Durvalumab or Placebo in Combination With Gemcitabine/Cisplatin in Patients With 1st Line Advanced Biliary Tract Cancer (TOPAZ-1)
TOPAZ-1
A Phase III Randomized, Double-Blind Placebo Controlled, Multi-Regional, International Study of Durvalumab in Combination With Gemcitabine Plus Cisplatin Versus Placebo in Combination With Gemcitabine Plus Cisplatin for Patients With First-Line Advanced Biliary Tract Cancers
3 other identifiers
interventional
810
17 countries
126
Brief Summary
Durvalumab or Placebo in Combination With Gemcitabine/Cisplatin in Patients With 1st Line Advanced Biliary Tract Cancer (TOPAZ-1).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Apr 2019
Longer than P75 for phase_3
126 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 13, 2019
CompletedFirst Posted
Study publicly available on registry
March 14, 2019
CompletedStudy Start
First participant enrolled
April 16, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 11, 2021
CompletedResults Posted
Study results publicly available
April 13, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
May 16, 2027
ExpectedMarch 19, 2026
February 1, 2026
2.3 years
March 13, 2019
August 10, 2022
February 26, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Overall Survival (OS)
Overall Survival (OS) was defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. The second interim analysis was pre-specified after approximately 397 OS events occurred in both arms (59% maturity).
From date of randomization until death due to any cause. Assessed up to maximum of approximately 27 months (from date of randomization to primary analysis data cut-off)
Overall Survival (OS) Rate at 18 Months
Overall Survival (OS) was defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. The second interim analysis was pre-specified after approximately 397 OS events occurred in both arms (59% maturity).
From date of randomization until death due to any cause. Calculated at 18 months using the Kaplan-Meier technique.
Overall Survival (OS) Rate at 24 Months
Overall Survival (OS) was defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. The second interim analysis was pre-specified after approximately 397 OS events occurred in both arms (59% maturity).
From date of randomization until death due to any cause. Calculated at 24 months using the Kaplan-Meier technique.
Secondary Outcomes (11)
Progression-free Survival (PFS)
Tumor assessments every 6 weeks after randomization for the first 24 weeks and then every 8 weeks thereafter until date of RECIST 1.1 defined radiological progressive disease or death. Assessed up to maximum of approximately 27 months.
Progression-free Survival (PFS) Rate at 9 Months
Tumor assessments every 6 weeks after randomization for the first 24 weeks and then every 8 weeks thereafter until date of RECIST 1.1 defined radiological progressive disease or death. Calculated at 9 months using the Kaplan-Meier technique.
Progression-free Survival (PFS) Rate at 12 Months
Tumor assessments every 6 weeks after randomization for the first 24 weeks and then every 8 weeks thereafter until date of RECIST 1.1 defined radiological progressive disease or death. Calculated at 12 months using the Kaplan-Meier technique
Objective Response Rate (ORR)
Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter. Assessed up to maximum of approximately 27 months.
Duration of Response (DoR)
Tumor assessments (per RECIST 1.1) every 6 weeks for first 24 weeks relative to the date of randomization and then every 8 weeks thereafter. Assessed up to maximum of approximately 27 months.
- +6 more secondary outcomes
Study Arms (2)
Treatment Arm
EXPERIMENTALDurvalumab + Gemcitabine + Cisplatin
Placebo Arm
PLACEBO COMPARATORPlacebo + Gemcitabine + Cisplatin
Interventions
IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.
IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.
Eligibility Criteria
You may qualify if:
- Histologically confirmed, unresectable advanced or metastatic biliary tract, including cholangiocarcinoma (intrahepatic or extrahepatic) and gallbladder carcinoma.
- Patients with previously untreated disease if unresectable or metastatic at initial diagnosis will be eligible.
- Patient with recurrent disease \>6 months after curative surgery or \>6 months after the completion of adjuvant therapy (chemotherapy and/or radiation) will be eligible.
- WHO/ECOG PS of 0 or 1
You may not qualify if:
- History of another primary malignancy
- Brain metastases or spinal cord compression
- Uncontrolled intercurrent illness
- Major surgical procedure within 28 days prior to the first dose of IP.
