Glioblastoma MultiformePhase 2GlioMETNCT05608395
11C-methionine in Diagnostics and Management of Glioblastoma Multiforme Patients (GlioMET)
A Phase 2 study testing 11C-Methionine PET/CT in people with Glioblastoma Multiforme, run by Masaryk Memorial Cancer Institute at 1 site in Czechia.
Trial summary
Glioblastoma multiforme (GBM) is the most common primary brain cancer. The treatment of GBM consists of a combination of surgery and subsequent oncological therapy, i.e. radiotherapy, chemotherapy, or combination of both at te same time. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- 11C-Methionine PET/CT
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteCzechia
- Study dates
- 4 Dec 2020to 20 Jun 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The subject is a person with a histologically proven diagnosis of glioblastoma (GB) according to WHO 2016.
- The subject is male or female, aged 18 years or older.
- Performance status (PS) according to ECOG (Eastern Cooperative Oncology Group) 0-2.
- Healed operation wound.
- Post-operative MR up to 72 hours.
- Indication to adjuvant chemoradiotherapy.
Show all 15Show fewer
- Patient has to express his/her informed consent and sign the form before the screening period.
- Detected rapid early progression.
- Patient must achieve following values of laboratory parameters in the peripheral blood during the screening period:
- neutrophiles (total count) ≥1500/mm3
- platelets (total count) ≥100 000/mm3
- hemoglobin ≥ 9,0 g/dL
- serum creatinin ≤1,5x of upper limit of normal, ULN
- total bilirubin 1,5x ULN, unless documented Gilbert's syndrome, for which bilirubin ≤ 3x ULN is permitted
- AST/ALT ≤3x ULN
Who cannot join
- Prior brain surgery.
- Prior radiotherapy targeting brain.
- The history of active/currently treated cancer (solid tumor); the exceptions are: non-melanoma skin cancer, in situ bladder carcinoma, in situ gastric cancer, in situ colorectal carcinoma, in situ cervical carcinoma, in situ breast cancer.
- Any systemic disease or health condition that might posses a risk at anticancer therapy and imaging techniques (MRI, MET PET).
- Patients must not have substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Patients must not have any evidence of ongoing (active) infection (HIV, hepatitis A, B, C).
- Pregnant and/or breastfeeding women.
- Patient who disagree and refuses to sign an Informed consent.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 11C-methionine in Diagnostics and Management of Glioblastoma Multiforme With Rapid Early Progression Patients Prior to Adjuvant Oncological Therapy (GlioMET)
Glioblastoma multiforme (GBM) is the most common primary brain cancer. The treatment of GBM consists of a combination of surgery and subsequent oncological therapy, i.e. radiotherapy, chemotherapy, or combination of both at te same time. If post-operative oncological therapy involves irradiation, magnetic resonance imaging (MRI) is planned. Unfortunately, in some cases, a very early worsening (progression) or return (recurrence) of the disease is observed several weeks after the surgery, i.e. rapid early progression (REP). Radiotherapy planning is based on this MRI in all patients. However, a subset of patients with REP have a less favorable prognosis with this treatment management. The investigators therefore assume that these patients need a more thorough examination to form a precise radiotherapy plan. The project focuses on this group of patients with a less favorable prognosis (with a more aggressive disease). Patients who develop REP within approximately 6 weeks after surgery will have PET/CT (positron emission tomography in combination with computed tomography) examinations using the radiopharmaceutical 11C-methionine in addition to standard practice. PET is one of the most modern methods of molecular imaging, a non-invasive in vivo method that allows physicians to study processes in the human body using radiolabeled radiopharmaceuticals. 11C-methionine is an example of a radiolabeled (carbon 11) amino acid - a source of energy for tumor cells and a building material for new proteins. This radiopharmaceutical is commonly used in the diagnosis of brain tumors and in the evaluation of response to treatment. For patients who undergo this examination, the radiotherapy planning will be adjusted based on it. The purpose of clinical trial is to improve the prospects of patients with REP.
