Long-term Cognitive and Functional Impact of Proton-therapy or Modern Fractionated Radiotherapy in Cavernous Sinus Meningioma: An Open-label Randomized 1:1 Phase III Study
COG-PROTON-01
1 other identifier
interventional
160
1 country
13
Brief Summary
Cavernous sinus meningiomas are close to optic nerve, pituitary gland, cranial nerve, and hippocampi. The doses delivered to these structures are crucial and radiotherapy of cavernous sinus meningiomas exposes patients to late secondary effects (pituitary deficit, nerve palsy, cognitive impairment…). In 2012, Gondi reported that a dose given to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. There is no published or recruiting prospective study evaluating the impact of proton-therapy or conventional irradiation on neurocognitive function for meningioma patients. Notably, long-term cognitive or ocular impact of these modern irradiation schemes remains poorly known. Yet, these patients had a long life-expectancy, and are at risk of developing long-term sequelae. Thus, according to its ballistic advantage, an improvement of patient functional outcomes and a reduction of neurocognitive long-term toxicity are expected if tissue sparing proton-therapy is used. In this context, a randomized prospective study, evaluating long-term toxicity of these two irradiation modalities (Proton Therapy (PRT) and photon radiotherapy (XRT)) seems crucial to further assess proton-therapy indication for these patients. Although literature reports excellent outcomes for intracranial meningioma patients treated by proton-therapy, none of the eight retrospective studies found in the literature used an accurate and full evaluation of long-term toxicity
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Feb 2024
Longer than P75 for not_applicable
13 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 31, 2023
CompletedFirst Posted
Study publicly available on registry
June 8, 2023
CompletedStudy Start
First participant enrolled
February 26, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2032
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 1, 2032
September 29, 2025
September 1, 2025
7.9 years
May 31, 2023
September 24, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
functional deterioration evaluated by individual neurocognitive test scores
Neurocognitive deterioration defined as the occurrence of cognitive impairment (a total of 5 impaired z-scores (17 z-scores for 6 different tests)
5 years
Study Arms (2)
proton-therapy
EXPERIMENTALProton pencil-beam-scanning irradiation (50,4 Gy (RBE) in 28 fractions)
photon radiotherapy
ACTIVE COMPARATORIntensity modulated radiotherapy with or without stereotactic positioning (50,4 Gy in 28 fractions)
Interventions
Proton pencil-beam-scanning irradiation (50,4 Gy (RBE) in 28 fractions)
Intensity modulated radiotherapy with or without stereotactic positioning (50,4 Gy in 28 fractions)
Eligibility Criteria
You may qualify if:
- Cavernous sinus meningioma for which clinical target volume is larger than 3 centimeters
- Anterior skull base meningioma, invading by contiguity the cavernous sinus can be included
- Histologic proven Grade I meningioma
- Meningioma for which biopsy is not safely achievable and for which growing and imaging criteria are in favour of grade I meningioma can be included
- Age \>18 years and ≤70 years
- Indication of irradiation validated by a pluridisciplinary meeting
- Adjuvant or exclusive irradiation is allowed.
- Use of conventional fractionation: 1.8Gy (RBE)/fraction
- Signed informed consent form
- WHO Performance status equal to 0 or 1
- Patient affiliated to the French social health insurance
- MoCA score ≥ cut-off of GRECOGVASC normative data (Roussel, 2016, cf annexe 1)
- Patient whose neuropsychological abilities allow to follow the requirements of the protocol
You may not qualify if:
- Patient with mutation in a known predisposition gene (NF-2, SMARCE-1…)
- Cerebrovascular pathology, presence of other tumors of the nervous system, congenital malformations of the nervous system, multiple sclerosis, Parkinson's disease and other dementias, organic psychosis (other than dementia), schizophrenia, and neurodegenerative disease
- Radiosurgery, hypofractionated regimen
- Other localization than cavernous sinus
- Histologic proven Grade II or III meningioma
- Patient with unadjusted antiepileptic drug
- Contraindication to MRI
- Patient with a history of brain irradiation
- Patient with a history of cancer in the last five years (excluding skin baso-cellular carcinoma)
- Pregnant/breastfeeding woman
- Any geographical conditions, social and associated psychopathology that may compromise the patient's ability to participate in the study
- Participation in a therapeutic trial for less than 30 days
- Patient deprived of freedom or under guardianship
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Centre Francois Baclesselead
- National Cancer Institute, Francecollaborator
Study Sites (13)
Centre Francois Baclesse
Caen, 14000, France
Hopital d'Instruction des Armées PERCY
Clamart, France
CHU Grenoble-Alpes
Grenoble, France
Centre Guillaume le Conquerant
Le Havre, France
Centre Léon Bérard
Lyon, France
Hospices civils de Lyon
Lyon, France
Centre Antoine Lacassagne
Nice, France
Hôpital Pitié Salpétrière
Paris, France
Institut Curie
Paris, France
Institut Curie
Saint-Cloud, France
Centre Paul Strauss
Strasbourg, France
IUCT
Toulouse, France
Gustave Rousy
Villejuif, France
Related Publications (1)
Lesueur P, Clarisse B, Lequesne J, Licaj I, Feuvret L, Stefan D, Ricard D, Noel G, Balosso J, Lange M, Capel A, Durand-Zaleski I, Castera M, Legrand B, Goliot N, Hedou C, Grellard JM, Valable S. Proton therapy versus conventional radiotherapy for the treatment of cavernous sinus benign meningioma, a randomized controlled phase III study protocol (COG-PROTON-01). BMC Cancer. 2024 Dec 30;24(1):1594. doi: 10.1186/s12885-024-13353-9.
PMID: 39736544DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 31, 2023
First Posted
June 8, 2023
Study Start
February 26, 2024
Primary Completion (Estimated)
February 1, 2032
Study Completion (Estimated)
August 1, 2032
Last Updated
September 29, 2025
Record last verified: 2025-09
Data Sharing
- IPD Sharing
- Will not share