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

January 29, 2024 updated by: Institut Curie

Adjuvant Treatment in Extensive Unilateral Retinoblastoma Primary Enucleated

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 .

  • 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 .

Study Type

Interventional

Enrollment (Estimated)

185

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Amiens, France, 80054
        • Recruiting
        • Hopital Nord Chu Amiens
        • Principal Investigator:
          • Camille KHANFAR, MD
      • Angers, France, 49033
        • Recruiting
        • CHU Angers
        • Principal Investigator:
          • Isabelle PELLIER, MD
      • Besancon, France, 25030
        • Recruiting
        • Hopital Jean Minioz
        • Principal Investigator:
          • Veronique LAITHIER, MD
      • Bordeaux, France, 33076
        • Recruiting
        • Chu R; Pellegrin
        • Principal Investigator:
          • Céline BOUYN-ICHER, MD
      • Brest, France, 29609
        • Recruiting
        • CHU Morvan
        • Principal Investigator:
          • Liana-Sthéphania CARAUSU, MD
      • Caen, France, 14033
        • Recruiting
        • CHU Caen
        • Principal Investigator:
          • Damien BODET, MD
      • Clermont Ferrand, France, 63003
        • Recruiting
        • CHU Estaing
        • Principal Investigator:
          • Justyna KANOLD
      • Dijon, France, 21079
        • Recruiting
        • CHU Bocage
        • Principal Investigator:
          • Claire BRIANDET, MD
      • Grenoble, France, 38043
        • Recruiting
        • Chu de Grenoble
        • Principal Investigator:
          • Dominique PLANTAZ, MD
      • Lille, France, 59020
        • Recruiting
        • Centre Oscar Lambret
        • Principal Investigator:
          • Hélène SUDOUR-BONNANGE, MD
      • Limoges, France, 87042
        • Recruiting
        • Chu Limoges
        • Principal Investigator:
          • Christophe PIGUET, MD
      • Lyon, France, 69373
        • Recruiting
        • Centre Léon Bérard
        • Principal Investigator:
          • Benoît DUMONT, MD
      • Marseille, France, 13385
        • Recruiting
        • Hopital d'Enfants la Timone
        • Principal Investigator:
          • Carole COZE, MD
      • Montpellier, France, 34295
        • Recruiting
        • Hopital Arnaud de Villeneuve
        • Principal Investigator:
          • Nicolas SIRVENT, MD
      • Nantes, France, 44093
        • Recruiting
        • CHU Nantes
        • Principal Investigator:
          • Estelle THEBAUD, MD
      • Nice, France, 06202
        • Recruiting
        • CHU de Nice
        • Principal Investigator:
          • Maryline DUPUY-POIREE
      • Paris, France, 75005
        • Recruiting
        • Institut Curie
        • Principal Investigator:
          • Isabelle AERTS, MD
      • Poitiers, France, 86021
        • Recruiting
        • Chu de Poitiers
        • Principal Investigator:
          • Frédéric MILLOT, MD
      • Reims, France, 51100
        • Recruiting
        • Chur de Reims
        • Principal Investigator:
          • Claire PLUCHART, MD
      • Rennes, France, 35056
        • Recruiting
        • CHU de Rennes
        • Principal Investigator:
          • Chloé PUISEUX, MD
      • Rouen, France, 76031
        • Recruiting
        • CHU de Rouen
        • Principal Investigator:
          • Pascale SCHNEIDER, MD
      • Saint Etienne, France, 420555
        • Recruiting
        • CHU Saint Etienne
        • Principal Investigator:
          • Jean-Louis STEPHAN, MD
      • Strasbourg, France, 67098
        • Recruiting
        • Hoptial Hautepierre
        • Principal Investigator:
          • Natacha ENTZ WERLE, MD
      • Toulouse, France, 31026
        • Recruiting
        • CHU Toulouse
        • Principal Investigator:
          • Anne-Isabelle BERTOZZI-SALAMON, MD
      • Tours, France, 37044
        • Recruiting
        • Chu Tours
        • Principal Investigator:
          • Pascale BLOUIN, MD
      • Vandoeuvre Les Nancy, France, 54500
        • Recruiting
        • CHU Nancy
        • Principal Investigator:
          • Ludovic MANSUY, MD
    • La Réunion
      • Saint-Denis, La Réunion, France, 97405
        • Recruiting
        • Chr Felix Guyon
        • Principal Investigator:
          • Yves REGUERRE, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 months to 10 years (Child)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Low risk group
Other: Observation
no post operative chemotherapy
Experimental: Intermediate risk sub group 1
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.
Drug: Etoposide
100 mg/m²/d, IV (in the vein) from D1 to D5.
Drug: Vincristine
1, 5 mg/m²/d, IV at D1.
Drug: Carboplatin
160 mg/m²/d, IV from D1 to D5.
Drug: Vincristine
1,5 mg/m²/d, IV at D22 and D26
Drug: Cyclophosphamide
300 mg/m²/d, IV from D22 to D26.
Drug: Carboplatin
560 mg/m²/d, IV at D1.
Drug: Etoposide
100 mg/m²/d, IV from D1 to D5
Drug: Carboplatin
160 mg/m²/d,IV from D1 to D5
Drug: Vincristine
1,5 mg/m²/d), IV at D22
Drug: Cyclophosphamide
1000 mg/m²/d, IV from D22 à D24.
Drug: Carboplatin
AUC : 7/d, IV from D-8 to D-6.
Drug: Etoposide
250 mg/m²/d, IV from D -5 to D-3.
Experimental: Intermediate risk sub group 2
2 courses of Vincristin and Carboplatin
Drug: Vincristine
1, 5 mg/m²/d, IV at D1.
Drug: Carboplatin
160 mg/m²/d, IV from D1 to D5.
Drug: Vincristine
1,5 mg/m²/d, IV at D22 and D26
Drug: Carboplatin
560 mg/m²/d, IV at D1.
Drug: Carboplatin
160 mg/m²/d,IV from D1 to D5
Drug: Vincristine
1,5 mg/m²/d), IV at D22
Drug: Carboplatin
AUC : 7/d, IV from D-8 to D-6.
Experimental: High risk group
  • 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.
Drug: Etoposide
100 mg/m²/d, IV (in the vein) from D1 to D5.
Drug: Vincristine
1, 5 mg/m²/d, IV at D1.
Drug: Carboplatin
160 mg/m²/d, IV from D1 to D5.
Drug: Vincristine
1,5 mg/m²/d, IV at D22 and D26
Drug: Cyclophosphamide
300 mg/m²/d, IV from D22 to D26.
Drug: Carboplatin
560 mg/m²/d, IV at D1.
Drug: Etoposide
100 mg/m²/d, IV from D1 to D5
Drug: Carboplatin
160 mg/m²/d,IV from D1 to D5
Drug: Vincristine
1,5 mg/m²/d), IV at D22
Drug: Cyclophosphamide
1000 mg/m²/d, IV from D22 à D24.
Drug: Carboplatin
AUC : 7/d, IV from D-8 to D-6.
Drug: Etoposide
250 mg/m²/d, IV from D -5 to D-3.
Radiation: Orbital irradiation
45 Grays (Standard or external beam radiotherapy).
Drug: Thiotepa
15 mg, intrathecal Thiotepa injection at D1.
Procedure: Cytapheresis
Cytapheresis for peripheral blood stem cells collection after the primary or the secondary courses of Vincristine- Cyclophosphamid.
Drug: Thiotepa
300 mg/m²/d, IV from D-5 to D-3.
Procedure: Peripheral bood stem cell transplantation
at D0