Read the detailed description
Glioblastoma (GB) is the most aggressive diffuse glioma that corresponds to grade 4 based on the 2016 WHO Classification of Tumors of the Central Nervous System. GB is the most common primary brain malignancy with the incidence of 3 per 100,000 persons per year, accounting for 45 % of malignant primary brain tumors and 54 % of all gliomas. Despite the considerable improvements in surgical techniques, which enable more extensive degree of resection, wide application of more precise radiotherapy (RT) and novel chemotherapeutic agents, GB remains an incurable disease with a median survival of 15 months and 3-year overall survival (OS) of less than 10 % in real clinical practice. Clinical trials evaluating the role of modern targeted therapy did not prove superiority of this treatment strategy and results of GB treatment remains poor.
Current standard of care is based on multimodality treatment combining surgery, RT and chemotherapy with alkylating agent temozolomide (TMZ). Standard post-surgery treatment of newly diagnosed GB patients has remained unchanged since implementation of the recommendations of the EORTC 26981-22981/NCIC CE3 trial (Stupp regimen) that finished enrolling patients in 2002 and was published in 2005. Co-administration of TMZ improved survival from 12,1 months (with RT alone) to 14,6 months (with addition of TMZ). Continuing effort how to improve treatment outcomes is urgent clinical as well as research need.
The phenomenon of postoperative REP has only recently been explored with increasingly available MRI for both postsurgery and preRT indication and is currently of high interest. REP diagnosis is based on a comparison of early postoperative MRI findings (up to 72 hours postoperatively) and planning preRT MRI. Our retrospective analysis of 95 patients with GB treated during 2014-2017 revealed that 52% patients developed suspected progression at MRI performed for RT planning purposes. These patients may represent a subset of patients with a particularly aggressive phenotype of GB. It was consistently confirmed that the presence of early recurrence on planning MRI examination was associated with a more aggressive form of glioblastoma and worse overall survival. Higher risk can be expected in patients after fewer radical resections.
Currently, it is not clear what is the optimal approach in patients with REP. Whether to indicate reoperation of recurrence, to choose accelerated RT regimes with or without concurrent chemotherapy or administration of more aggressive and intensive chemotherapy with combined alkylating cytostatics. Treatment of these patients today is not different from patients without REP, and if so, it is purely an individual approach. Clearly, these patients biased previous clinical trials where no routine preRT MRI examination was performed. Currently, these patients are usually excluded from clinical trials, moreover, recent studies often randomize patients after the competition of standard adjuvant chemoRT without any clear progression on the first post chemoRT MRI. REP in MRI planning is a significant negative prognostic factor that should be a stratification factor in future clinical trials. The basic problem is the postoperative prediction of early recurrence.
Amino acid Carbon-11-labeled methionine PET (MET PET) is the most widely studied tracer for molecular imaging in glioma. PET is currently becoming progressively more established part of brain imaging in both pretreatment as well as follow up examination. There is increasing evidence supporting implementation of PET imaging into brain cancer management. Amino acid tracers´ uptake reflects amino acid transport and proteosynthesis which are increased in most types of tumors including gliomas when compared to normal surrounding tissues. Resulted higher tumor-to-normal brain ratio (T/N ratio) provides higher contrast and tumor discrimination comparing to FDG even through lower absolute standard uptake values (SUV). However, because amino acid tracer transport is independent of blood brain barrier breakdown, there is visible PET uptake for tumors that do not enhance on MRI or for aggressive parts of tumor with no MRI contrast uptake yet.
MET PET plays an especially important role in improving diagnostic procedures for treating brain tumors. [11C] Methionine is not taken up by normal brain tissue to a marked degree, and the sensitivity of MET PET for detecting glioma tumors appears to be high. It has been suggested that MET PET may more precisely outline the true extent of viable tumor tissue than MRI, whereas MRI has the capability to better delineate the total extent of associated pathologic changes, such as edema, in adjacent brain areas. MET PET tumor/normal tissue index of 1,3 was considered the threshold for malignant activity based on correlation to stereotactic histopathology examination. Usage of MET PET is limited by its short half-life to centers with its own cyclotron enabling the manufacture of radiopharmaceuticals. Patients with REP of GB need to start oncological treatment as soon as possible and it is not ethical to wait for other commercially available radiopharmaceuticals (FET, FLT and others) that have a longer half-life but are only available in limited ordering schedule. In the comprehensive neurooncological centers, however, the individual rapid preparation of methionine tracer, the most studied substance in brain tumors, is the unique option how to improve outcomes of patients with REP, particularly aggressive GB.