- Prior locoregional therapy such as radioembolization
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (126)
Research Site
Los Angeles, California, 90027, United States
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Orange, California, 92868, United States
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Washington D.C., District of Columbia, 20007, United States
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Fort Myers, Florida, 33905, United States
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St. Petersburg, Florida, 33705, United States
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Westwood, Kansas, 66205, United States
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Louisville, Kentucky, 40202, United States
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Burlington, Massachusetts, 01805, United States
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St Louis, Missouri, 63110, United States
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Chapel Hill, North Carolina, 27514, United States
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Portland, Oregon, 97213, United States
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Philadelphia, Pennsylvania, 19111, United States
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Chattanooga, Tennessee, 37404, United States
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Nashville, Tennessee, 37203, United States
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Seattle, Washington, 98109, United States
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Buenos Aires, C1118AAT, Argentina
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CABA, C1012AAR, Argentina
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CABA, C1019ABS, Argentina
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Ciudad de Buenos Aires, 1280, Argentina
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Ciudad de Buenos Aires, C1426ANZ, Argentina
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Rosario, 2000, Argentina
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San Salvador de Jujuy, 4600, Argentina
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Burgas, 8000, Bulgaria
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Sofia, 1330, Bulgaria
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Sofia, 1407, Bulgaria
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Sofia, 1606, Bulgaria
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Varna, 9010, Bulgaria
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Santiago, 7630370, Chile
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Temuco, 4810218, Chile
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Baoding, 071000, China
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Beijing, 100021, China
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Beijing, 100142, China
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Bengbu, 233004, China
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Chongqing, 400038, China
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Foshan, 528000, China
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Guangzhou, 510062, China
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Hangzhou, 310003, China
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Hangzhou, 310009, China
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Harbin, 150081, China
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Hefei, 230001, China
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Hefei, 230601, China
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Jinan, 250014, China
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Nanchang, 330006, China
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Nanjing, 210002, China
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Shandong, China
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Shanghai, 200032, China
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Shenyang, 100003, China
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Suzhou, 215004, China
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Xi'an, 710061, China
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Zhengzhou, 450008, China
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Zhuhai, 519000, China
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Clichy, 92210, France
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Dijon, 21079, France
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Montpellier, 34295, France
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Nice, 6189, France
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Paris, 75571, France
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Pessac, 33604, France
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Poitiers, 86021, France
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Hong Kong, 00000, Hong Kong
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Hong Kong, 150001, Hong Kong
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Hong Kong, Hong Kong
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Kowloon, Hong Kong
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Gūrgaon, 122001, India
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Kolkata, 700160, India
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Mumbai, 400012, India
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New Delhi, 110085, India
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Faenza, 48018, Italy
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Florence, 50134, Italy
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Milan, 20132, Italy
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Naples, 80131, Italy
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Roma, 00168, Italy
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Verona, 37134, Italy
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Chūōku, 104-0045, Japan
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Kashiwa, 227-8577, Japan
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Kitaadachi-gun, 362-0806, Japan
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Mitaka-shi, 181-8611, Japan
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Osaka, 541-8567, Japan
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Suita-shi, 565-0871, Japan
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Wakayama, 641-8510, Japan
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Yokohama, 241-8515, Japan
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Gdansk, 80-952, Poland
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Lodz, 93-513, Poland
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Olsztyn, 10-228, Poland
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Poznan, 60-780, Poland
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Warsaw, 02-106, Poland
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Wroclaw, 50-556, Poland
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Barnaul, 656049, Russia
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Kostroma, 156005, Russia
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Moscow, 115478, Russia
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Moscow, 121467, Russia
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Moscow, 125284, Russia
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Omsk, 644033, Russia
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Saint Petersburg, 197022, Russia
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Saint Petersburg, 197758, Russia
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Seongnam-si, 13620, South Korea
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Seoul, 03080, South Korea
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Seoul, 03722, South Korea
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Seoul, 06351, South Korea
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Seoul, 06591, South Korea
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Seoul, 152-703, South Korea
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Chiayi City, 613, Taiwan
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Kaohsiung City, 82445, Taiwan
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Kaohsiung City, 83301, Taiwan
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Taichung, 40705, Taiwan
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Tainan, 704, Taiwan
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Taipei, 10050, Taiwan
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Taipei, 11217, Taiwan
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Taoyuan District, 333, Taiwan
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Bangkok, 10330, Thailand
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Bangkok, 10400, Thailand
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Hat Yai, 90110, Thailand
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Khon Kaen, 40002, Thailand
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Muang, 50200, Thailand
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Si Sa Ket, 33000, Thailand
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Ankara, 06100, Turkey (Türkiye)
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Istanbul, 34030, Turkey (Türkiye)
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Izmir, 35100, Turkey (Türkiye)
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Mersin, 33110, Turkey (Türkiye)
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Bristol, BS2 8ED, United Kingdom
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Cambridge, CB2 0QQ, United Kingdom
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London, NW3 2QG, United Kingdom
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London, W12 0NN, United Kingdom
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Manchester, M20 4BX, United Kingdom
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Oxford, OX3 7LE, United Kingdom
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Romford, RM7 0AG, United Kingdom
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Sheffield, S10 2SJ, United Kingdom
Related Publications (6)
Antonuzzo L, Takahashi H, Park JO, Sookprasert A, Gillmore R, Yang SS, Cundom J, Petrova M, Vaccaro G, Holmblad M, Zotkiewicz M, Wang J, Rokutanda N, Oh DY. Immune-mediated adverse events in the randomized phase 3 TOPAZ-1 study of durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. Oncologist. 2025 Jul 4;30(7):oyaf148. doi: 10.1093/oncolo/oyaf148.
