Study of Durvalumab Given With Chemotherapy, Durvalumab in Combination With Tremelimumab Given With Chemotherapy, or Chemotherapy in Patients With Unresectable Urothelial Cancer

NCT ID: NCT03682068

Last Updated: 2025-10-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

1246 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-09-27

Study Completion Date

2026-04-29

Brief Summary

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This is a randomized, open-label, controlled, multi-center, global Phase III study to determine the efficacy and safety of combining durvalumab ± tremelimumab with standard of care (SoC) chemotherapy (cisplatin + gemcitabine or carboplatin + gemcitabine doublet) followed by durvalumab monotherapy versus SoC alone as first-line chemotherapy in patients with histologically or cytologically documented, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra).

Detailed Description

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Conditions

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Unresectable Locally Advanced Urothelial Cancer Metastatic Urothelial Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Durvalumab in Combination with SoC Chemotherapy

Durvalumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks.

All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles:

* cisplatin+ gemcitabine
* If the patient is cisplatin-ineligible, carboplatin + gemcitabine

Group Type EXPERIMENTAL

Durvalumab

Intervention Type DRUG

Durvalumab IV (intravenous infusion)

Cisplatin + Gemcitabine

Intervention Type DRUG

Cisplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.

Carboplatin + Gemcitabine

Intervention Type DRUG

Carboplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.

Durvalumab in Combination with Tremelimumab+SoC Chemotherapy

Durvalumab and Tremelimumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks

Tremelimumab will be provided for 4 cycles.

All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles:

* cisplatin+ gemcitabine
* If the patient is cisplatin-ineligible, carboplatin + gemcitabine

Group Type EXPERIMENTAL

Durvalumab

Intervention Type DRUG

Durvalumab IV (intravenous infusion)

Tremelimumab

Intervention Type DRUG

Tremelimumab IV (intravenous infusion)

Cisplatin + Gemcitabine

Intervention Type DRUG

Cisplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.

Carboplatin + Gemcitabine

Intervention Type DRUG

Carboplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.

SoC Chemotherapy

Patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles:

* cisplatin+ gemcitabine
* If the patient is cisplatin-ineligible, carboplatin + gemcitabine

Group Type ACTIVE_COMPARATOR

Cisplatin + Gemcitabine

Intervention Type DRUG

Cisplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.

Carboplatin + Gemcitabine

Intervention Type DRUG

Carboplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.

Interventions

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Durvalumab

Durvalumab IV (intravenous infusion)

Intervention Type DRUG

Tremelimumab

Tremelimumab IV (intravenous infusion)

Intervention Type DRUG

Cisplatin + Gemcitabine

Cisplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.

Intervention Type DRUG

Carboplatin + Gemcitabine

Carboplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.

Intervention Type DRUG

Other Intervention Names

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MEDI4736

Eligibility Criteria

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Inclusion Criteria

* Patients with histologically or cytologically documented, unresectable, locally advanced or metastatic transitional cell carcinoma (transitional cell and mixed transitional/non-transitional cell histologies) of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra)
* Patients who have not been previously treated with first-line chemotherapy. Patients who have received prior definitive chemoradiation, adjuvant or neoadjuvant treatment for locally advanced disease are eligible provided that progression to locally advanced or metastatic disease has occurred \>12 months from the last therapy \[for chemoradiation and adjuvant treatment\] or \>12 months from the last surgery \[for neoadjuvant treatment\].
* At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion at baseline.
* World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrolment
* Adequate organ and marrow function as defined in the protocol
* Life expectancy ≥12 weeks in the opinion of the investigator
* Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients.

Exclusion Criteria

* Prior exposure to immune-mediated therapy (with exclusion of Bacillus Calmette Guerin), including but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD L1, or anti-PD-L2 antibodies, except therapeutic anticancer vaccines, which are permitted. Prior local intervesical chemotherapy or immunotherapy is allowed if completed at least 28 days prior to the initiation of study treatment.
* No severe concomitant condition that requires immunosuppression medication
* Untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
* Patients who may be eligible for or are being considered for radical resection during the course of the study.
* Any medical contraindications to platinum (cisplatin or carboplatin) based doublet chemotherapy and/or known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Arezzo, , Italy

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Milan, , Italy

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Milan, , Italy

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Napoli, , Italy

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Orbassano, , Italy

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Parma, , Italy

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Pavia, , Italy

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Roma, , Italy

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Terni, , Italy

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Verona, , Italy

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Bunkyō City, , Japan

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Chūōku, , Japan

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Fukuoka, , Japan

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Hirosaki-shi, , Japan

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Kanazawa, , Japan

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Kita-gun, , Japan

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Koshigaya-shi, , Japan

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Kōtoku, , Japan

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Kumamoto, , Japan

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Kumamoto, , Japan

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Kyoto, , Japan

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Miyazaki, , Japan

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Nagasaki, , Japan

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Nagoya, , Japan

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Nagoya, , Japan

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Niigata, , Japan

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Osaka, , Japan

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Osaka, , Japan

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Osakasayama-shi, , Japan

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Shinjuku-ku, , Japan

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Suita-shi, , Japan

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Toyama, , Japan

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Yokohama, , Japan

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Yokohama, , Japan

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Bacolod, , Philippines

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Baguio City, , Philippines

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Cebu, , Philippines

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Davao City, , Philippines

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Makati, , Philippines

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Manila, , Philippines

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Quezon City, , Philippines

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Quezon City, , Philippines

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Bialystok, , Poland

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Gdansk, , Poland

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Grudziądz, , Poland

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Koszalin, , Poland

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Krakow, , Poland

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Olsztyn, , Poland

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Poznan, , Poland

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Radom, , Poland

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Warsaw, , Poland

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Ivanovo, , Russia

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Krasnoyarsk, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Nizhny Novgorod, , Russia