- Conditions
- Glioblastoma Multiforme
- Being tested
- 11C-Methionine PET/CT
- Keywords
- rapid early progression, 11C-Methionine, MET-PET/CT
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
11C-Methionine PET/CTDrug
Also called Methionine application
11C-Methionine PET/CT will be applied in patients in 11C-Methionine PET/CT Arm, based on planning MRI, prior chemo/radiotherapy (2 weeks prior C1D1)
| Study group | Role | What they receive |
|---|---|---|
| 11C-Methionine PET/CT Arm | Experimental | The cohort consists of patients:
* diagnosed with GB
* with confirmed REP
* indicated for adjuvant chemoradiotherapy
* will undergo the 11C-MET PET/CT Receives: Drug: 11C-Methionine PET/CT |
| Arm A-historical | No intervention | The cohort consists of a historical group of patients collected in the period 2014-2018: * with diagnosed GB * with confirmed REP * were indicated for adjuvant chemoradiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival (PFS) in 11C-Methionine PET/CT Arm vs. PFS in Arm Ahist
PFS in 11C-Methionine PET/CT Arm vs. PFS in historical cohort (Arm A/hist./). PFS timeframe = start of radiotherapy / progression of disease or death.
Measured: 44 months
Secondary outcomes (11)
Rapid-Early-Progression incidence
Prospective evaluation of the incidence of Rapid-Early-Progression (REP) on planning MR in patients with GB indicated for adjuvant chemoradiotherapy.
Measured: 38 months
Overall survival in 11C-Methionine PET/CT Arm vs. overall survival in Arm Ahist
OS in 11C-Methionine PET/CT Arm compared to the historical retrospective group (arm Ahist). OS timeframe = surgery / death related to glioblastoma multiforme
Measured: 44 months
Progression free survival in 11C-Methionine PET/CT Arm vs. progression free survival in Arm Ahist.
Median PFS in arm A > median PFS in arm Ahist by ≥3.1 months. Progression free survival (PFS) is defined as the time from initiation of radiotherapy to the occurrence of progression or death.
Measured: 44 months
Biomarkers I
Immunohistochemical analysis of GFAP, Ki-67, IDH1, ATRX, and PDL1. GFAP: positive/negative/focal positive Ki-67, IDH1: positive/negative ATRX loss of expression: positive/negative PDL1 protein expression: positive/negative
Measured: 38 months
Biomarkers II
Mutational status of TERT and IDH2: mutated/wild-type
Measured: 38 months
Biomarkers III
Sanger sequencing of IDH1 in IDH1 IHC positive patients: mutated/wild-type
Measured: 38 months
Biomarkers IV
MGMT promotor methylation status: ≥25% = methylated/<25% = unmethylated
Measured: 38 months
Biomarkers V
1p/19q co-deletion: positive/negative
Measured: 38 months
Patterns-of-failure analysis
Evaluation of spatial patterns of failure (PoF; central (V95% ≥ 95%)/in-field (80% ≤ V95%)/marginal (20% ≤V95% < 80%)/distant (V95% < 20%)) in patients with REP (arm A) compared to the historical retrospective group (arm Ahist). In the case of MULTIFOCAL progression, each PD is evaluated independently, i.e. patient could have one central and one distal PD. In subsequent statistical analysis, each PD is evaluated independently. PoF could be performed even in death subjects, if MR describing the progression is available.
Measured: 44 months
Quality of Life assessment using the standardized European Organisation for Research and Treatment of Cancer (EORTC) questionnaire QLQ-C30
Quality of life will be assessed using standardized questionnaire: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 v.3.0 during screening period, visits 2, 4, 6, 8, 10, 12 (End-Of-Treatment) and during follow-up period every 3 months (+/- 1 week) up to progression of the disease.
Measured: 44 months
Quality of Life assessment using the standardized European Organisation for Research and Treatment of Cancer (EORTC) Quality of life questionnaire-BN20
Quality of life will be assessed using standardized questionnaire: additional module Brain cancer European Organisation for Research and Treatment of Cancer Quality of life questionnaire BN20 during screening period, visits 2, 4, 6, 8, 10, 12 (End-Of-Treatment) and during follow-up period every 3 months (+/- 1 week) up to the disease.
Measured: 44 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2022
- Study start4 Dec 2020
- Primary completion20 Jun 2024
- Study completion20 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 11C-Methionine PET/CT Arm is to be compared to historical cohort A(hist.).
