New pill combo aims to outsmart resistant breast cancer

NCT ID NCT04964934

Disease control Sponsor: AstraZeneca Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Jul 15, 2026 · Updated 2 times

Summary

This phase 3 trial tests whether switching to a new oral drug (AZD9833) plus a CDK4/6 inhibitor can delay cancer progression better than staying on standard aromatase inhibitor therapy in people with HR+/HER2- metastatic breast cancer who have an ESR1 mutation. About 315 participants whose cancer has not yet worsened on initial treatment are being randomly assigned to either switch or continue their current regimen. The main goal is to see how long the cancer stays under control.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: AZD9833 (a next-generation oral SERD drug) combined with a CDK4/6 inhibitor (palbociclib, abemaciclib, or ribociclib)
What this could lead to: If successful, this could offer a new oral treatment option for people with a specific type of advanced breast cancer, potentially delaying disease progression longer than current standard therapy.
What could go wrong: This is an early-switch strategy in a specific genetic subgroup, so results may not apply to all patients. The trial is still ongoing, and the new drug may not prove superior or could have unexpected side effects.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 3

Large-scale testing in a bigger group. Usually the last step before a treatment can be approved.

Participants

315 people

The number who actually took part.

Started

Jun 2021

Expected to finish

Sep 2028

An estimate. End dates often move.

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 to 130 years

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

INCLUSION CRITERIA: INFORMATION FOR TRIAL PARTICIPANTS - Participants can join the trial if they: * Have advanced breast cancer that is not able to be treated with surgery or radiation; * Have an ESR1 mutation in their cancer; * Have breast cancer that is HR-positive and HER2-negative; * Are currently being treated with a CDK4/6 inhibitor and an AI and have been taking these drugs for at least 6 months; * Have not had their cancer get worse after taking an AI and CDK4/6 inhibitor; * Are able to do their daily activities; * Are at least 18. Full list of inclusion criteria: * Proven diagnosis of adenocarcinoma of the breast with evidence of locoregionally recurrent or metastatic disease not amenable to resection or radiation therapy with curative intent; * Documentation of histologically confirmed diagnosis of estrogen receptor positive (ER+) /HER2- breast cancer based on local laboratory results; * Currently on AI (letrozole or anastrozole) + CDK4/6 inhibitor (palbociclib, abemaciclib or ribociclib) ± LHRH as the initial endocrine based treatment for advanced disease; * Eastern Cooperative Oncology Group performance status of 0 or 1; * ESR1m detected by central testing of ctDNA with Guardant360® CDx; * Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures; * Adequate organ and marrow function. EXCLUSION CRITERIA: INFORMATION FOR TRIAL PARTICIPANTS - Participants cannot join the trial if they: * Had certain types of tumors in the past that may come back; * Are currently taking any other treatments for their cancer or other conditions including hormone replacements, medications, or supplements that could interfere with the trial treatment; * Have or have had any major health problem, infection, or recent surgery that could make it difficult or dangerous to participate in this trial. Full list of exclusion criteria: * Advanced, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term; * Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease; * Any evidence of severe or uncontrolled systemic diseases which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol; * Patient with known or family history of severe heart disease; * Previous treatment with AZD9833, investigational SERDs or fulvestrant; * Currently pregnant (confirmed with positive pregnancy test) or breastfeeding; * Persistent non-haematological toxicities (CTCAE Grade \> 2) caused by CDK4/6 inhibitor and/or AI treatment.

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Conditions

The condition(s) this trial relates to.

breast disorder breast neoplasm hormone receptor-positive breast cancer neoplasm Neoplasm Metastasis Neoplasms by Site

