Chemotherapy for the treatment of standard risk adult medulloblastomas

Phase 2

Recruiting

Conditions: Adult medulloblastoma

Interventions: Drug: carboplatine
Drug: Etoposide
Radiation: radiation therapy

Registration Number: 2024-513243-85-00

Lead Sponsor: CHRU De Nancy

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: Ongoing, recruiting

Sex: All

Target Recruitment: 45

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
teatment arm	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
teatment arm	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
teatment arm	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

Primary Outcome Measures

Name	Time	Method
survival without disease at 1 year	one year

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (7): Centre Hospitalier Universitaire Amiens Picardie
🇫🇷
Amiens, France
Centre Leon Berard
🇫🇷
Lyon, France
Institut Regional Du Cancer De Montpellier
🇫🇷
Montpellier Cedex 5, France
Centre Hospitalier Universitaire De Lille
🇫🇷
Lille Cedex, France
Assistance Publique Hopitaux De Paris
🇫🇷
Paris Cedex 13, France
Centre Hospitalier Regional De Marseille
🇫🇷
Marseille, France
Institut Universitaire Du Cancer Toulouse-Oncopole
🇫🇷
Toulouse Cedex 9, France
Centre Hospitalier Universitaire Amiens Picardie
🇫🇷Amiens, France
Mathieu BOONE
Site contact
+33322668240
boone.mathieu@yahoo.fr