Simultaneous Integrated Boost FDOPA Positron Emission Tomography (PET) Guided in Patients With Partially- or Non-operated Glioblastoma (SIB-DOPA)

Simultaneous Integrated Boost FDOPA PET Guided in Patients With Partially- or Non-operated Glioblastoma

Glioblastoma (GBM) is the most common primary brain cancer in adults. Surgery, chemoradiotherapy (temozolomide TMZ) and then adjuvant TMZ is the standard treatment. But, most patients relapse in a median time of 8-9 months; the median overall survival (OS) ranged from 15 to 18 months.

Some frail patients received hypofractionated radiation and concomitant and adjuvant TMZ. For some, the radiation dose is not optimal. Moreover, recurrences develop mainly in the initial tumor site. These two reasons justify increasing the dose. To limit the movements of these fragile patients, the method consists of increasing the dose without increasing the number of sessions by using the Simultaneous Integrated Boost (SIB) which increases the dose in targeted volumes while the rest of the volume receives a minimum dose. A phase I trial showed the possibility of increasing the dose in SIB up to 80 Gy in a part of the GBM enhanced on MRI.

FDOPA PET detects certain more aggressive tumor areas, areas likely to recur. Integrating them into the SIB seems appropriate. A phase II trial showed the interest of SIB guided by FDOPA PET in terms of progression-free survival but without impact on OS. This study differed from the one the investigators propose, because a dose and conventional fractionation, identical to that of the European Organization for Research and Treatment of Cancer/National Cancer Information Center (NCIC/EORTC) protocol were delivered, the gliomas were unmethylated MGMT, less likely to respond. Studies with SIB and hypofractionation are often retrospective and for others, hypofractionation was debatable and the dose increase was not based on PET capture but on MRI. However, a prospective phase II study, with SIB and hypofractionation, not integrating FDopa PET has demonstrated the relevance of SIB.

In this project, the investigators propose to use the integrated boost technique (SIB) guided by PET FDOPA to increase the radiation dose in GBM, in patients either fragile and partially operated, or only biopsied and for whom the prognosis is the most pejorative.

Study Overview

• Status: Not yet recruiting
• Conditions: Glioblastoma Multiforme, Adult
• Intervention / Treatment: Procedure: Integrated boost technique (SIB) guided by PET FDOPA

• Study Type: Interventional
• Enrollment (Anticipated): 75
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Manon VOEGELIN; Phone Number: +33(0)368339523; Email: m.voegelin@icans.eu
• Study Contact Backup: Name: claire vit; Phone Number: +33(0)368339523; Email: c.vit@icans.eu

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:

• Unfit patient without indication to the STUPP protocol :

Cohort 1 : Non-operable patients and ≥ 18 years old or ≤ 70 years old and Karnofsky Index (KI) ≥ 50% on inclusion AND Result of a biopsy available Cohort 2 : Patients > 70 years old and Balducci score I or II and KI ≥ 60% on inclusion AND Partial resection (defined on the remnographic criteria of postoperative MRI) OR biopsy result available

• Histologically proven glioblastoma
• Increased metabolism of amino acids in PET FDOPA allowing contouring the Biological Target Volume (BTV)

Exclusion Criteria:

• Patients with an indication for irradiation according to the STUPP protocol (fit patient)
• Patient with a contraindication to MRI or PET
• Limit of the provisional target volume or Planning target volume (PTV), second PTV < 2 cm from the chiasm and the optic nerves
• Absence of uptake of FDopa

