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

Study Overview
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Brief Summary
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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.

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

Conditions
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Glioblastoma Multiforme, Adult

Intervention / Treatment
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* Procedure: Integrated boost technique (SIB) guided by PET FDOPA


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glioblastoma, intensity modulated radiation therapy, 18F-DOPA-PET imaging