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

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

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).

Study Overview

• Status: Terminated
• Conditions: Glioblastoma
• Intervention / Treatment: Radiation: Radiotherapy; Radiation: Experimental arm

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Albi, France, 81000
    • Clinique Claude Bernard
  • Clermont-ferrand, France, 63011
    • Centre Jean Perrin
  • Dijon, France, 21000
    • Centre Georges François Leclerc
  • Lyon, France, 69373
    • Centre LEON BERARD
  • Lyon, France, 69002
    • Hospices Civils de Lyon (Hôpital Lyon Sud/Hôpital P. Wertheimer)
  • Marseille, France, 13385
    • AP HM - Hôpital La Timone
  • Montpellier, France, 34298
    • Centre Val D'Aurelle
  • Saint-Priest-En-Jarez, France, 42271
    • Institut de Cancérologie Lucien Neuwirth
  • Strasbourg, France, 67065
    • Centre Paul Strauss
  • Strasbourg, France, 67065
    • CHU de Strasbourg
  • Toulouse, France, 31052
    • Institut Claudius Regaud
  • Valence, France, 26953
    • Centre Marie Curie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conventional arm; 3-dimensional conformal radiotherapy + Temozolomide	Radiation: Radiotherapy; Conventional arm: 3D conformational radiotherapy (arm A): 60 Gy per fractions of 2 Gy in 30 sessions on the PTV1 (contrast enhancement + 2 cm) with a linear accelerator equipped with a portal imaging. + Chemotherapy (Drug) :treatment should be combined with temozolomide during and after radiotherapy in a conventional treatment Stupp (Stupp et al. 2005), ie : during radiotherapy : Temozolomide 75 mg/m2/day by oral route every day,; post radiotherapy : 6 cycles of Temozolomide oral route : 150 mg/m2/day from D1 to D5 for the 1st cycle followed by 200 mg/m2/day from D28 to D32.
Experimental: Experimental arm; simultaneous-integrated boost with intensity-modulated radiotherapy guided by magnetic resonance spectroscopic imaging + Temozolomide	Radiation: Experimental arm; Conformational radiotherapy with simultaneous integrated boost by intensity modulation (Arm B): 60 Gy per fraction of 2 Gy in 30 sessions on the PTV1 (contrast enhancement + 2 cm) with concomitant daily superimposed boost on spectroscopic active region (PTV2) corresponding to the ratio Cho / NAA> 2 + 0.7 mm + contrast enhancement + 3mm. The PTV2 will receive a daily dose of 2.4 Gy for a cumulative dose of 72 Gy Only irradiation with simultaneous integrated boost are allowed + Chemotherapy (Drug) :treatment should be combined with temozolomide during and after radiotherapy in a conventional treatment Stupp (Stupp et al. 2005), ie : during radiotherapy : Temozolomide 75 mg/m2/day by oral route every day,; post radiotherapy : 6 cycles of Temozolomide oral route : 150 mg/m2/day from D1 to D5 for the 1st cycle followed by 200 mg/m2/day from D28 to D32.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

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

Collaborators and Investigators

• Sponsor: Institut Claudius Regaud

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2011
• Primary Completion (Actual): January 2, 2020
• Study Completion (Actual): January 2, 2020

Study Registration Dates

• First Submitted: December 20, 2011
• First Submitted That Met QC Criteria: January 10, 2012
• First Posted (Estimate): January 11, 2012

Study Record Updates

• Last Update Posted (Actual): January 12, 2021
• Last Update Submitted That Met QC Criteria: January 11, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Radiotherapy; Glioblastoma; Intensity modulated radiation therapy (IMRT); Magnetic resonance spectroscopic imaging (MRSI)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: 08 TETE 01