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

ER-positive HER2-negative breast cancer

Contacts and locations

Locations

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Phoenix, Arizona, 85054, United States
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Hot Springs, Arkansas, 71913, United States
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Little Rock, Arkansas, 72205, United States
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Long Beach, California, 90806, United States
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San Diego, California, 92123, United States
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Santa Rosa, California, 92805, United States
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Grand Junction, Colorado, 81501, United States
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Lone Tree, Colorado, 80124, United States
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Fort Myers, Florida, 33901, United States
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Jacksonville, Florida, 32224, United States
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Jacksonville, Florida, 32256, United States
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St. Petersburg, Florida, 33705, United States
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Atlanta, Georgia, 30318, United States
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Atlanta, Georgia, 30322, United States
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Atlanta, Georgia, 30342, United States
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Park Ridge, Illinois, 60068, United States
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Fort Wayne, Indiana, 46804, United States
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Indianapolis, Indiana, 46250, United States
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Baltimore, Maryland, 21202, United States
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Boston, Massachusetts, 02215, United States
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Fairhaven, Massachusetts, 02719, United States
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Foxborough, Massachusetts, 02035, United States
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Milford, Massachusetts, 01757, United States
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South Weymouth, Massachusetts, 02190, United States
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Detroit, Michigan, 48202, United States
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Grand Rapids, Michigan, 49503, United States
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Rochester, Minnesota, 55905, United States
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Oxford, Mississippi, 38655, United States
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Kansas City, Missouri, 64111, United States
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St Louis, Missouri, 63110, United States
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Billings, Montana, 59101, United States
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Omaha, Nebraska, 68130, United States
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Camden, New Jersey, 08103, United States
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Ridgewood, New Jersey, 07450, United States
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Brooklyn, New York, 11215, United States
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East Syracuse, New York, 13057, United States
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New Hyde Park, New York, 11042, United States
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New York, New York, 10065, United States
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New York, New York, 11355, United States
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Shirley, New York, 11967, United States
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Goldsboro, North Carolina, 27534, United States
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Canton, Ohio, 44710, United States
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Cincinnati, Ohio, 45220, United States
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Columbus, Ohio, 43219, United States
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Portland, Oregon, 97213, United States
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Philadelphia, Pennsylvania, 19104, United States
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Pittsburgh, Pennsylvania, 15213, United States
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York, Pennsylvania, 17403, United States
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Greenville, South Carolina, 29607, United States
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West Columbia, South Carolina, 29169, United States
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Knoxville, Tennessee, 37916, United States
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Memphis, Tennessee, 38120, United States
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Nashville, Tennessee, 37203, United States
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Bedford, Texas, 76022, United States
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Dallas, Texas, 75246, United States
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Houston, Texas, 77024, United States
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Houston, Texas, 77030, United States
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Longview, Texas, 75601, United States
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San Antonio, Texas, 78240, United States
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Salt Lake City, Utah, 84106, United States
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Midlothian, Virginia, 23114, United States
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Norfolk, Virginia, 23502, United States
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Tacoma, Washington, 98405, United States
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Waukesha, Wisconsin, 53226, United States
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Birtinya, 4575, Australia
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Darlinghurst, 2010, Australia
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Graz, 8036, Austria
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Innsbruck, 6020, Austria
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Salzburg, 5020, Austria
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Vienna, 1130, Austria
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Leuven, 3000, Belgium
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Liège, 4000, Belgium
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Namur, 5000, Belgium
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Haskovo, 6300, Bulgaria
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Panagyurishte, 4500, Bulgaria
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Pleven, 5804, Bulgaria
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Plovdiv, 4004, Bulgaria
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Sofia, 1303, Bulgaria
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Sofia, 1330, Bulgaria
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Sofia, 1407, Bulgaria
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Sofia, 1431, Bulgaria
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Sofia, 1527, Bulgaria
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Calgary, Alberta, T2N 5G2, Canada
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Vancouver, British Columbia, V5Z 4E6, Canada
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Ottawa, Ontario, K1H 8L6, Canada
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Lévis, Quebec, G6V 3Z1, Canada
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Montreal, Quebec, H1T 2M4, Canada
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Montreal, Quebec, H2X 0C1, Canada
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Montreal, Quebec, H3T 1E2, Canada
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Québec, Quebec, G1S 4L8, Canada
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Avignon, 84918, France
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Brest, 29200, France
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Clermont-Ferrand, 63050, France
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Dijon, 21079, France
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Limoges, 83000, France
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Lorient, 56322, France
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Lyon, 69373, France
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Marseille, 13273, France
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Metz-Tessy, 74370, France
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Nîmes, 30029, France
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Paris, 75248, France
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Rouen, 76021, France
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Saint-Cloud, 92210, France
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Saint-Herblain, 44805, France
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Toulouse, 31100, France
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Tours, 37000, France
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Vandœuvre-lès-Nancy, 54519, France
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Vantoux, 57070, France
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Villejuif, 94805, France
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Ansbach, 91522, Germany
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Augsburg, 86156, Germany
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Bonn, 53111, Germany
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Chemnitz, 09116, Germany
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Dresden, 01307, Germany
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Erlangen, 91054, Germany
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Essen, 45130, Germany
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Freiburg im Breisgau, 79110, Germany
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Hösbach, 63768, Germany
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Immenstadt im Allgäu, 87509, Germany
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Koblenz, 56068, Germany
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Leipzig, 4103, Germany
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Mannheim, 68167, Germany
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München, 80634, Germany
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Paderborn, 33098, Germany
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Ratingen, 40878, Germany
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Ravensburg, 88212, Germany
