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

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ClinicalTrials.gov Identifier: NCT02870907
Recruitment Status : Recruiting
First Posted : August 17, 2016
Last Update Posted : August 10, 2020
Sponsor:
Information provided by (Responsible Party):
Institut Curie

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

Condition or disease Intervention/treatment Phase
Retinoblastoma Other: Observation Drug: Etoposide Drug: Vincristine Radiation: Orbital irradiation Drug: Carboplatin Drug: Cyclophosphamide Drug: Thiotepa Procedure: Cytapheresis Procedure: Peripheral bood stem cell transplantation Phase 2

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 .

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 185 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Adjuvant Treatment in Extensive Unilateral Retinoblastoma Primary Enucleated
Study Start Date : March 2010
Estimated Primary Completion Date : March 2029
Estimated Study Completion Date : September 2029

Resource links provided by the National Library of Medicine


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: 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.

Experimental: Intermediate risk sub group 2
2 courses of Vincristin and Carboplatin
Drug: Vincristine
1, 5 mg/m²/d, IV at D1.

Drug: Carboplatin
560 mg/m²/d, IV at D1.

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

Drug: Etoposide
100 mg/m²/d, IV from D1 to D5

Drug: Carboplatin
160 mg/m²/d,IV from D1 to D5

Drug: Thiotepa
15 mg, intrathecal Thiotepa injection at D1.

Drug: Vincristine
1,5 mg/m²/d), IV at D22

Drug: 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.

Drug: Etoposide
250 mg/m²/d, IV from D -5 to D-3.

Drug: Thiotepa
300 mg/m²/d, IV from D-5 to D-3.

Procedure: Peripheral bood stem cell transplantation
at D0




Primary Outcome Measures :
  1. Rate of extra ocular relapses [ Time Frame: 5 years ]

Secondary Outcome Measures :
  1. 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.

  2. Number of patient with secondary bilateralisation [ Time Frame: 5 years ]
  3. Evaluate the different histopathological risk factors frequency [ Time Frame: 5 years ]
    Number of patient in each histopathological risk group

  4. 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

  5. Evaluate sensitivity of MRI in detecting extra ocular extension [ Time Frame: At the inclusion ]
    Number of extra ocular extension detected by MRI



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Ages Eligible for Study:   2 Months to 10 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02870907


Contacts
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Contact: Isabelle AERTS, MD isabelle.aerts@curie.fr

Locations
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Sponsors and Collaborators
Institut Curie
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Responsible Party: Institut Curie
ClinicalTrials.gov Identifier: NCT02870907    
Other Study ID Numbers: IC 2009-04 RB SFCE 09
First Posted: August 17, 2016    Key Record Dates
Last Update Posted: August 10, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Institut Curie:
primary enucleation
retinoblastoma
Additional relevant MeSH terms:
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Retinoblastoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Retinal Neoplasms
Eye Neoplasms
Neoplasms by Site
Eye Diseases, Hereditary
Eye Diseases
Retinal Diseases
Cyclophosphamide
Thiotepa
Carboplatin
Etoposide
Etoposide phosphate
Vincristine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic