A Study to Confirm if Fezolinetant Helps Reduce Hot Flashes in Women With Breast Cancer Who Are Having Hormone Therapy
- Conditions
- Hot Flashes
- Interventions
- Registration Number
- NCT06440967
- Lead Sponsor
- Astellas Pharma Global Development, Inc.
- Brief Summary
One of the standard treatments for women with breast cancer is hormone therapy, but this treatment can cause hot flashes. Hormone replacement therapy, or HRT, is most often prescribed for hot flashes for women in menopause but cannot be given to women on hormone therapy for breast cancer. Fezolinetant, an alternative to HRT, treats hot flashes for women in menopause. As hot flashes happen in the same way for women on hormone therapy for breast cancer, fezolinetant could help these women. In this study, women on hormone therapy for breast cancer who have moderate to severe hot flashes will take part. They will either take fezolinetant or a placebo to treat their hot flashes. The placebo looks like fezolinetant but doesn't have any medicine in it.
The main aim of this study is to confirm if women who take fezolinetant have fewer hot flashes that are less severe compared to women who take the placebo.
Women 18 years or older seeking treatment for hot flashes. They can take part in the study if they have an average of 7 or more moderate to severe hot flashes each day. They are having hormone therapy for breast cancer from stage 0 (cancer cells that have not spread to nearby tissue) up to stage 3+ (the cancer has spread from the breast to the lymph nodes near the breast or the chest wall).
The women will be assigned 1 of 2 study treatments (fezolinetant or placebo) by chance alone. Treatment will be double-blinded. That means that the women in the study and the study doctors will not know who takes which of the study treatments (fezolinetant or placebo). Women who take part in the study will take 1 tablet every day for 52 weeks (1 year). Each woman will be given an electronic handheld device with an app to track their hot flashes on a daily basis. Some women may be able to use the app on their own smartphone. They will also use another device to answer questions about how hot flashes affect their daily life. During the study, the women will visit their study clinic about every 4 weeks for a health check. The last clinic visit will be 3 weeks after the women take their last tablet of study treatment (fezolinetant or placebo). After this visit the women will be called twice to check their health. The women will be in the study for about 2 years.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 540
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Participant has a personal history of stage 0-3 hormone receptor positive (HR+), either human epidermal growth factor receptor (HER)-2+ or HER-2- breast cancer; appropriate documentation includes a written or electronic report.
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Participant must be receiving stable maintenance adjuvant endocrine therapy (tamoxifen 20 mg daily or aromatase inhibitors, such as anastrozole, letrozole and exemestane) with or without gonadotropin-releasing hormone (GnRH) agonists/antagonists for a minimum of 4 months and be planning to continue on adjuvant endocrine therapy for the duration of the trial without change to therapy, brand or dose. Add-on therapies for breast cancer adjuvant treatment (e.g., cyclin dependent kinase-4 (CDK4) inhibitors) are allowed.
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Participant has a minimum average of 7 moderate to severe hot flashes (HFs) (vasomotor symptoms (VMS)) per day as recorded in the electronic daily diary (data must be available for at least 7 of the last 10 days prior to randomization).
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Has an European Cooperative Oncology Group (ECOG) score 0 or 1.
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Has at least 12-month life expectation.
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Participant is born female.
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Female participant: Is not pregnant and at least 1 of the following conditions apply:
- Not a woman of childbearing potential (WOCBP)
- WOCBP who has a negative urine or serum pregnancy test at screening and day 1 and agrees to follow the contraceptive guidance from the time of informed consent through at least 30 days after final investigational study intervention administration.
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Female participant: Must not be breastfeeding or lactating starting at screening and while the participant is taking investigational study intervention and for 30 days after final investigational study intervention administration.
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Female participant: Must not donate ova starting at first administration of study intervention and while the participant is taking investigational study intervention and for 30 days after final investigational study intervention administration.
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Participant agrees not to participate in another interventional study while participating in the present study until the end of the 1-year extension follow-up period.
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Participant's condition is stable as determined on the basis of medical history and general physical examination (including a bimanual clinical pelvic examination devoid of relevant clinical findings performed at the screening visit), hematology and biochemistry parameters, pulse rate and/or blood pressure and electrocardiogram (ECG) (or showing no clinically relevant deviations obtained within the last 3 months or at screening).