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masaryk Memorial Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Radek Lakomy, MD, Ph.D., Principal investigator, Masaryk Memorial Cancer Institute, Dept. of Comprehensive Cancer Care
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05608395
- Sponsor's protocol ID
- MOU-2020-01
- Acronym
- GlioMET
- Status last verified
- Sep 2025
- First submitted
- 25 Feb 2021
- Last updated
- 25 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lakomy R, Fadrus P, Slampa P, Svoboda T, Kren L, Lzicarova E, Belanova R, Sikova I, Poprach A, Schneiderova M, Prochazkova M, Sana J, Slaby O, Smrcka M, Vyzula R, Svoboda M. [Multimodal treatment of glioblastoma multiforme: results of 86 consecutive patients diagnosed in period 2003-2009]. Klin Onkol. 2011;24(2):112-20. Czech.
PubMed 21644366Weller M, van den Bent M, Tonn JC, Stupp R, Preusser M, Cohen-Jonathan-Moyal E, Henriksson R, Le Rhun E, Balana C, Chinot O, Bendszus M, Reijneveld JC, Dhermain F, French P, Marosi C, Watts C, Oberg I, Pilkington G, Baumert BG, Taphoorn MJB, Hegi M, Westphal M, Reifenberger G, Soffietti R, Wick W; European Association for Neuro-Oncology (EANO) Task Force on Gliomas. European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol. 2017 Jun;18(6):e315-e329. doi: 10.1016/S1470-2045(17)30194-8. Epub 2017 May 5.
PubMed 28483413Kazda T, Dziacky A, Burkon P, Pospisil P, Slavik M, Rehak Z, Jancalek R, Slampa P, Slaby O, Lakomy R. Radiotherapy of Glioblastoma 15 Years after the Landmark Stupp's Trial: More Controversies than Standards? Radiol Oncol. 2018 Jun 6;52(2):121-128. doi: 10.2478/raon-2018-0023. eCollection 2018 Jun.
PubMed 30018514Blumenthal DT, Gorlia T, Gilbert MR, Kim MM, Burt Nabors L, Mason WP, Hegi ME, Zhang P, Golfinopoulos V, Perry JR, Hyun Nam D, Erridge SC, Corn BW, Mirimanoff RO, Brown PD, Baumert BG, Mehta MP, van den Bent MJ, Reardon DA, Weller M, Stupp R. Is more better? The impact of extended adjuvant temozolomide in newly diagnosed glioblastoma: a secondary analysis of EORTC and NRG Oncology/RTOG. Neuro Oncol. 2017 Aug 1;19(8):1119-1126. doi: 10.1093/neuonc/nox025.
PubMed 28371907Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330.
PubMed 15758009Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups; National Cancer Institute of Canada Clinical Trials Group. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009 May;10(5):459-66. doi: 10.1016/S1470-2045(09)70025-7. Epub 2009 Mar 9.
PubMed 19269895Pirzkall A, McGue C, Saraswathy S, Cha S, Liu R, Vandenberg S, Lamborn KR, Berger MS, Chang SM, Nelson SJ. Tumor regrowth between surgery and initiation of adjuvant therapy in patients with newly diagnosed glioblastoma. Neuro Oncol. 2009 Dec;11(6):842-52. doi: 10.1215/15228517-2009-005.
PubMed 19229057Wee CW, Kim E, Kim TM, Park CK, Kim JW, Choi SH, Yoo RE, Lee ST, Kim IH. Impact of interim progression during the surgery-to-radiotherapy interval and its predictors in glioblastoma treated with temozolomide-based radiochemotherapy. J Neurooncol. 2017 Aug;134(1):169-175. doi: 10.1007/s11060-017-2505-x. Epub 2017 May 25.
PubMed 28547592Merkel A, Soeldner D, Wendl C, Urkan D, Kuramatsu JB, Seliger C, Proescholdt M, Eyupoglu IY, Hau P, Uhl M. Early postoperative tumor progression predicts clinical outcome in glioblastoma-implication for clinical trials. J Neurooncol. 2017 Apr;132(2):249-254. doi: 10.1007/s11060-016-2362-z. Epub 2017 Jan 18.
PubMed 28101701Katsanos AH, Alexiou GA, Fotopoulos AD, Jabbour P, Kyritsis AP, Sioka C. Performance of 18F-FDG, 11C-Methionine, and 18F-FET PET for Glioma Grading: A Meta-analysis. Clin Nucl Med. 2019 Nov;44(11):864-869. doi: 10.1097/RLU.0000000000002654.
