Interest of a Dose Decrease for Radiotherapy Associated With Chemotherapy for Treatment of Standard Risk Adult Medulloblastomas

Summary

Adult medulloblastoma is a rare tumour.

The "standard risk " group (complete surgery or residual tumour lower than 1,5 cm2, absence of malignant cells in the cerebrospinal fluid, absence of metastasis, absence of MYC amplification and exclusion of large cells medulloblastoma) concerns, for the adult population, a majority of patients at diagnosis (about ¾ of cases).

Conventional treatment is classically based on a 54/36 Gy cranio-spinal radiotherapy (54 Gy on the posterior fossa and 36 Gy on the nevraxis).

This treatment is associated with an acute toxicity (haematological, cutaneous, digestive and general) wich decreases gradually when patient goes away from the treatment period.

For this category of patients and this modality of treatment, The French intergroup experience, pleads in favour of a late and progressive neurotoxicity.

This neurotoxicity is associated with a clear degradation of the quality of life.

In the light of paediatric studies :

We propose a phase II study to estimate the interest of a decrease of radiation doses compensated by a chemotherapy according to the following schedule

1. carboplatine + etoposide based chemotherapy every 28 days x 2
2. followed by, less than 80 days after the surgery, radiation therapy with 24 Gy on the in toto neuro axis and 54 Gy on the post operative bed.

The majority of French centres concerned with the neuro-oncology are involved in this trial.

About 25 new cases by year are waited. A centralized analysis of pathological slides and of the pre and post surgery Magnetic Resonance Imaging is foreseen.

The main objective is to estimate the survival without disease at 1 year

Secondary objectives associate the evaluations of the rate of complete response at the end of procedure, the overall survival, the survival without disease, the survival without events, the neurocognitiv toxicity, the endocrine toxicity, the hearing toxicity and the time until definitive deterioration of the quality of life Associated studies

Two associated studies are besides foreseen (parallel search for co-financing):

1. A biologic study is planed with the aim to confirm, by morphological, genomic and transcriptomic studies, the interest, for the adult population, of the prognostic markers used in paediatric population
2. A radiological study is planed with the aim to estimate the interest :

* of a multimodal follow-up (spectroscopy and perfusion imaging) for the premature detection of recurrences
* of the study of functional connectivity in correlation with the neuropsychological follow-up for the analysis of the aetiology and premature markers of neurotoxicity.

Conditions

• Medulloblastoma

Interventions

DRUG

carboplatine

carboplatine + etoposide based chemotherapy followed by radiation therapy with 24 Gy on the in toto neuro axis and 54 Gy on the post operative bed

DRUG

Etoposide

carboplatine + etoposide based chemotherapy followed by radiation therapy with 24 Gy on the in toto neuro axis and 54 Gy on the post operative bed

RADIATION

radiation therapy

carboplatine + etoposide based chemotherapy followed by radiation therapy with 24 Gy on the in toto neuro axis and 54 Gy on the post operative bed

Sponsors & Collaborators

• University Hospital, Bordeaux

  collaborator OTHER

• Centre Paul Strauss

  collaborator OTHER

• Centre Hospitalier Universitaire de Nice

  collaborator OTHER

• CRLCC Val d'Aurelle, Montpellier

  collaborator UNKNOWN

• Centre Georges Francois Leclerc

  collaborator OTHER

• Gustave Roussy, Cancer Campus, Grand Paris

  collaborator OTHER

• Centre Leon Berard

  collaborator OTHER

• Groupe Hospitalier Pitie-Salpetriere

  collaborator OTHER

• Hôpital de la Timone

  collaborator OTHER

• CHU de Reims

  collaborator OTHER

• Hopitaux Civils de Colmar

  collaborator OTHER

• University Hospital, Lille

  collaborator OTHER

• Institut Claudius Regaud

  collaborator OTHER

• Centre Francois Baclesse

  collaborator OTHER

• Center Eugene Marquis

  collaborator OTHER

• Centre René Gauducheau

  collaborator OTHER

• Centre Hospitalier Universitaire, Amiens

  collaborator OTHER

• Central Hospital, Nancy, France

  lead OTHER

Principal Investigators

• Luc TAILLANDIER · CHU NANCY - France

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-04-10

Primary Completion

2018-12-31

Completion

2021-12-31

Countries

• France

Study Locations