Phase III Study Comparing 2 Brain Conformational Radiotherapy in Combination With Chemotherapy in the Treatment of Glioblastoma

Phase 3

Terminated

• Conditions: Glioblastoma
• Interventions: Radiation: Radiotherapy; Radiation: Experimental arm

• Registration Number: NCT01507506
• Lead Sponsor: Institut Claudius Regaud

Brief Summary

This is a multi-institutional phase III clinical study of interventional type. The trial will include 220 patients with confirmed unifocal glioblastoma over a period of 3 years + 3 years of follow up.

Patients with unifocal glioblastoma (diagnosis confirmed by histology on tumoral biopsy or surgical specimen) and who meet all eligibility criteria will be randomized in one chemoradiotherapy arm :

* Conventional arm: 3-dimensional conformational radiotherapy + Temozolomide

* Experimental arm : simultaneous-integrated boost with intensity-modulated radiotherapy guided by magnetic resonance spectroscopic imaging + Temozolomide The patient monitoring will be regular and standardized. The main objective of this study is to improve overall survival of patients treated in experimental group (with simultaneous integrated boost).

Detailed Description

Not available

Study Timeline

• Study Start: 2011-03-15
• Study First Submitted: 2011-12-20
• Study First Submitted QC: 2012-01-10
• Study First Posted: 2012-01-11
• Primary Completion: 2020-01-02
• Study Completion: 2020-01-02
• Status Verified: 2021-01
• Last Update Submitted: 2021-01-11
• Last Update Posted: 2021-01-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 180

Inclusion Criteria

1. Patients must have unifocal glioblastoma (grade IV astrocytoma, WHO classification). The GBM can be:

   • Or resectable and the patient has received curative surgery
   • Or unresectable, and the largest tumor diameter (contrast enhancement) must be less than 5 cm on MRI

2. In all cases, the diagnosis must be confirmed by a pathologist. In patients for whom surgery is not possible, the diagnosis is confirmed by a biopsy of tumor tissue.

3. Methylation status of MGMT gene promoter is known

4. Patients who have undergone resection should have received an MRI or a scan after surgery in order to visualize residual tumor. If not, the operative report must be available.

5. Surgery or biopsy must have occurred 45 days before the start of radiotherapy.

6. WHO ≤ 2

7. Age ≥ 18 years

8. Signed Consent collected before any specific procedure in the study

9. Patient member in a national insurance scheme

Exclusion Criteria

1. Signs of hemorrhage on pre-radiotherapy MRI preventing a good spectrometric analysis

2. Patient with multifocal glioblastoma

3. Tumor located within 2 cm of the optic chiasm

4. Patient with leptomeningeal metastases,

5. patients prone to epileptic seizures despite treatment with anticonvulsant

6. Patients who received other previous treatment for glioblastoma multiforme

7. Abnormal haematological results at inclusion with:

   • Neutrophils < 1500/mm3
   • Blood-platelets < 100000/mm3

8. Severe or chronic renal insufficiency (creatinin clearance ≤ 30 ml/min calculated using Cockroft-Gault's formula

9. Patient unable to follow procedures, visits, examinations described in the study

10. Any usual formal indication against imaging examinations (important claustrophobia, pace maker ...)

11. Pregnant women or nursing mothers can not participate in the study. Women of childbearing age must have a negative pregnancy test within 72 hours prior to study entry

12. Men and women of childbearing age must use effective contraception at study entry and throughout the study

13. Any concomitant or previous malignant disease within 5 years prior to study entry

14. Any prior systemic chemotherapy within 5 years prior to inclusion (for malignant disease in medical history)

15. Any other medical conditions making the inclusion of the patient in the study inappropriate in the opinion of the investigator

16. Patient under legal guardianship

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Conventional arm	Radiotherapy	3-dimensional conformal radiotherapy + Temozolomide
Experimental arm	Experimental arm	simultaneous-integrated boost with intensity-modulated radiotherapy guided by magnetic resonance spectroscopic imaging + Temozolomide

Primary Outcome Measures

Name	Time	Method
Overall survival defined as the time from randomization to the date of death or date of last follow-up news (censured data)	8 years

Secondary Outcome Measures

Name	Time	Method
Safety evaluated according to the classification of NCI CTCAE (Common Terminology Criteria for Adverse Events)V3.0	8 years
Progression-free survival, defined as the time from randomization to the date of progression or death	8 years

Trial Locations

Locations (12)

Centre Paul Strauss; 🇫🇷 Strasbourg, France

Centre Leon Berard; 🇫🇷 Lyon, France

Clinique Claude Bernard; 🇫🇷 Albi, France

AP HM - Hôpital La Timone; 🇫🇷 Marseille, France

CHU de Strasbourg; 🇫🇷 Strasbourg, France

Centre Georges François Leclerc; 🇫🇷 Dijon, France

Institut Claudius REGAUD; 🇫🇷 Toulouse, France

Centre Marie Curie; 🇫🇷 Valence, France

Hospices Civils de Lyon (Hôpital Lyon Sud/Hôpital P. Wertheimer); 🇫🇷 Lyon, France

Centre Jean Perrin; 🇫🇷 Clermont-ferrand, France

Centre Val d'Aurelle; 🇫🇷 Montpellier, France

Institut de Cancerologie Lucien Neuwirth; 🇫🇷 Saint-Priest-En-Jarez, France