PubMed 31205150Grosu AL, Weber WA, Riedel E, Jeremic B, Nieder C, Franz M, Gumprecht H, Jaeger R, Schwaiger M, Molls M. L-(methyl-11C) methionine positron emission tomography for target delineation in resected high-grade gliomas before radiotherapy. Int J Radiat Oncol Biol Phys. 2005 Sep 1;63(1):64-74. doi: 10.1016/j.ijrobp.2005.01.045.
PubMed 16111573Matsuo M, Miwa K, Tanaka O, Shinoda J, Nishibori H, Tsuge Y, Yano H, Iwama T, Hayashi S, Hoshi H, Yamada J, Kanematsu M, Aoyama H. Impact of [11C]methionine positron emission tomography for target definition of glioblastoma multiforme in radiation therapy planning. Int J Radiat Oncol Biol Phys. 2012 Jan 1;82(1):83-9. doi: 10.1016/j.ijrobp.2010.09.020. Epub 2010 Nov 20.
PubMed 21095072Lakomy R, Lojova M, Souckova L, Hynkova L, Polachova K, Vasina J, Demlova R, Poprach A, Sana J, Prochazka T, Smrcka M, Fadrus P, Jancalek R, Selingerova I, Belanova R, Slampa P, Pospisil P, Kazda T. 11C-methionine in the diagnostics and management of glioblastoma patients with rapid early progression: nonrandomized, open label, prospective clinical trial (GlioMET). BMC Cancer. 2024 Jun 15;24(1):736. doi: 10.1186/s12885-024-12469-2.
PubMed 38879476
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 11C-methionine in Diagnostics and Management of Glioblastoma Multiforme With Rapid Early Progression Patients Prior to Adjuvant Oncological Therapy (GlioMET)
- ClinicalTrials.gov ID
- NCT05608395
- Acronym / sponsor ID
- GlioMET / MOU-2020-01
- Conditions
- Glioblastoma Multiforme
- Keywords
- rapid early progression, 11C-Methionine, MET-PET/CT
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Masaryk Memorial Cancer InstituteUniversity, hospital or other
- Study start
- 4 Dec 2020 (actual)
- Primary completion
- 20 Jun 2024 (actual)
- Study completion
- 20 Jun 2024 (actual)
- First posted
- 8 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Glioblastoma multiforme (GBM) is the most common primary brain cancer. The treatment of GBM consists of a combination of surgery and subsequent oncological therapy, i.e. radiotherapy, chemotherapy, or combination of both at te same time. If post-operative oncological therapy involves irradiation, magnetic resonance imaging (MRI) is planned. Unfortunately, in some cases, a very early worsening (progression) or return (recurrence) of the disease is observed several weeks after the surgery, i.e. rapid early progression (REP). Radiotherapy planning is based on this MRI in all patients. However, a subset of patients with REP have a less favorable prognosis with this treatment management. The investigators therefore assume that these patients need a more thorough examination to form a precise radiotherapy plan. The project focuses on this group of patients with a less favorable prognosis (with a more aggressive disease). Patients who develop REP within approximately 6 weeks after surgery will have PET/CT (positron emission tomography in combination with computed tomography) examinations using the radiopharmaceutical 11C-methionine in addition to standard practice. PET is one of the most modern methods of molecular imaging, a non-invasive in vivo method that allows physicians to study processes in the human body using radiolabeled radiopharmaceuticals. 11C-methionine is an example of a radiolabeled (carbon 11) amino acid - a source of energy for tumor cells and a building material for new proteins. This radiopharmaceutical is commonly used in the diagnosis of brain tumors and in the evaluation of response to treatment. For patients who undergo this examination, the radiotherapy planning will be adjusted based on it. The purpose of clinical trial is to improve the prospects of patients with REP.
Detailed description
Glioblastoma (GB) is the most aggressive diffuse glioma that corresponds to grade 4 based on the 2016 WHO Classification of Tumors of the Central Nervous System. GB is the most common primary brain malignancy with the incidence of 3 per 100,000 persons per year, accounting for 45 % of malignant primary brain tumors and 54 % of all gliomas. Despite the considerable improvements in surgical techniques, which enable more extensive degree of resection, wide application of more precise radiotherapy (RT) and novel chemotherapeutic agents, GB remains an incurable disease with a median survival of 15 months and 3-year overall survival (OS) of less than 10 % in real clinical practice. Clinical trials evaluating the role of modern targeted therapy did not prove superiority of this treatment strategy and results of GB treatment remains poor.
