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

Medulloblastoma Clinical Trial

— RSMA2010  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01857453
• Other study ID #: 2012-002803-16
• Status: Recruiting
• Phase: Phase 2
• Start date: April 10, 2013
• Est. completion date: December 2021

Study information

• Verified date: July 2018
• Source: Central Hospital, Nancy, France
• Contact: Luc TAILLANDIER
• Phone: +33 3 83 85 16 88
• Email: l.taillandier[@]chu-nancy.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 97
• Est. completion date: December 2021
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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 ßHCG 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

Related Conditions & MeSH terms

• Medulloblastoma

Intervention

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
• 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

Locations

Country	Name	City	State
France	Chu Amiens	Amiens
France	Chu Bordeaux	Bordeaux
France	CHU CAEN	Caen
France	Hopitaux Civils de Colmar	Colmar
France	Cenre Georges Francois Leclerc	Dijon
France	Chru de Lille	Lille
France	Centre Leon Berrard	Lyon
France	Hopital de La Timone	Marseille
France	Centre Val D'Aurelle	Montpellier
France	Chu Nancy	Nancy
France	Centre René Ganducheau	Nantes
France	Chu de Nice	Nice
France	Chu Nimes	Nimes
France	AP HP Groupe Hospitalier Pitié Salpétrière	Paris
France	Institut Curie	Paris
France	Institut du Cancer COURLANCY	Reims
France	Centre Eugene Marquis	Rennes
France	Centre Paul Strauss	Strasbourg
France	Chu de Toulouse	Toulouse
France	Institut Gustave Roussy	Villejuif

Sponsors (18)

Lead Sponsor

Collaborator

Central Hospital, Nancy, France

Center Eugene Marquis, Centre Francois Baclesse, Centre Georges Francois Leclerc, Centre Hospitalier Universitaire, Amiens, Centre Leon Berard, Centre Paul Strauss, Centre René Gauducheau, CHU de Nice, CHU de Reims, CRLCC Val d'Aurelle, Montpellier, Groupe Hospitalier Pitie-Salpetriere, Hôpital de la Timone, Hôpitaux Civils de Colmar, Institut Claudius Regaud, Institut Gustave Roussy, VILLEJUIF, University Hospital, Bordeaux, University Hospital, Lille

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	survival without disease at 1 year		one year