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Participant has no new clinically significant findings on breast examination or from imaging (mammogram or breast ultrasound). Results indicate that the participant is a good candidate for the study. Appropriate documentation includes a written or electronic report. In case of double mastectomy, imaging is not needed.
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Participant has a negative serology panel (including hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody and human immunodeficiency virus (HIV) antibody screens).
- Participant has diagnosis of metastatic breast cancer (stage 4).
- Participant has current or history (except complete remission for 5 years or more prior to signing informed consent) of any malignancy except for HR+ breast cancer (stage 0 to 3) or basal cell carcinoma.
- Participant has had surgery or non-surgical (chemotherapy or radiotherapy) treatment for breast cancer within the last 3 months prior to signing informed consent.
- Participant has active liver disease, jaundice, or elevated liver aminotransferases (alanine aminotransferase (ALT) or aspartate aminotransferase (AST)), elevated total bilirubin (TBL) or direct bilirubin (DBL), or elevated alkaline phosphatase (ALP) at screening. A participant with mildly elevated ALT or AST up to < 2 × upper limit of normal (ULN) can be enrolled if TBL and DBL are normal. Participant with mildly elevated ALP (up to < 1.5 × ULN) can be enrolled if cholestatic liver disease is excluded and no cause other than fatty liver is diagnosed. Participant with Gilbert's syndrome with elevated TBL may be enrolled as long as DBL, hemoglobin and reticulocytes are normal.
- Participant has creatinine > 1.5 x ULN; or estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula < 30 mL/min/1.73 m2 at the screening visit.
- Participant has a history of endometrial hyperplasia or uterine/endometrial cancer.
- Participant has a medical condition or chronic disease (including history of neurological [including cognitive], hepatic, renal, cardiovascular, gastrointestinal, pulmonary [e.g., moderate asthma], endocrine, or gynecological disease) or malignancy that could confound interpretation of the study outcome.
- Participant uses a prohibited therapy (menopause hormone therapy (MHT), estradiol-containing hormonal contraceptive progestin and progesterone-only medicines, any treatment for VMS [prescription medications, over-the-counter, or herbal] or CYP1A2 (cytochrome P450) inhibitors) or is not willing to wash out such drugs; in addition, medications that are contraindicated due to underlying breast cancer diagnosis and the adjuvant endocrine therapy.
- Participant has a known substance abuse or alcohol addiction within 6 months of screening.
- Participant has received any investigational therapy within 90 days or 5 half-lives, whichever is longer, prior to screening.
- Participant has any condition, which makes the participant unsuitable for study participation.
- Participant has a known or suspected hypersensitivity to fezolinetant, the adjuvant endocrine therapy being used, or any components of the formulations used.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Fezolinetant Fezolinetant Participants taking tamoxifen or an aromatase inhibitor will receive fezolinetant once daily for 52 weeks. After the end of the 52 week treatment period, participants will continue to participate in the extension follow up until week 104. They will continue to receive the adjuvant endocrine therapy as needed. Fezolinetant Tamoxifen Participants taking tamoxifen or an aromatase inhibitor will receive fezolinetant once daily for 52 weeks. After the end of the 52 week treatment period, participants will continue to participate in the extension follow up until week 104. They will continue to receive the adjuvant endocrine therapy as needed. Fezolinetant Aromatase inhibitor Participants taking tamoxifen or an aromatase inhibitor will receive fezolinetant once daily for 52 weeks. After the end of the 52 week treatment period, participants will continue to participate in the extension follow up until week 104. They will continue to receive the adjuvant endocrine therapy as needed. Placebo Placebo Participants taking tamoxifen or an aromatase inhibitor will receive matching placebo once daily for 52 weeks. After the end of the 52 week treatment period, participants will continue to participate in the extension follow up until week 104. They will continue to receive the adjuvant endocrine therapy as needed. Placebo Tamoxifen Participants taking tamoxifen or an aromatase inhibitor will receive matching placebo once daily for 52 weeks. After the end of the 52 week treatment period, participants will continue to participate in the extension follow up until week 104. They will continue to receive the adjuvant endocrine therapy as needed. Placebo Aromatase inhibitor Participants taking tamoxifen or an aromatase inhibitor will receive matching placebo once daily for 52 weeks. After the end of the 52 week treatment period, participants will continue to participate in the extension follow up until week 104. They will continue to receive the adjuvant endocrine therapy as needed.