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SIB-DOPA	Procedure: Integrated boost technique (SIB) guided by PET FDOPA; intensity-modulated irradiation scheme with integrated boost technique (SIB) guided by PET FDOPA during the chemo-radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Evaluate the overall survival (OS) of patients with glioblastoma treated with integrated boost (SIB) with increased dose guided by FDOPA PET	At 24 months after inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sites of progression: distant, marginal or in-field progression	The progression will be defined by its location by comparing the progression imaging with that used for dosimetry. It will be considered "distant" if it develops beyond the 95% isodose, "marginal" if it cuts the 95% isodose and "in-field" if it is completely within the 95% isodose. The 95% isodose is the reference isodose for the prescription of hypofractionated radiotherapy.	At the date of progression, assessed up to 24 months
Characterize the PET parameters during progression	PET Parameters: Standardized Uptake Value (SUV) max tumor, SUV max tumor/healthy tissue, SUV max T/striatum; SUV mean tumor, SUV mean tumor/healthy tissue, SUV mean T/striatum	At the date of progression, assessed up to 24 months
Evolution of the PET parameters	PET Parameters: Standardized Uptake Value (SUV) max tumor, SUV max tumor/healthy tissue, SUV max T/striatum; SUV mean tumor, SUV mean tumor/healthy tissue, SUV mean T/striatum	Change between baseline and the date of progression, assessed up to 24 months
Correlate O6-Methylguanine-DNA Methyltransferase (MGMT) promoter methylation status and Progression-Free Survival	MGMT promoter methylation status (binary variable, determined by either PCR or immunohistochemistry)	At 24 months after inclusion
Correlate O6-Methylguanine-DNA Methyltransferase (MGMT) promoter methylation status and acute toxicities	MGMT promoter methylation status (binary variable, determined by either PCR or immunohistochemistry)	At 24 months after inclusion
Progression-Free Survival (PFS)	To assess the progression-free survival (PFS) of patients with glioblastoma treated with SIB with increased dose guided by FDOPA PET	At 24 months after inclusion
Assess the rate of acute complications of grade ≥ 3	Acute toxicities are defined as toxicities by the Common Terminology Criteria for Adverse Events (CTCAE v5) occurring within 6 months of the start of radiotherapy.	At 6 months after the start of radiotherapy
Assess quality of life measured with Quality of Life Questionnaire-Cancer 30items (QLQ-C30)	The quality of life will be measured at the inclusion with Quality of Life Questionnaire-C30 (Cancer 30items). All items are scored 1 (worse outcome) to 4 (better outcome) or 1 (worse outcome) to 7 (better outcome). All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.	At inclusion
Assess quality of life measured with Quality of Life Questionnaire-Brain Neoplasms 20items (QLQ-BN20)	The quality of life will be measured at the inclusion with Quality of Life Questionnaire - BN20 (Brain Neoplasms 20items). All items are scored 1 (worse outcome) to 4 (better outcome). All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.	At inclusion
Assess quality of life measured with Quality of Life Questionnaire-Cancer 30items (QLQ-C30)	The quality of life will be measured at 3 months with Quality of Life Questionnaire-C30 (Cancer 30items). All items are scored 1 (worse outcome) to 4 (better outcome) or 1 (worse outcome) to 7 (better outcome). All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.	At 3 months after inclusion
Assess quality of life measured with Quality of Life Questionnaire-Brain Neoplasms 20items (QLQ-BN20)	The quality of life will be measured at 3 months with Quality of Life Questionnaire - BN20 (Brain Neoplasms 20items). All items are scored 1 (worse outcome) to 4 (better outcome). All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.	At 3 months after inclusion
Assess quality of life measured with Quality of Life Questionnaire-Cancer 30items (QLQ-C30)	The quality of life will be measured at 6 months with Quality of Life Questionnaire-C30 (Cancer 30items). All items are scored 1 (worse outcome) to 4 (better outcome) or 1 (worse outcome) to 7 (better outcome). All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.	At 6 months after inclusion
Assess quality of life measured with Quality of Life Questionnaire-Brain Neoplasms 20items (QLQ-BN20)	The quality of life will be measured at 6 months with Quality of Life Questionnaire - BN20 (Brain Neoplasms 20items). All items are scored 1 (worse outcome) to 4 (better outcome). All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.	At 6 months after inclusion
Assess quality of life measured with Quality of Life Questionnaire-Cancer 30items (QLQ-C30)	The quality of life will be measured at 12 months with Quality of Life Questionnaire-C30 (Cancer 30items). All items are scored 1 (worse outcome) to 4 (better outcome) or 1 (worse outcome) to 7 (better outcome). All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.	At 12 months after inclusion
Assess quality of life measured with Quality of Life Questionnaire-Brain Neoplasms 20items (QLQ-BN20)	The quality of life will be measured at 12 months with Quality of Life Questionnaire - BN20 (Brain Neoplasms 20items). All items are scored 1 (worse outcome) to 4 (better outcome). All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.	At 12 months after inclusion
Assess quality of life measured with Quality of Life Questionnaire-Cancer 30items (QLQ-C30)	The quality of life will be measured at 18 months with Quality of Life Questionnaire-C30 (Cancer 30items). All items are scored 1 (worse outcome) to 4 (better outcome) or 1 (worse outcome) to 7 (better outcome). All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.	At 18 months after inclusion
Assess quality of life measured with Quality of Life Questionnaire-Brain Neoplasms 20items (QLQ-BN20)	The quality of life will be measured at 18 months with Quality of Life Questionnaire - BN20 (Brain Neoplasms 20items). All items are scored 1 (worse outcome) to 4 (better outcome). All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.	At 18 months after inclusion
Correlate O6-Methylguanine-DNA Methyltransferase (MGMT) promoter methylation status and Overall survival	MGMT promoter methylation status (binary variable, determined by either Polymerase Chain reaction (PCR) or immunohistochemistry)	At 24 months after inclusion