Current standard of care is based on multimodality treatment combining surgery, RT and chemotherapy with alkylating agent temozolomide (TMZ). Standard post-surgery treatment of newly diagnosed GB patients has remained unchanged since implementation of the recommendations of the EORTC 26981-22981/NCIC CE3 trial (Stupp regimen) that finished enrolling patients in 2002 and was published in 2005. Co-administration of TMZ improved survival from 12,1 months (with RT alone) to 14,6 months (with addition of TMZ). Continuing effort how to improve treatment outcomes is urgent clinical as well as research need.
The phenomenon of postoperative REP has only recently been explored with increasingly available MRI for both postsurgery and preRT indication and is currently of high interest. REP diagnosis is based on a comparison of early postoperative MRI findings (up to 72 hours postoperatively) and planning preRT MRI. Our retrospective analysis of 95 patients with GB treated during 2014-2017 revealed that 52% patients developed suspected progression at MRI performed for RT planning purposes. These patients may represent a subset of patients with a particularly aggressive phenotype of GB. It was consistently confirmed that the presence of early recurrence on planning MRI examination was associated with a more aggressive form of glioblastoma and worse overall survival. Higher risk can be expected in patients after fewer radical resections.
Currently, it is not clear what is the optimal approach in patients with REP. Whether to indicate reoperation of recurrence, to choose accelerated RT regimes with or without concurrent chemotherapy or administration of more aggressive and intensive chemotherapy with combined alkylating cytostatics. Treatment of these patients today is not different from patients without REP, and if so, it is purely an individual approach. Clearly, these patients biased previous clinical trials where no routine preRT MRI examination was performed. Currently, these patients are usually excluded from clinical trials, moreover, recent studies often randomize patients after the competition of standard adjuvant chemoRT without any clear progression on the first post chemoRT MRI. REP in MRI planning is a significant negative prognostic factor that should be a stratification factor in future clinical trials. The basic problem is the postoperative prediction of early recurrence.
Amino acid Carbon-11-labeled methionine PET (MET PET) is the most widely studied tracer for molecular imaging in glioma. PET is currently becoming progressively more established part of brain imaging in both pretreatment as well as follow up examination. There is increasing evidence supporting implementation of PET imaging into brain cancer management. Amino acid tracers´ uptake reflects amino acid transport and proteosynthesis which are increased in most types of tumors including gliomas when compared to normal surrounding tissues. Resulted higher tumor-to-normal brain ratio (T/N ratio) provides higher contrast and tumor discrimination comparing to FDG even through lower absolute standard uptake values (SUV). However, because amino acid tracer transport is independent of blood brain barrier breakdown, there is visible PET uptake for tumors that do not enhance on MRI or for aggressive parts of tumor with no MRI contrast uptake yet.
MET PET plays an especially important role in improving diagnostic procedures for treating brain tumors. [11C] Methionine is not taken up by normal brain tissue to a marked degree, and the sensitivity of MET PET for detecting glioma tumors appears to be high. It has been suggested that MET PET may more precisely outline the true extent of viable tumor tissue than MRI, whereas MRI has the capability to better delineate the total extent of associated pathologic changes, such as edema, in adjacent brain areas. MET PET tumor/normal tissue index of 1,3 was considered the threshold for malignant activity based on correlation to stereotactic histopathology examination. Usage of MET PET is limited by its short half-life to centers with its own cyclotron enabling the manufacture of radiopharmaceuticals. Patients with REP of GB need to start oncological treatment as soon as possible and it is not ethical to wait for other commercially available radiopharmaceuticals (FET, FLT and others) that have a longer half-life but are only available in limited ordering schedule. In the comprehensive neurooncological centers, however, the individual rapid preparation of methionine tracer, the most studied substance in brain tumors, is the unique option how to improve outcomes of patients with REP, particularly aggressive GB.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 11C-Methionine PET/CT Arm is to be compared to historical cohort A(hist.).
| Arm | Type | Receives |
|---|---|---|
| 11C-Methionine PET/CT Arm | Experimental | Drug: 11C-Methionine PET/CTThe cohort consists of patients: * diagnosed with GB * with confirmed REP * indicated for adjuvant chemoradiotherapy * will undergo the 11C-MET PET/CT |
| Arm A-historical | No intervention | –The cohort consists of a historical group of patients collected in the period 2014-2018: * with diagnosed GB * with confirmed REP * were indicated for adjuvant chemoradiotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- The subject is a person with a histologically proven diagnosis of glioblastoma (GB) according to WHO 2016.