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Nizhny Novgorod, , Russia

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Omsk, , Russia

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Rostov-on-Don, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Tyumen, , Russia

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Vologda, , Russia

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Goyang-si, , South Korea

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Incheon, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Suwon, , South Korea

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Barcelona, , Spain

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taoyuan District, , Taiwan

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Bangkok, , Thailand

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Bangkok, , Thailand

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Khon Kaen, , Thailand

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Mueang, , Thailand

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Songkhla, , Thailand

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Adana, , Turkey (Türkiye)

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Barcelona, , Spain

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Barcelona, , Spain

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Lugo, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Málaga, , Spain

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Santander, , Spain

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Seville, , Spain

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Taichung, , Taiwan

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Taichung, , Taiwan

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Tainan City, , Taiwan

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Birmingham, Alabama, United States

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Bakersfield, California, United States

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Fullerton, California, United States

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Los Angeles, California, United States

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Salinas, California, United States

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Santa Barbara, California, United States

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Truckee, California, United States

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New Haven, Connecticut, United States

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Washington D.C., District of Columbia, United States

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Orlando, Florida, United States

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Chicago, Illinois, United States

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Fort Wayne, Indiana, United States

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Kansas City, Kansas, United States

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Louisville, Kentucky, United States

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New Orleans, Louisiana, United States

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Grand Rapids, Michigan, United States

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Bozeman, Montana, United States

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New Hyde Park, New York, United States

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New York, New York, United States

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New York, New York, United States

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Rochester, New York, United States

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Germantown, Tennessee, United States

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Fort Worth, Texas, United States

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Buenos Aires, , Argentina

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Buenos Aires, , Argentina

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Ciudad de Buenos Aires, , Argentina

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Ciudad de Buenos Aires, , Argentina

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Rosario, , Argentina

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Box Hill, , Australia

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Elizabeth Vale, , Australia

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Kogarah, , Australia

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Macquarie University, , Australia

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Murdoch, , Australia

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Orange, , Australia

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South Brisbane, , Australia

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St Albans, , Australia

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Curitiba, , Brazil

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Fortaleza, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Ribeirão Preto, , Brazil

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Rio de Janeiro, , Brazil

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Rio de Janeiro, , Brazil

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Salvador, , Brazil

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Santa Maria, , Brazil

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São José do Rio Preto, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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Pleven, , Bulgaria

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Plovdiv, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Calgary, Alberta, Canada

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Edmonton, Alberta, Canada

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Vancouver, British Columbia, Canada

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Hamilton, Ontario, Canada

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Ottawa, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Beijing, , China

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Beijing, , China

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Beijing, , China

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Changchun, , China

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Changsha, , China

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Changsha, , China

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Chongqing, , China

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Chongqing, , China

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Dalian, , China

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Guangzhou, , China

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Guangzhou, , China

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Hangzhou, , China

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Hangzhou, , China

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Hangzhou, , China

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Hangzhou, , China

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Jinan, , China

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Nanchang, , China

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Nanjing, , China

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Shanghai, , China

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Shanghai, , China

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Shenyang, , China

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Suzhou, , China

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Tianjin, , China

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Tianjin, , China

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Ürümqi, , China

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Wuhan, , China

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Xi'an, , China

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Brno, , Czechia

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Hradec Králové, , Czechia

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Olomouc, , Czechia

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Ostrava, , Czechia

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Prague, , Czechia

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Prague, , Czechia

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Prague, , Czechia

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Budapest, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Debrecen, , Hungary

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Győr, , Hungary

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Kecskemét, , Hungary

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Szolnok, , Hungary

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Gurgaon, , India

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Hubli, , India

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Kolkata, , India

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Mysuru, , India

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Nagpur, , India

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Nashik, , India

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New Delhi, , India

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New Delhi, , India

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Pune, , India

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Haifa, , Israel

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Jerusalem, , Israel

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Kfar Saba, , Israel

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Petah Tikva, , Israel

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Ramat Gan, , Israel

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Adapazarı, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Edirne, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Hanoi, , Vietnam

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Hanoi, , Vietnam

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Hà Nội, , Vietnam

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Ho Chi Minh City, , Vietnam

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Countries

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United States Argentina Australia Brazil Bulgaria Canada China Czechia Hungary India Israel Italy Japan Philippines Poland Russia South Korea Spain Taiwan Thailand Turkey (Türkiye) Vietnam

Other Identifiers

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2018-001883-48

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D933SC00001

Identifier Type: -

Identifier Source: org_study_id

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