- Primary Outcome Measures
Name Time Method Mean change from Baseline to Week 4 in the frequency of moderate to severe VMS Baseline to Week 4 Frequency of moderate and severe vasomotor symptoms (VMS) events will be calculated as the sum of moderate and severe VMS events per day.
Mean change from Baseline to Week 12 in the frequency of moderate to severe VMS Baseline to Week 12 Frequency of moderate and severe VMS events will be calculated as the sum of moderate and severe VMS events per day.
Mean change from Baseline to Week 4 in the severity of moderate to severe VMS Baseline to Week 4 The severity of VMS will be calculated using a weighted average of VMS events.
Mean change from Baseline to Week 12 in the severity of moderate to severe VMS Baseline to Week 12 The severity of VMS will be calculated using a weighted average of VMS events.
- Secondary Outcome Measures
Name Time Method PK of tamoxifen Metabolite endoxifen in Plasma: CL/F Up to Week 24 CL/F will be derived using a population PK model.
PK of tamoxifen Metabolite endoxifen in Plasma: Vc/F Up to Week 24 Vc/F will be derived using a population PK model.
PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: Cavg Up to Week 24 Cavg will be derived using a population PK model.
PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: Ctrough Up to Week 24 Ctrough will be derived using a population PK model.
Mean change from Baseline to Week 12 in the MENQOL VMS 1 week recall domain score Baseline to Week 12 The Menopause-specific Quality of Life Questionnaire (MENQOL) is a 29-item patient-reported outcome (PRO) measure that assesses the impact of 4 domains of menopausal symptoms, as experienced over the last week: vasomotor, psychosocial, physical and sexual. Each item score ranges from 1 to 8, and each domain is scored separately; each domain mean ranges from 1 to 8. The overall questionnaire score is the mean of the domain means. Higher scores represent more bothersome menopausal symptoms. A reduction (improvement) of 1 is the minimum clinically important difference in MENQoL.
Mean Change from Baseline to Week 12 in the PROMIS SD SF 8b Total (raw) Score Baseline to Week 12 The Patient-reported Outcomes Measurement Information System Sleep Disturbance - Short Form 8b (PROMIS SD SF 8b) assesses self-reported sleep disturbance over the past 7 days and includes perceptions of: restless sleep; satisfaction with sleep; refreshing sleep; difficulties sleeping, getting to sleep or staying asleep; amount of sleep; and sleep quality. Responses to each of the 8 items range from 1 to 5 and the range of possible summed raw scores is 8 to 40. Higher scores on the PROMIS SD SF 8b indicate more of the concept measured (disturbed sleep).
Mean change from Baseline to Week 24 in the frequency of moderate to severe VMS Baseline to Week 24 Frequency of moderate and severe VMS events will be calculated as the sum of moderate and severe VMS events per day.
Mean Change from Baseline to Week 24 in the severity of moderate to severe VMS Baseline to Week 24 The severity of VMS will be calculated using a weighted average of VMS events.
Number of participants with Treatment Emergent Adverse Events (TEAEs) Up to Week 55 A TEAE is defined as Adverse Event (AE) observed after starting administration of the investigational study intervention and up to 21 days after the last dose of investigational study intervention.
Number of participants with Adverse Events of Special Interest (AESIs) Up to Week 55 AEs of special interest in this study will include: Progression of breast cancer including metastasis; Adverse events of uterine bleeding; Adverse events of liver test elevations; Any liver AE leading to discontinuation.
Number of participants with laboratory value abnormalities and/or adverse events (AEs) Up to Week 55 Number of participants with potentially clinically significant laboratory values.
Number of participants with vital sign abnormalities and/or adverse events (AEs) Up to Week 55 Number of participants with potentially clinically significant vital sign values.
Number of participants with electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs) Up to Week 52 Number of participants with potentially clinically significant ECG values.
Mean change from Baseline in the frequency of moderate to severe VMS to the average frequency of moderate to severe VMS over Weeks 1 to 3 Baseline and Weeks 1 to 3 Frequency of moderate and severe VMS events will be calculated as the sum of moderate and severe VMS events per day.