- The subject is male or female, aged 18 years or older.
- Performance status (PS) according to ECOG (Eastern Cooperative Oncology Group) 0-2.
- Healed operation wound.
- Post-operative MR up to 72 hours.
Key exclusion criteria (8 listed)
- Prior brain surgery.
- Prior radiotherapy targeting brain.
- The history of active/currently treated cancer (solid tumor); the exceptions are: non-melanoma skin cancer, in situ bladder carcinoma, in situ gastric cancer, in situ colorectal carcinoma, in situ cervical carcinoma, in situ breast cancer.
- Any systemic disease or health condition that might posses a risk at anticancer therapy and imaging techniques (MRI, MET PET).
- Patients must not have substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 11C-Methionine PET/CTAlso: Methionine application11C-Methionine PET/CT will be applied in patients in 11C-Methionine PET/CT Arm, based on planning MRI, prior chemo/radiotherapy (2 weeks prior C1D1) | Drug | 11C-Methionine PET/CT Arm |
Primary outcome
Progression free survival (PFS) in 11C-Methionine PET/CT Arm vs. PFS in Arm Ahist
Time frame: 44 months
PFS in 11C-Methionine PET/CT Arm vs. PFS in historical cohort (Arm A/hist./). PFS timeframe = start of radiotherapy / progression of disease or death.
11 secondary outcomes
Rapid-Early-Progression incidence
Time frame: 38 months
Overall survival in 11C-Methionine PET/CT Arm vs. overall survival in Arm Ahist
Time frame: 44 months
Progression free survival in 11C-Methionine PET/CT Arm vs. progression free survival in Arm Ahist.
Time frame: 44 months
Biomarkers I
Time frame: 38 months
Biomarkers II
Time frame: 38 months
Biomarkers III
Time frame: 38 months
Biomarkers IV
Time frame: 38 months
Biomarkers V
Time frame: 38 months
Patterns-of-failure analysis
Time frame: 44 months
Quality of Life assessment using the standardized European Organisation for Research and Treatment of Cancer (EORTC) questionnaire QLQ-C30
Time frame: 44 months
Quality of Life assessment using the standardized European Organisation for Research and Treatment of Cancer (EORTC) Quality of life questionnaire-BN20
Time frame: 44 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2025.
- Background: PubMed 21644366Lakomy R, Fadrus P, Slampa P, Svoboda T, Kren L, Lzicarova E, Belanova R, Sikova I, Poprach A, Schneiderova M, Prochazkova M, Sana J, Slaby O, Smrcka M, Vyzula R, Svoboda M. [Multimodal treatment of glioblastoma multiforme: results of 86 consecutive patients diagnosed in period 2003-2009]. Klin Onkol. 2011;24(2):112-20. Czech.
- Background: PubMed 28483413Weller M, van den Bent M, Tonn JC, Stupp R, Preusser M, Cohen-Jonathan-Moyal E, Henriksson R, Le Rhun E, Balana C, Chinot O, Bendszus M, Reijneveld JC, Dhermain F, French P, Marosi C, Watts C, Oberg I, Pilkington G, Baumert BG, Taphoorn MJB, Hegi M, Westphal M, Reifenberger G, Soffietti R, Wick W; European Association for Neuro-Oncology (EANO) Task Force on Gliomas. European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol. 2017 Jun;18(6):e315-e329. doi: 10.1016/S1470-2045(17)30194-8. Epub 2017 May 5.
- Background: PubMed 30018514Kazda T, Dziacky A, Burkon P, Pospisil P, Slavik M, Rehak Z, Jancalek R, Slampa P, Slaby O, Lakomy R. Radiotherapy of Glioblastoma 15 Years after the Landmark Stupp's Trial: More Controversies than Standards? Radiol Oncol. 2018 Jun 6;52(2):121-128. doi: 10.2478/raon-2018-0023. eCollection 2018 Jun.
