Adjuvant Treatment in Extensive Unilateral Retinoblastoma Primary Enucleated (RB SFCE 2009)

Retinoblastoma Clinical Trial

Official title:

Adjuvant Treatment in Extensive Unilateral Retinoblastoma Primary Enucleated

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02870907
• Other study ID #: IC 2009-04 RB SFCE 09
• Status: Recruiting
• Phase: Phase 2
• Start date: March 2010
• Est. completion date: September 2030

Study information

• Verified date: May 2024
• Source: Institut Curie
• Contact: Isabelle AERTS, MD
• Email: isabelle.aerts[@]curie.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Postoperative Treatment of Unilateral Retinoblastoma After Primary Enucleation according to histopathological risk factors of the International Retinoblastoma Staging Working Group.

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 .

• Intermediate risk group, 2 sub groups :

• Sub group 1 :

• Retrolaminar involvement without Invasion of surgical margin associated or not to massive choroidal involvement

• Anterior segment involvement.

• Intrascleral involvement.

• Sub Group 2 :

• Isolated massive choroidal involvement.

• High risk group :

• Invasion of the surgical margin of the optic nerve

• and/or microscopic extrascleral involvement

• Optic nerve meningeal sheat involvement .

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 185
• Est. completion date: September 2030
• Est. primary completion date: March 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Months to 10 Years

Eligibility

Inclusion Criteria:

1. Written informed consent - a signed informed consent and/or assent (as age appropriate) will be obtained according to institutional guidelines;

2. Male or female =2 months and <10 years of age at the time of signing the informed consent form;

3. Diagnosis of non familial extensive unilateral retinoblastoma treated by primary enucleation

4. 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).

5. Patients affiliated to a Social Security Regimen or beneficiary of the same

6. No chemotherapy or radiotherapy prior to administration of the first dose of study treatment for retinoblastoma or other tumor types

7. Without medical cons-indication to study drugs.

Exclusion Criteria:

• Bilateral and/or familial or trilateral retinoblastoma.

• 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

• Unilateral retinoblastoma with possibility of conservative treatment:

• Metastatic extension at diagnosis

• One inclusion criteria non observed

• Uncontrolled medical conditions, psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol

Related Conditions & MeSH terms

• Retinoblastoma

Intervention

Other:
• Observation
no post operative chemotherapy

Drug:
• Etoposide
100 mg/m²/d, IV (in the vein) from D1 to D5.
• Vincristine
1, 5 mg/m²/d, IV at D1.

Radiation:
• Orbital irradiation
45 Grays (Standard or external beam radiotherapy).

Drug:
• Carboplatin
160 mg/m²/d, IV from D1 to D5.
• Vincristine
1,5 mg/m²/d, IV at D22 and D26
• Cyclophosphamide
300 mg/m²/d, IV from D22 to D26.
• Carboplatin
560 mg/m²/d, IV at D1.
• Etoposide
100 mg/m²/d, IV from D1 to D5
• Carboplatin
160 mg/m²/d,IV from D1 to D5
• Thiotepa
15 mg, intrathecal Thiotepa injection at D1.
• Vincristine
1,5 mg/m²/d), IV at D22
• Cyclophosphamide
1000 mg/m²/d, IV from D22 à D24.

Procedure:
• Cytapheresis
Cytapheresis for peripheral blood stem cells collection after the primary or the secondary courses of Vincristine- Cyclophosphamid.

Drug:
• Carboplatin
AUC : 7/d, IV from D-8 to D-6.
• Etoposide
250 mg/m²/d, IV from D -5 to D-3.
• Thiotepa
300 mg/m²/d, IV from D-5 to D-3.

Procedure:
• Peripheral bood stem cell transplantation
at D0

Locations

Country	Name	City	State
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	CHU CAEN	Caen
France	Chu Estaing	Clermont Ferrand
France	Chu Bocage	Dijon
France	Chu de Grenoble	Grenoble
France	Centre Oscar Lambret	Lille
France	Chu Limoges	Limoges
France	Centre Leon Berard	Lyon
France	Hopital D'Enfants La Timone	Marseille
France	Hopital Arnaud de Villeneuve	Montpellier
France	Chu Nantes	Nantes
France	Chu de Nice	Nice
France	Institut Curie	Paris
France	Chu de Poitiers	Poitiers
France	Chur de Reims	Reims
France	Chu de Rennes	Rennes
France	Chu de Rouen	Rouen
France	Chu Saint Etienne	Saint Etienne
France	Chr Felix Guyon	Saint-Denis	La Réunion
France	Hoptial Hautepierre	Strasbourg
France	Chu Toulouse	Toulouse
France	Chu Tours	Tours
France	Chu Nancy	Vandoeuvre Les Nancy

Sponsors (1)

Lead Sponsor	Collaborator
Institut Curie

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of extra ocular relapses		5 years
Secondary	Evaluate long term and acute toxicities of adjuvant chemotherapy and orbital irradiation if necessary.	Number of participants with treatment-related Adverse Events as assessed by CTCAE v3.0.	5 years
Secondary	Number of patient with secondary bilateralisation		5 years
Secondary	Evaluate the different histopathological risk factors frequency	Number of patient in each histopathological risk group	5 years
Secondary	To determine tumors genomic	Tumor genomic characterization in order to provide some new prognosis factors and better understanding of tumorigenesis by using of NGS (Next Generation Sequencing) techniques	at the inclusion
Secondary	Evaluate sensitivity of MRI in detecting extra ocular extension	Number of extra ocular extension detected by MRI	At the inclusion