Mean Change from Baseline in the frequency of moderate to severe VMS to the average frequency of moderate to severe VMS over Weeks 5 to 11 Baseline and Weeks 5 to 11 Frequency of moderate and severe VMS events will be calculated as the sum of moderate and severe VMS events per day.
Mean change from Baseline in the severity of moderate to severe VMS to the average severity of moderate to severe VMS over weeks 1 to 3 Baseline and Weeks 1 to 3 The severity of VMS will be calculated using a weighted average of VMS events.
Mean Change from Baseline in the severity of moderate to severe VMS to the average severity of moderate to severe VMS over weeks 5 to 11 Baseline and Weeks 5 to 11 The severity of VMS will be calculated using a weighted average of VMS events.
Percent reduction >/= 50% in the frequency of moderate and severe VMS from baseline Baseline to Weeks 1, 4, 8 and 12 Frequency of moderate and severe VMS events will be calculated as the sum of moderate and severe VMS events per day. Percent reduction of \>/= 50% will be reported.
Percent reduction >/= 75% in the frequency of moderate and severe VMS from baseline Baseline to Weeks 1, 4, 8 and 12 Frequency of moderate and severe VMS events will be calculated as the sum of moderate and severe VMS events per day. Percent reduction of \>/= 75% will be reported.
Percent reduction at 100% in the frequency of moderate and severe VMS from baseline Baseline to Weeks 1, 4, 8 and 12 Frequency of moderate and severe VMS events will be calculated as the sum of moderate and severe VMS events per day. Percent reduction of 100% will be reported.
Pharmacokinetics (PK) of Fezolinetant in Plasma: Apparent Clearance (CL/F) for participants taking tamoxifen Up to Week 24 CL/F will be derived using a population PK model.
Pharmacokinetics (PK) of Fezolinetant in Plasma: Apparent Clearance (CL/F) for participants taking aromatase inhibitors Up to Week 24 CL/F will be derived using a population PK model.
PK of Fezolinetant in Plasma: apparent volume of distribution (Vc/F) for participants taking tamoxifen Up to Week 24 Vc/F will be derived using a population PK model.
PK of Fezolinetant in Plasma: apparent volume of distribution (Vc/F) for participants taking aromatase inhibitors Up to Week 24 Vc/F will be derived using a population PK model.
PK of Fezolinetant in Plasma: average concentration (Cavg) for participants taking tamoxifen Up to Week 24 Cavg will be derived using a population PK model.
PK of Fezolinetant in Plasma: Cavg for participants taking aromatase inhibitors Up to Week 24 Cavg will be derived using a population PK model.
PK of Fezolinetant in Plasma: trough concentration (Ctrough) for participants taking tamoxifen Up to Week 24 Ctrough will be derived using a population PK model.
PK of Fezolinetant in Plasma: Ctrough for participants taking aromatase inhibitors Up to Week 24 Ctrough will be derived using a population PK model.
PK of tamoxifen in Plasma: CL/F Up to Week 24 CL/F will be derived using a population PK model.
PK of tamoxifen in Plasma: Vc/F Up to Week 24 Vc/F will be derived using a population PK model.
PK of tamoxifen in Plasma: Cavg Up to Week 24 Cavg will be derived using a population PK model.
PK of tamoxifen in Plasma: Ctrough Up to Week 24 Ctrough will be derived using a population PK model.
PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: CL/F Up to Week 24 CL/F will be derived using a population PK model.
PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: Vc/F Up to Week 24 Vc/F will be derived using a population PK model.
PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: Cavg Up to Week 24 Cavg will be derived using a population PK model.
PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: Ctrough Up to Week 24 Ctrough will be derived using a population PK model.
PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: CL/F Up to Week 24 CL/F will be derived using a population PK model.
PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: Vc/F Up to Week 24 Vc/F will be derived using a population PK model.
PK of tamoxifen Metabolite endoxifen in Plasma: Cavg Up to Week 24 Cavg will be derived using a population PK model.
PK of tamoxifen Metabolite endoxifen in Plasma: Ctrough Up to Week 24 Ctrough will be derived using a population PK model.
PK of aromatase inhibitors in Plasma: CL/F Up to Week 24 CL/F will be derived using a population PK model.
