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

• ClinicalTrials.gov Identifier: NCT01507506
• Recruitment Status: Terminated
• First Posted: January 11, 2012
• Last Update Posted: January 12, 2021
• Sponsor: Institut Claudius Regaud
• Information provided by (Responsible Party): Institut Claudius Regaud

Tracking Information

• First Submitted Date: December 20, 2011
• First Posted Date: January 11, 2012
• Last Update Posted Date: January 12, 2021
• Actual Study Start Date: March 15, 2011
• Actual Primary Completion Date: January 2, 2020 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 10, 2012): Overall survival defined as the time from randomization to the date of death or date of last follow-up news (censured data) [ Time Frame: 8 years ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 10, 2012)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Glioblastoma

Intervention

• 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.
• 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.

Study Arms

• Active Comparator: Conventional arm
  3-dimensional conformal radiotherapy + Temozolomide
  Intervention: Radiation: Radiotherapy
• Experimental: Experimental arm
  simultaneous-integrated boost with intensity-modulated radiotherapy guided by magnetic resonance spectroscopic imaging + Temozolomide
  Intervention: Radiation: Experimental arm

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, Magné 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, Péran 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: June 28, 2018): 180
• Original Estimated Enrollment (submitted: January 10, 2012): 220
• Actual Study Completion Date: January 2, 2020
• Actual Primary Completion Date: January 2, 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT01507506
• Other Study ID Numbers: 08 TETE 01
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Institut Claudius Regaud
• Study Sponsor: Institut Claudius Regaud
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Institut Claudius Regaud
• Verification Date: January 2021