoposide (250 mg/m²/d) - Thiotepa (300 mg/m²/d) * Peripheral bood stem cell transplantation. High risk group Vincristine * Orbital irradiation * 3 cycles of two different types of alternating chemotherapy courses (id 6 courses) : * Etoposide (100 mg/m²/d) and Carboplatin (160 mg/m²/d) with intrathecal Thiotepa injection. * Vincristin (1,5 mg/m²/d) - Cyclophosphamide (1000 mg/m²/d) * Cytapheresis for peripheral blood stem cells collection after the primary or the secondary courses of Vincristine- Cyclophosphamide. * High dose chemotherapy : * Carboplatin (AUC : 7/d) - etoposide (250 mg/m²/d) - Thiotepa (300 mg/m²/d) * Peripheral bood stem cell transplantation. High risk group Cyclophosphamide * Orbital irradiation * 3 cycles of two different types of alternating chemotherapy courses (id 6 courses) : * Etoposide (100 mg/m²/d) and Carboplatin (160 mg/m²/d) with intrathecal Thiotepa injection. * Vincristin (1,5 mg/m²/d) - Cyclophosphamide (1000 mg/m²/d) * Cytapheresis for peripheral blood stem cells collection after the primary or the secondary courses of Vincristine- Cyclophosphamide. * High dose chemotherapy : * Carboplatin (AUC : 7/d) - etoposide (250 mg/m²/d) - Thiotepa (300 mg/m²/d) * Peripheral bood stem cell transplantation.
- Primary Outcome Measures
Name Time Method Rate of extra ocular relapses 5 years
- Secondary Outcome Measures
Name Time Method Evaluate long term and acute toxicities of adjuvant chemotherapy and orbital irradiation if necessary. 5 years Number of participants with treatment-related Adverse Events as assessed by CTCAE v3.0.
Number of patient with secondary bilateralisation 5 years Evaluate the different histopathological risk factors frequency 5 years Number of patient in each histopathological risk group
To determine tumors genomic at the inclusion Tumor genomic characterization in order to provide some new prognosis factors and better understanding of tumorigenesis by using of NGS (Next Generation Sequencing) techniques
Evaluate sensitivity of MRI in detecting extra ocular extension At the inclusion Number of extra ocular extension detected by MRI
Trial Locations
- Locations (27)
Chr Felix Guyon
🇫🇷Saint-Denis, La Réunion, France
Hopital Nord Chu Amiens
🇫🇷Amiens, France
Chu Angers
🇫🇷Angers, France
Hopital Jean Minioz
🇫🇷Besancon, France
Chu R; Pellegrin
🇫🇷Bordeaux, France
Chu Morvan
🇫🇷Brest, France
Centre Oscar Lambret
🇫🇷Lille, France
Institut Curie
🇫🇷Paris, France
Hopital D'Enfants La Timone
🇫🇷Marseille, France
Chur de Reims
🇫🇷Reims, France
Chu Toulouse
🇫🇷Toulouse, France
Chu Nancy
🇫🇷Vandoeuvre Les Nancy, France
CHU CAEN
🇫🇷Caen, France
Chu Estaing
🇫🇷Clermont Ferrand, France
Chu Bocage
🇫🇷Dijon, France
Chu de Grenoble
🇫🇷Grenoble, France
Centre Leon Berard
🇫🇷Lyon, France
Hopital Arnaud de Villeneuve
🇫🇷Montpellier, France
Chu Nantes
🇫🇷Nantes, France
Chu de Poitiers
🇫🇷Poitiers, France
Chu de Rouen
🇫🇷Rouen, France
Hoptial Hautepierre
🇫🇷Strasbourg, France
Chu Tours
🇫🇷Tours, France
Chu de Nice
🇫🇷Nice, France
Chu Limoges
🇫🇷Limoges, France
Chu de Rennes
🇫🇷Rennes, France
Chu Saint Etienne
🇫🇷Saint Etienne, France