PMID: 40622010DERIVEDOh DY, He AR, Qin S, Chen LT, Okusaka T, Kim JW, Suksombooncharoen T, Lee MA, Kitano M, Burris HA, Bouattour M, Tanasanvimon S, Zaucha R, Avallone A, Cundom J, Kuzko A, Wang J, Xynos I, Vogel A, Valle JW. Durvalumab plus chemotherapy in advanced biliary tract cancer: 3-year overall survival update from the phase III TOPAZ-1 study. J Hepatol. 2025 Nov;83(5):1092-1101. doi: 10.1016/j.jhep.2025.05.003. Epub 2025 May 15.
PMID: 40381735DERIVEDOh DY, He AR, Bouattour M, Okusaka T, Qin S, Chen LT, Kitano M, Lee CK, Kim JW, Chen MH, Suksombooncharoen T, Ikeda M, Lee MA, Chen JS, Potemski P, Burris HA 3rd, Ostwal V, Tanasanvimon S, Morizane C, Zaucha RE, McNamara MG, Avallone A, Cundom JE, Breder V, Tan B, Shimizu S, Tougeron D, Evesque L, Petrova M, Zhen DB, Gillmore R, Gupta VG, Dayyani F, Park JO, Buchschacher GL Jr, Rey F, Kim H, Wang J, Morgan C, Rokutanda N, Zotkiewicz M, Vogel A, Valle JW. Durvalumab or placebo plus gemcitabine and cisplatin in participants with advanced biliary tract cancer (TOPAZ-1): updated overall survival from a randomised phase 3 study. Lancet Gastroenterol Hepatol. 2024 Aug;9(8):694-704. doi: 10.1016/S2468-1253(24)00095-5. Epub 2024 May 29.
PMID: 38823398DERIVEDBurris HA 3rd, Okusaka T, Vogel A, Lee MA, Takahashi H, Breder V, Blanc JF, Li J, Bachini M, Zotkiewicz M, Abraham J, Patel N, Wang J, Ali M, Rokutanda N, Cohen G, Oh DY. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer (TOPAZ-1): patient-reported outcomes from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2024 May;25(5):626-635. doi: 10.1016/S1470-2045(24)00082-2.
PMID: 38697156DERIVEDKeller HR, Fluke L, Forrester JA, Wolf RF. Identifying Indications for Neoadjuvant Therapy in Cholangiocarcinoma. Oncology (Williston Park). 2024 Apr 11;38(4):160-162. doi: 10.46883/2024.25921017.
PMID: 38661512DERIVEDOh DY, Ruth He A, Qin S, Chen LT, Okusaka T, Vogel A, Kim JW, Suksombooncharoen T, Ah Lee M, Kitano M, Burris H, Bouattour M, Tanasanvimon S, McNamara MG, Zaucha R, Avallone A, Tan B, Cundom J, Lee CK, Takahashi H, Ikeda M, Chen JS, Wang J, Makowsky M, Rokutanda N, He P, Kurland JF, Cohen G, Valle JW. Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer. NEJM Evid. 2022 Aug;1(8):EVIDoa2200015. doi: 10.1056/EVIDoa2200015. Epub 2022 Jun 1.
PMID: 38319896DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca Clinical Study Information Center
Study Officials
- STUDY DIRECTOR
Gordon Cohen
AstraZeneca
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 13, 2019
First Posted
March 14, 2019
Study Start
April 16, 2019
Primary Completion
August 11, 2021
Study Completion (Estimated)
May 16, 2027
Last Updated
March 19, 2026
Results First Posted
April 13, 2023
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.