Collaborators and Investigators

• Sponsor: Institut de cancérologie Strasbourg Europe
• Investigators: Principal Investigator: Caroline BUND, Institut de cancerologie Strasbourg Europe

Publications and helpful links

General Publications

• Perry JR, Laperriere N, O'Callaghan CJ, Brandes AA, Menten J, Phillips C, Fay M, Nishikawa R, Cairncross JG, Roa W, Osoba D, Rossiter JP, Sahgal A, Hirte H, Laigle-Donadey F, Franceschi E, Chinot O, Golfinopoulos V, Fariselli L, Wick A, Feuvret L, Back M, Tills M, Winch C, Baumert BG, Wick W, Ding K, Mason WP; Trial Investigators. Short-Course Radiation plus Temozolomide in Elderly Patients with Glioblastoma. N Engl J Med. 2017 Mar 16;376(11):1027-1037. doi: 10.1056/NEJMoa1611977.
• Truc G, Bernier V, Mirjolet C, Dalban C, Mazoyer F, Bonnetain F, Blanchard N, Lagneau E, Maingon P, Noel G. A phase I dose escalation study using simultaneous integrated-boost IMRT with temozolomide in patients with unifocal glioblastoma. Cancer Radiother. 2016 May;20(3):193-8. doi: 10.1016/j.canrad.2015.12.005. Epub 2016 Apr 23.
• Somme F, Bender L, Namer IJ, Noel G, Bund C. Usefulness of 18F-FDOPA PET for the management of primary brain tumors: a systematic review of the literature. Cancer Imaging. 2020 Oct 6;20(1):70. doi: 10.1186/s40644-020-00348-5.

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2023
• Primary Completion (Anticipated): March 1, 2027
• Study Completion (Anticipated): March 1, 2027

Study Registration Dates

• First Submitted: November 28, 2022
• First Submitted That Met QC Criteria: December 7, 2022
• First Posted (Actual): December 16, 2022

Study Record Updates

• Last Update Posted (Estimate): March 6, 2023
• Last Update Submitted That Met QC Criteria: March 3, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: glioblastoma; intensity modulated radiation therapy; 18F-DOPA-PET imaging
• 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: 2021-010

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No