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

Glioblastoma Multiforme, Adult Clinical Trial

— SIB-DOPA  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05653622
• Other study ID #: 2021-010
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: March 1, 2023
• Est. completion date: March 1, 2027

Study information

• Verified date: March 2023
• Source: Institut de cancérologie Strasbourg Europe
• Contact: Manon VOEGELIN
• Phone: +33(0)368339523
• Email: m.voegelin[@]icans.eu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 75
• Est. completion date: March 1, 2027
• Est. primary completion date: March 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme, Adult

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Institut de cancérologie Strasbourg Europe

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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