PK of aromatase inhibitors in Plasma: Vc/F Up to Week 24 Vc/F will be derived using a population PK model.
PK of aromatase inhibitors in Plasma: Cavg Up to Week 24 Cavg will be derived using a population PK model.
PK of aromatase inhibitors in Plasma: Ctrough Up to Week 24 Ctrough will be derived using a population PK model.
Mean change from Baseline in the MENQOL Total Score Baseline to Weeks 4, 8, 12 and 24 The MENQOL is a 29-item PRO measure that assesses the impact of 4 domains of menopausal symptoms, as experienced over the last week: vasomotor, psychosocial, physical and sexual. The total score is the mean of the domain means. Higher scores represent more bothersome menopausal symptoms. A reduction (improvement) of 1 is the minimum clinically important difference for the MENQoL.
Mean change from Baseline in the MENQOL VMS 1-week recall domain score Baseline to Weeks 4, 8 and 24 The MENQOL is a 29-item PRO measure that assesses the impact of 4 domains of menopausal symptoms, as experienced over the last week: vasomotor, psychosocial, physical and sexual. Each item score ranges from 1 to 8, and each domain is scored separately; each domain mean ranges from 1 to 8. Higher scores represent more bothersome menopausal symptoms.
Mean change from Baseline in the MENQOL psychosocial 1-week recall domain score Baseline to Weeks 4, 8, 12 and 24 The MENQOL is a 29-item PRO measure that assesses the impact of 4 domains of menopausal symptoms, as experienced over the last week: vasomotor, psychosocial, physical and sexual. Each item score ranges from 1 to 8, and each domain is scored separately; each domain mean ranges from 1 to 8. Higher scores represent more bothersome menopausal symptoms.
Mean change from Baseline in the MENQOL physical 1-week recall domain score Baseline to Weeks 4, 8, 12 and 24 The MENQOL is a 29-item PRO measure that assesses the impact of 4 domains of menopausal symptoms, as experienced over the last week: vasomotor, psychosocial, physical and sexual. Each item score ranges from 1 to 8, and each domain is scored separately; each domain mean ranges from 1 to 8. Higher scores represent more bothersome menopausal symptoms.
Mean change from Baseline in the MENQOL sexual 1-week recall domain score Baseline to Weeks 4, 8, 12 and 24 The MENQOL is a 29-item PRO measure that assesses the impact of 4 domains of menopausal symptoms, as experienced over the last week: vasomotor, psychosocial, physical and sexual. Each item score ranges from 1 to 8, and each domain is scored separately; each domain mean ranges from 1 to 8. Higher scores represent more bothersome menopausal symptoms.
Mean change from Baseline in the PROMIS SD SF 8b Total (raw) Score Baseline to Weeks 4, 8 and 24 The PROMIS SD SF 8b assesses self reported sleep disturbance over the past 7 days and includes perceptions of: restless sleep; satisfaction with sleep; refreshing sleep; difficulties sleeping, getting to sleep or staying asleep; amount of sleep; and sleep quality. Responses to each of the 8 items range from 1 to 5 and the range of possible summed raw scores is 8 to 40. Higher scores on the PROMIS SD SF 8b indicate more of the concept measured (disturbed sleep).
Scores on the Patient Global Impression of Change (PGI-C) VMS Up to Week 24 The PGI-C VMS evaluates patient perceived change in hot flashes/night sweats from the initiation of treatment. Ratings range from (1) much better to (7) much worse.
Change from Baseline in the Patient Global Impression of Severity (PGI-S) VMS Score Baseline to Weeks 4, 8, 12 and 24 The PGI-S VMS evaluates patient perceived severity of hot flashes/night sweats. Ratings range from (1) no problems to (4) severe problems.
Scores on the PGI-C sleep disturbance (SD) Up to Week 24 PGI-C SD evaluates patient perceived change in sleep disturbance from the initiation of treatment. Ratings range from (1) much better to (7) much worse.
Change from Baseline in the PGI-S SD Score Baseline to Weeks 4, 8, 12 and 24 The PGI-S SD evaluates patient perceived severity of sleep disturbance. Ratings range from (1) no problems to (4) severe problems.