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Rate of extra ocular relapses
Time Frame: 5 years
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate long term and acute toxicities of adjuvant chemotherapy and orbital irradiation if necessary.
Time Frame: 5 years
Number of participants with treatment-related Adverse Events as assessed by CTCAE v3.0.
5 years
Number of patient with secondary bilateralisation
Time Frame: 5 years
5 years
Evaluate the different histopathological risk factors frequency
Time Frame: 5 years
Number of patient in each histopathological risk group
5 years
To determine tumors genomic
Time Frame: 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
at the inclusion
Evaluate sensitivity of MRI in detecting extra ocular extension
Time Frame: At the inclusion
Number of extra ocular extension detected by MRI
At the inclusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut Curie

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2010

Primary Completion (Estimated)

March 1, 2030

Study Completion (Estimated)

September 1, 2030

Study Registration Dates

First Submitted

August 9, 2016

First Submitted That Met QC Criteria

August 12, 2016

First Posted (Estimated)

August 17, 2016

Study Record Updates

Last Update Posted (Actual)

January 31, 2024

Last Update Submitted That Met QC Criteria

January 29, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IC 2009-04 RB SFCE 09

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Sponsor will share de-identified data sets. Documents generated under the project will be disseminated in accordance with Institut Curie policies.

IPD Sharing Time Frame

Data requests can be submitted starting 9 months after last article publication and will be made accessible for up to 12 months.

IPD Sharing Access Criteria

Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).

IPD Sharing Supporting Information Type

  • SAP

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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