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Regensburg, 93053, Germany
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Stade, 21680, Germany
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Tübingen, 72076, Germany
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Ulm, 89075, Germany
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Budapest, 1062, Hungary
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Budapest, 1122, Hungary
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Miskolc, 3526, Hungary
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Szekszárd, 7100, Hungary
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Szolnok, 5000, Hungary
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Zalaegerszeg, 8900, Hungary
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Beersheba, 8410101, Israel
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Haifa, 3109601, Israel
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Jerusalem, 91120, Israel
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Petah Tikva, 494142, Israel
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Ramat Gan, 5262000, Israel
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Bergamo, 24127, Italy
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Bologna, 40138, Italy
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Florence, 50134, Italy
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Meldola, 47014, Italy
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Milan, 20132, Italy
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Milan, 20141, Italy
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Misterbianco, 95045, Italy
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Naples, 80131, Italy
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Padova, 35128, Italy
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Roma, 00168, Italy
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Rozzano, 20089, Italy
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Chiba, 260-8717, Japan
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Chūōku, 104-0045, Japan
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Hidaka-shi, 350-1298, Japan
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Hirakata-shi, 573-1191, Japan
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Kitaadachi-gun, 362-0806, Japan
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Kōtoku, 135-8550, Japan
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Kumamoto, 860-8556, Japan
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Matsuyama, 791-0280, Japan
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Nagoya, 464-8681, Japan
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Nagoya, 467-8602, Japan
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Niigata, 951-8566, Japan
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Osaka, 540-0006, Japan
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Osaka, 541-8567, Japan
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Ota-shi, 373-8550, Japan
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Sapporo, 003-0804, Japan
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Shinagawa-ku, 142-8666, Japan
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Shinjuku-ku, 162-8655, Japan
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Takasaki-shi, 370-0829, Japan
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Takatsuki-shi, 569-8686, Japan
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Tsukuba, 305-8577, Japan
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Yokohama, 241-8515, Japan
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Drammen, 3004, Norway
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Oslo, 0450, Norway
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Bydgoszcz, 85-796, Poland
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Gdynia, 81-519, Poland
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Koszalin, 75-581, Poland
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Lodz, 90-302, Poland
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Poznan, 60-693, Poland
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Rzeszów, 35-001, Poland
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Tomaszów Mazowiecki, 97-200, Poland
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Warsaw, 02-781, Poland
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Guimarães, 4835-044, Portugal
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Lisbon, 1400-038, Portugal
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Lisbon, 1449-005, Portugal
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Lisbon, 1500-650, Portugal
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Lisbon, 1649-035, Portugal
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Loures, 2674-514, Portugal
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Porto, 4099-001, Portugal
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Porto, 4200-072, Portugal
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Porto, 4200-319, Portugal
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Vila Nova de Gaia, 4434-502, Portugal
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Moscow, 111123, Russia
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Moscow, 129090, Russia
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Moscow, 143423, Russia
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Nizhny Novgorod, 603126, Russia
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Podolsk, 142100, Russia
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Saint Petersburg, 194017, Russia
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Saint Petersburg, 197758, Russia
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Banská Bystrica, 974 01, Slovakia
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Bratislava, 833 01, Slovakia
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Košice, 041 91, Slovakia
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Michalovce, 07101, Slovakia
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Partizánske, 958 01, Slovakia
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Cheonan-si, 31151, South Korea
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Daegu, 42415, South Korea
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Goyang-si, 10408, South Korea
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Seongnam-si, 13620, South Korea
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Seongnam-si, 463-712, South Korea
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Seoul, 02841, South Korea
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Seoul, 03080, South Korea
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Seoul, 03722, South Korea
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Seoul, 05505, South Korea
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Seoul, 06273, South Korea
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Seoul, 06351, South Korea
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Seoul, 06591, South Korea
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A Coruña, 15009, Spain
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Badalona, 08003, Spain
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Barcelona, 8035, Spain
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L'Hospitalet de Llobregat, 08908, Spain
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Madrid, 28040, Spain
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Madrid, 28041, Spain
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Málaga, 29010, Spain
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Murcia, 30008, Spain
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Sant Joan Despí, 08970, Spain
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Seville, 41013, Spain
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Valencia, 46010, Spain
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Bern, CH-3010, Switzerland
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Chur, CH-7000, Switzerland
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Winterthur, 8401, Switzerland
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Kaohsiung City, 833, Taiwan
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Taichung, 40705, Taiwan
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Tainan, 70403, Taiwan
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Tainan, 710, Taiwan
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Taipei, 100, Taiwan
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Taipei, 110, Taiwan
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Taipei, 11259, Taiwan
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Taipei, 11490, Taiwan
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Taipei, 23561, Taiwan
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Taipei, Taiwan
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Taoyuan, 333, Taiwan
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Adana, 01120, Turkey (Türkiye)
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Ankara, 06010, Turkey (Türkiye)
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Ankara, 06100, Turkey (Türkiye)
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Ankara, 06340, Turkey (Türkiye)
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Ankara, 06520, Turkey (Türkiye)
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Cordaleo, 35575, Turkey (Türkiye)
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Izmir, 35100, Turkey (Türkiye)
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Izmir, 35360, Turkey (Türkiye)
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Kadıkoy/Istanbul, 34722, Turkey (Türkiye)
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Kayseri, 38039, Turkey (Türkiye)
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Blackpool, FY3 8NR, United Kingdom
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Cambridge, CB2 0QQ, United Kingdom
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London, SW3 6JJ, United Kingdom
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London, WC1N 3BG, United Kingdom
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Manchester, M20 4BX, United Kingdom
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Newport, NP10 8FZ, United Kingdom
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Nottingham, NG5 1PB, United Kingdom
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Portsmouth, PO6 3LY, United Kingdom
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Reading, RG2 9LH, United Kingdom
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Sheffield, S10 2SJ, United Kingdom
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Sutton, SM2 5PT, United Kingdom
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Taunton, TA1 5DA, United Kingdom

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