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

Cognitive Impairment Clinical Trial

— COG-PROTON-01  

Official title:

Long-term Cognitive and Functional Impact of Proton-therapy or Modern Fractionated Radiotherapy in Cavernous Sinus Meningioma

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05895344
• Other study ID #: 2023-A00401-44
• Status: Not yet recruiting
• Phase: N/A
• Start date: August 2023
• Est. completion date: August 2032

Study information

• Verified date: May 2023
• Source: Centre Francois Baclesse
• Contact: Paul LESUEUR, MD
• Phone: +33 2 31 45 50 50
• Email: p.lesueur[@]baclesse.unicancer.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 160
• Est. completion date: August 2032
• Est. primary completion date: February 2032
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• 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 <60 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Cavernous Sinus Meningioma
• Cognitive Impairment
• Meningioma

Intervention

Radiation:
• Proton-therapy
Proton pencil-beam-scanning irradiation (50,4 Gy (RBE) in 28 fractions)
• Photon radiotherapy
Intensity modulated radiotherapy with or without stereotactic positioning (50,4 Gy in 28 fractions)

Locations

Country	Name	City	State
France	Centre François Baclesse	Caen
France	Hopital d'Instruction des Armées PERCY	Clamart
France	Centre Antoine Lacassagne	Nice
France	Hôpital Pitié Salpétrière	Paris
France	Institut Curie	Paris
France	Centre Paul Strauss	Strasbourg
France	IUCT	Toulouse

Sponsors (2)

Lead Sponsor	Collaborator
Centre Francois Baclesse	National Cancer Institute, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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