Clinical trial NCT01857453: Interest of a Dose Decrease for Radiotherapy Associated With Chemotherapy for Treatment of Standard Risk Adult Medulloblastomas
Official title: National, Multicentric, Prospective Phase II Study Estimating the Interest of a Dose Decrease for Radiation Therapy Associated With a Carboplatine and Etoposide Based Chemotherapy for the Treatment of Standard Risk Adult Medulloblastomas
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Medulloblastoma
Keywords: Adult Patients Medulloblatoma Standard risk group Chemotherapy Radiotherapy Quality of Life
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
Collaborators: name: University Hospital, Bordeaux
name: Centre Paul Strauss
name: Centre Hospitalier Universitaire de Nice
name: CRLCC Val d'Aurelle, Montpellier
name: Centre Georges Francois Leclerc
name: Gustave Roussy, Cancer Campus, Grand Paris
name: Centre Leon Berard
name: Groupe Hospitalier Pitie-Salpetriere
name: Hôpital de la Timone
name: CHU de Reims
name: Hopitaux Civils de Colmar
name: University Hospital, Lille
name: Institut Claudius Regaud
name: Centre Francois Baclesse
name: Center Eugene Marquis
name: Centre René Gauducheau
name: Centre Hospitalier Universitaire, Amiens
First posted: 2013-05-20
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: Inclusion Criteria:

* Pathologic diagnosis of medulloblastoma expect large cells type
* Patients between 18 and 70 years
* Résidual tumor les than 1.5 square centimeter (greater diameter)
* No sus tentorial or spinal location
* Absence of tumoral cells in the cerebrospinal fluid taken before, during or 14 days after surgery
* Absence of MYC amplification
* AID, B and C hepatitis positive serologies
* Negative βHCG dosage and effective contraception for potentially pregnant women
* Writed consent obtain

Exclusion Criteria:

* Age \< 18 or \> 70 years
* Previous diagnosis of medulloblastoma
* Previous treatment with chemotherapy
* Previous cranial or spinal radiation therapy
* Carboplatinum or etoposide contraindication
* Previous cancer in the five years before the inclusion except basocellular carcinoma of the skin and in situ cancer of the uterine cervix
* Severe renal renal insufficiency with a creatinine clearance \< 60 ml/min
* Liver insufficiency with a contraindication of carboplatinum or etoposide based chemotherapy or elevated transaminases \> 3N.
* Insufficient haematopoetic reserve (thrombocytes \< 100 000/mm3 ou neutrophil polynuclear \< 1500/mm3)
* Previous organ transplantation or immunosuppression
* Pregnant women or women without contraception
* Incapacity of respecting the recommanded follow up
* Participation in another therapeutic clinical trial
* Patient under custody
* Not social security regime membership

Primary outcomes:
measure: survival without disease at 1 year
timeFrame: one year
Secondary outcomes:
Other outcomes:
Locations:
city: Amiens
country: France
facility: Chu Amiens
city: Bordeaux
country: France
facility: Chu Bordeaux
city: Caen
country: France
facility: CHU CAEN
city: Colmar
country: France
facility: Hopitaux Civils de Colmar
city: Dijon
country: France
facility: Cenre Georges Francois Leclerc
city: Lille
country: France
facility: Chru de Lille
city: Lyon
country: France
facility: Centre Leon Berrard
city: Marseille
country: France
facility: Hopital de La Timone
city: Montpellier
country: France
facility: Centre Val D'Aurelle
city: Nancy
country: France
facility: Chu Nancy
city: Nantes
country: France
facility: Centre René Ganducheau
city: Nice
country: France
facility: Chu de Nice
city: Nimes
country: France
facility: Chu Nimes
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: AP HP Groupe Hospitalier Pitié Salpétrière
city: Reims
country: France
facility: Institut du Cancer COURLANCY
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Toulouse
country: France
facility: Chu de Toulouse
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: CHU NANCY - France
name: Luc TAILLANDIER
role: PRINCIPAL_INVESTIGATOR
References: