Adjuvant Treatment in Extensive Unilateral Retinoblastoma Primary Enucleated (RB SFCE 2009) (RB SFCE 09)

Institut Curie

Status and phase: Active, not recruiting; Phase 2

Conditions: Retinoblastoma

Treatments: Radiation: Orbital irradiation; Drug: Carboplatin; Procedure: Peripheral bood stem cell transplantation; Procedure: Cytapheresis; Drug: Vincristine; Drug: Cyclophosphamide; Drug: Etoposide; Drug: Thiotepa; Other: Observation

Study type: Interventional

Funder types: Other

Identifiers

NCT02870907

IC 2009-04

Details and patient eligibility

About

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

Full 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 .

Enrollment: 195 estimated patients

Sex: All

Ages: 2 months to 10 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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195 participants in 4 patient groups

Low risk group

Experimental group

Description:

No treatment

Treatment:

Other: Observation

Intermediate risk sub group 1

Experimental group

Description:

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.

Treatment:

Drug: Carboplatin

Drug: Etoposide

Drug: Etoposide

Drug: Etoposide

Drug: Vincristine

Drug: Carboplatin

Drug: Cyclophosphamide

Drug: Vincristine

Drug: Cyclophosphamide

Drug: Carboplatin

Drug: Vincristine

Drug: Carboplatin

Intermediate risk sub group 2

Experimental group

Description:

2 courses of Vincristin and Carboplatin

Treatment:

Drug: Carboplatin

Drug: Vincristine

Drug: Carboplatin

Drug: Vincristine

Drug: Carboplatin

Drug: Vincristine

Drug: Carboplatin

High risk group

Experimental group

Description:

* 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.

Treatment:

Drug: Carboplatin

Drug: Etoposide

Drug: Etoposide

Drug: Etoposide

Drug: Vincristine

Drug: Carboplatin

Radiation: Orbital irradiation

Drug: Thiotepa

Drug: Cyclophosphamide

Drug: Vincristine

Drug: Thiotepa

Drug: Cyclophosphamide

Procedure: Cytapheresis

Drug: Carboplatin

Procedure: Peripheral bood stem cell transplantation

Drug: Vincristine

Drug: Carboplatin