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

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.

Study Overview

• Status: Recruiting
• Conditions: Meningioma
• Intervention / Treatment: Procedure: oral smears

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 2000

Contacts and Locations

• Study Contact: Name: Marie-Laure RAFFIN-SANSON, MD, PhD; Phone Number: +33 1 49 09 54 95; Email: marie-laure.raffin-sanson@aphp.fr
• Study Contact Backup: Name: Marc SANSON, MD, PhD; Phone Number: +33 1 42 16 04 35; Email: marc.sanson@aphp.fr

Study Locations

• France
  • Boulogne-Billancourt, France, 92100
    • Recruiting
    • Endocrinology Nutrition Department, Ambroise Paré Hospital, APHP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adult women with or without meningioma either exposed or not to cyproterone acetate.

Description

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).

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
group 1: Exposed to CPA + Meningioma; 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; oral smears
group 2: Exposed to CPA without Meningioma; 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; oral smears
group 3: Not exposed to CPA, Meningioma diagnosed; 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; Subjects (women) never diagnosed with meningioma and not exposed to cyproterone acetate.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Marie-Laure RAFFIN-SANSON, MD, PhD, Service Endocrinologie Nutrition, Hôpital Ambroise Paré, APHP & EA4340, UFR Santé Simone Veil, Université Paris Saclay; Study Chair: Marc SANSON, MD, PhD, Equipe Génétique et Développement des Tumeurs Cérébrales, Service Neuro Oncologie, Hôpital Pitié Salpetrière, APHP

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2021
• Primary Completion (Estimated): April 19, 2025
• Study Completion (Estimated): April 19, 2025

Study Registration Dates

• First Submitted: April 30, 2020
• First Submitted That Met QC Criteria: April 30, 2020
• First Posted (Actual): May 1, 2020

Study Record Updates

• Last Update Posted (Actual): October 30, 2023
• Last Update Submitted That Met QC Criteria: October 27, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: genetic; meningioma; predisposition
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Meningioma
• Other Study ID Numbers: APHP200222; 2020-A00045-34 (Registry Identifier: IDRCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No