Androcur® (Cyproterone Acetate) and Meningioma Development: a Genotype-environment Association Study

Study Overview
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Brief Summary
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The primary objective of the study is to create a biobank of oral smears permitting to identify the genetic locus/loci associated with an increased risk to develop meningiomas after cyproterone acetate (CPA) (Androcur®) treatment, using a GWAS approach. As the secondary objectives, the study aims: to evaluate the importance of the genetic susceptibility. to record the frequence of homonodependant cancers occuring in female patients with Androcur® associated meningioma and in their first-degree relatives. to describe clinical, radiological, histological characteristics of the patients who have developed meningioma after cyproterone acetate exposure.

Detailed Description
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The increased risk to develop a meningioma has recently been established for patients received the cyproterone acetate. The investigators observed several familial cases of CPA related meningiomas which suggest a strong genetic factor modulating the risk to develop meningiomas in patients who exposed to CPA. The aim of this study is to generate a biobank permitting, in future studies, to identify the genetic locus/loci associated with an increased risk to develop meningiomas after CPA (Androcur®) treatment, using a GWAS approach. Enrollment of patients will occur at hospitals where the patients will be treated and also via social networking sites such as Facebook. There will be 4 groups of subjects. Five hundred patients will be enrolled in each group targeting 2000 patients in total, among which 1000 patients (Groupe 1 and Groupe 2) will participate in the biobank. Six centers in 5 university hospitals of APHP (Pitié-Salpêtrière, Ambroise Paré, Cochin, Lariboisière, Saint-Antoine) will be involved in the study. La duration of enrollment will be 24 months. The participation duration for each subject will be 1 hour. Statistics analysis method: SAS 9.1.3.

Official Title
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Androcur® (Cyproterone Acetate) and Meningioma Development: a Genotype-environment Association Study

Conditions
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Meningioma

Intervention / Treatment
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* Procedure: oral smears


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ⩾18 years; Non-opposition opinion obtained during the first phone call at the beginning of the study; Covered by the french social security scheme. For the group 1: Meningioma diagnosed by medical imaging and confirmed histologically if surgery occurred; Cyproterone acetate taken for at least 6 months, 25 mg par day and 20 day by month (cumulated dose ⩾ 3 000mg). For the group 2: Cyproterone acetate taken for at least 5 years with dose of 50 mg per day and 20 day by month, or a cumulated dose corresponding to a longer period (⩾ 30 000mg); Normal result of RMI examination performed after at least 5 years treatment by cyproterone acetate. For the group 3 : Subject who has never taken cyproterone acetate; Meningioma diagnosed by medical imaging examination and confirmed histologically if surgery occured. For the group 4 : Subject who has never taken cyproterone acetate; Subject never diagnosed with meningioma. Exclusion Criteria: Subject under tutoraship; Subject refusal; Communication difficulties such as: language barriers, serious problems of hearing without a hearing instrument, cognitive troubles... ; Foreign subject under AME scheme (a french social system).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| group 1: Exposed to CPA + Meningioma<br>Meningioma diagnosed in women by medical imaging examination and confirmed histologically if surgery is performed. Cyproterone acetate taken for at least 6 months. | Procedure: oral smears<br>* oral smears<br>|
| group 2: Exposed to CPA without Meningioma<br>Women exposed to Cyproterone acetate without developing any meningioma Absence of meningioma assessed by a normal cerebral MRI . Cyproterone acetate taken for at least 5 years. | Procedure: oral smears<br>* oral smears<br>|
| group 3: Not exposed to CPA, Meningioma diagnosed<br>Meningioma in women not exposed to cyproterone acetate. Meningioma diagnosed by medical imaging examination and confirmed histologically if surgery was necessary. Never exposed to cyproterone acetate. | |
| group 4: General population<br>Subjects (women) never diagnosed with meningioma and not exposed to cyproterone acetate. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of enrolled patients for smear samples | Number of enrolled patients in the study with good quality of smear samples. | at the end of study, an average of 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of family cases of meningioma | Number of family cases of meningioma occurrence will be noted in each group. | at the end of study, an average of 2 years | 
| Occurrence of meningioma in first-degree relatives | Number of occurrence of meningioma will be collected for: in first-degree relatives of index case in each group. in first-degree relatives exposed to cyproterone acetate in each group. | at the end of study, an average of 2 years | 
| Occurrence of hormonodependant cancer | Number of hormonodependant cancer occurrence the index case and in first-degree relatives in each group. | at the end of study, an average of 2 years | 
| Characteristic of the meningioma : Size, Localization, treatment, evolution of meningioma | In goups 1 and 3. Size and Localization of meningioma will be determined by RMI examination. | at baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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meningioma, predisposition, genetic