Clinical trial NCT01507506: Phase III Study Comparing 2 Brain Conformational Radiotherapy in Combination With Chemotherapy in the Treatment of Glioblastoma
Official title: Phase III Randomized Study Comparing 2 Brain Conformational Radiotherapy in Combination With Chemotherapy in the Treatment of Glioblastoma : Standard 3D Conformational Radiotherapy Versus Intensity-modulated Radiotherapy With Simultaneous-integrated Boost Guided by Magnetic Resonance Spectroscopic Imaging
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Glioblastoma
Keywords: Glioblastoma
Radiotherapy
Intensity modulated radiation therapy (IMRT)
Magnetic resonance spectroscopic imaging (MRSI)
Lead sponsor: Institut Claudius Regaud
Sponsor class: OTHER
First posted: 2012-01-11
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Overall survival defined as the time from randomization to the date of death or date of last follow-up news (censured data)
timeFrame: 8 years
Secondary outcomes:
measure: Progression-free survival, defined as the time from randomization to the date of progression or death
timeFrame: 8 years
measure: Safety evaluated according to the classification of NCI CTCAE (Common Terminology Criteria for Adverse Events)V3.0
timeFrame: 8 years
Other outcomes:
Locations:
city: Albi
country: France
facility: Clinique Claude Bernard
city: Clermont-ferrand
country: France
facility: Centre Jean Perrin
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Lyon
country: France
facility: Hospices Civils de Lyon (Hôpital Lyon Sud/Hôpital P. Wertheimer)
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: AP HM - Hôpital La Timone
city: Montpellier
country: France
facility: Centre Val d'Aurelle
city: Saint-Priest-En-Jarez
country: France
facility: Institut de Cancerologie Lucien Neuwirth
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Strasbourg
country: France
facility: CHU de Strasbourg
city: Toulouse
country: France
facility: Institut Claudius REGAUD
city: Valence
country: France
facility: Centre Marie Curie
Study officials:
References:
citation: Laprie A, Ken S, Filleron T, Lubrano V, Vieillevigne L, Tensaouti F, Catalaa I, Boetto S, Khalifa J, Attal J, Peyraga G, Gomez-Roca C, Uro-Coste E, Noel G, Truc G, Sunyach MP, Magne N, Charissoux M, Supiot S, Bernier V, Mounier M, Poublanc M, Fabre A, Delord JP, Cohen-Jonathan Moyal E. Dose-painting multicenter phase III trial in newly diagnosed glioblastoma: the SPECTRO-GLIO trial comparing arm A standard radiochemotherapy to arm B radiochemotherapy with simultaneous integrated boost guided by MR spectroscopic imaging. BMC Cancer. 2019 Feb 21;19(1):167. doi: 10.1186/s12885-019-5317-x.
citation: Ken S, Deviers A, Filleron T, Catalaa I, Lotterie JA, Khalifa J, Lubrano V, Berry I, Peran P, Celsis P, Moyal EC, Laprie A. Voxel-based evidence of perfusion normalization in glioblastoma patients included in a phase I-II trial of radiotherapy/tipifarnib combination. J Neurooncol. 2015 Sep;124(3):465-73. doi: 10.1007/s11060-015-1860-8. Epub 2015 Jul 19.