PGI-S SD response Up to Week 24 Proportion of patients achieving a response in PGI-S SD. The PGI-S SD evaluates patient perceived severity of sleep disturbance. Ratings range from (1) no problems to (4) severe problems. PGI-S SD response is defined as at least 2 levels of improvement on PGI-S SD from baseline. Non-response is defined as not achieving a response.
Trial Locations
- Locations (66)
Site FR33002
🇫🇷Saint Herblain Cedex, France
Site DE49001
🇩🇪Bottrop, Germany
Site DE49009
🇩🇪Leipzig, Germany
Site DE49007
🇩🇪Moenchengladbach, Germany
Site HU36008
🇭🇺Budapest, Hungary
Site DE45003
🇩🇰Esbjerg, Denmark
Site FR33003
🇫🇷Angers Cedex 9, France
Site FR33005
🇫🇷Bordeaux Cedex, France
Site FR33013
🇫🇷Le Mans, France
Site HU36006
🇭🇺Debrecen, Hungary
Site IT39012
🇮🇹Terni, Italy
Site HU36002
🇭🇺Kecskemet, Hungary
Site HU36010
🇭🇺Salgotarjan, Hungary
Site HU36003
🇭🇺Szekesfehervar, Hungary
Site NL31010
🇳🇱Breda, Netherlands
Site NL31006
🇳🇱Dirksland, Netherlands
Site NL31004
🇳🇱Rotterdam, Netherlands
Site NL31009
🇳🇱Terneuzen, Netherlands
Site PO48005
🇵🇱Bialystok, Poland
Site PO48004
🇵🇱Katowice, Poland
Site PO48017
🇵🇱Katowice, Poland
Site PO48015
🇵🇱Krakow, Poland
Site PO48007
🇵🇱Lodz, Poland
Site PO48020
🇵🇱Pila, Poland
Site PO48002
🇵🇱Poznan, Poland
Site PO48018
🇵🇱Poznan, Poland
Site PO48003
🇵🇱Swidnik, Poland
Site PO48010
🇵🇱Szczecin, Poland
Site PO48001
🇵🇱Warszawa, Poland
Site ES34011
🇪🇸Barcelona, Spain
Site ES34020
🇪🇸Barcelona, Spain
Site ES34010
🇪🇸Elche, Spain
Site ES34005
🇪🇸Granada, Spain
Site ES34006
🇪🇸Jaen, Spain
Site ES34017
🇪🇸Leon, Spain
Site ES34007
🇪🇸Madrid, Spain
Site ES34022
🇪🇸Madrid, Spain
Site ES34015
🇪🇸Majadahonda, Spain
Site ES34002
🇪🇸Murcia, Spain
Site ES34014
🇪🇸Murcia, Spain
Site ES34009
🇪🇸Sevilla, Spain
Site CZ42003
🇨🇿Horovice, Czechia
Site FR33007
🇫🇷Lille Cedex, France
Site IT39003
🇮🇹Milano, Italy
Site NL31001
🇳🇱Haarlem, Netherlands
Site NL31012
🇳🇱Rotterdam, Netherlands
Site CZ42007
🇨🇿Vodnany, Czechia
Site DK45007
🇩🇰Aalborg, Denmark
Site GB44006
🇬🇧Glasgow, United Kingdom
Site GB44002
🇬🇧Liverpool, United Kingdom
Site GB44005
🇬🇧London, United Kingdom
Site CA15002
🇨🇦Montreal, Quebec, Canada
Site CA15001
🇨🇦Quebec City, Quebec, Canada
Site CA15003
🇨🇦Sherbrooke, Quebec, Canada
Site CA15007
🇨🇦Trois-Rivières, Canada
Site CZ42006
🇨🇿Ceske Budejovice, Czechia
Site CZ42011
🇨🇿Novy Jicin, Czechia
Site CZ42001
🇨🇿Olomouc, Czechia
Site CZ42004
🇨🇿Tabor, Czechia
Site CZ42009
🇨🇿Vsetin, Czechia
Site DE45008
🇩🇰Sonderborg, Denmark
Site FR33001
🇫🇷Bayonne, France
Site FR33012
🇫🇷Lyon Cedex 08, France
Site FR33008
🇫🇷Montpellier, France
Site PO48006
🇵🇱Bydgoszcz, Poland
Site ES34003
🇪🇸Girona, Spain