- Background: PubMed 28371907Blumenthal DT, Gorlia T, Gilbert MR, Kim MM, Burt Nabors L, Mason WP, Hegi ME, Zhang P, Golfinopoulos V, Perry JR, Hyun Nam D, Erridge SC, Corn BW, Mirimanoff RO, Brown PD, Baumert BG, Mehta MP, van den Bent MJ, Reardon DA, Weller M, Stupp R. Is more better? The impact of extended adjuvant temozolomide in newly diagnosed glioblastoma: a secondary analysis of EORTC and NRG Oncology/RTOG. Neuro Oncol. 2017 Aug 1;19(8):1119-1126. doi: 10.1093/neuonc/nox025.
- Background: PubMed 15758009Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330.
- Background: PubMed 19269895Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups; National Cancer Institute of Canada Clinical Trials Group. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009 May;10(5):459-66. doi: 10.1016/S1470-2045(09)70025-7. Epub 2009 Mar 9.
- Background: PubMed 19229057Pirzkall A, McGue C, Saraswathy S, Cha S, Liu R, Vandenberg S, Lamborn KR, Berger MS, Chang SM, Nelson SJ. Tumor regrowth between surgery and initiation of adjuvant therapy in patients with newly diagnosed glioblastoma. Neuro Oncol. 2009 Dec;11(6):842-52. doi: 10.1215/15228517-2009-005.
- Background: PubMed 28547592Wee CW, Kim E, Kim TM, Park CK, Kim JW, Choi SH, Yoo RE, Lee ST, Kim IH. Impact of interim progression during the surgery-to-radiotherapy interval and its predictors in glioblastoma treated with temozolomide-based radiochemotherapy. J Neurooncol. 2017 Aug;134(1):169-175. doi: 10.1007/s11060-017-2505-x. Epub 2017 May 25.
- Background: PubMed 28101701Merkel A, Soeldner D, Wendl C, Urkan D, Kuramatsu JB, Seliger C, Proescholdt M, Eyupoglu IY, Hau P, Uhl M. Early postoperative tumor progression predicts clinical outcome in glioblastoma-implication for clinical trials. J Neurooncol. 2017 Apr;132(2):249-254. doi: 10.1007/s11060-016-2362-z. Epub 2017 Jan 18.
- Background: PubMed 31205150Katsanos AH, Alexiou GA, Fotopoulos AD, Jabbour P, Kyritsis AP, Sioka C. Performance of 18F-FDG, 11C-Methionine, and 18F-FET PET for Glioma Grading: A Meta-analysis. Clin Nucl Med. 2019 Nov;44(11):864-869. doi: 10.1097/RLU.0000000000002654.
- Background: PubMed 16111573Grosu AL, Weber WA, Riedel E, Jeremic B, Nieder C, Franz M, Gumprecht H, Jaeger R, Schwaiger M, Molls M. L-(methyl-11C) methionine positron emission tomography for target delineation in resected high-grade gliomas before radiotherapy. Int J Radiat Oncol Biol Phys. 2005 Sep 1;63(1):64-74. doi: 10.1016/j.ijrobp.2005.01.045.
- Background: PubMed 21095072Matsuo M, Miwa K, Tanaka O, Shinoda J, Nishibori H, Tsuge Y, Yano H, Iwama T, Hayashi S, Hoshi H, Yamada J, Kanematsu M, Aoyama H. Impact of [11C]methionine positron emission tomography for target definition of glioblastoma multiforme in radiation therapy planning. Int J Radiat Oncol Biol Phys. 2012 Jan 1;82(1):83-9. doi: 10.1016/j.ijrobp.2010.09.020. Epub 2010 Nov 20.
- Individual participant dataSharing planned: No
Related trials for Glioblastoma Multiforme
Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
Glioblastoma
RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
Glioblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Active, not recruitingPhase 1
Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma
Glioblastoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Radek Lakomy, MD, Ph.D. principal investigator
Masaryk Memorial Cancer Institute, Dept. of Comprehensive Cancer Care
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 11C-Methionine PET/CT in people with Glioblastoma Multiforme, run by Masaryk Memorial Cancer Institute at 1 site in Czechia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (PFS) in 11C-Methionine PET/CT Arm vs. PFS in Arm Ahist (time frame: 44 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05608395, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2025.