Biliary Tract NeoplasmsPhase 3TOPAZ-1NCT03875235
Durvalumab or Placebo in Combination With Gemcitabine/Cisplatin in Patients With 1st Line Advanced Biliary Tract Cancer (TOPAZ-1)
A Phase 3 study testing Durvalumab in people with Biliary Tract Neoplasms, run by AstraZeneca at 126 sites in 17 countries.
Trial summary
Durvalumab or Placebo in Combination With Gemcitabine/Cisplatin in Patients With 1st Line Advanced Biliary Tract Cancer (TOPAZ-1). Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Biliary Tract Neoplasms
- What is being tested?
- Durvalumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 810 participants
- Where
- 126 sitesin 17 countries
- Study dates
- 16 Apr 2019to 16 May 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
126 sites in 17 countries.
126 sites in 17 countries
China22 sites
Research Site
Baoding, 071000
Research Site
Beijing, 100021
Research Site
Beijing, 100142
Research Site
Bengbu, 233004
Research Site
Chongqing, 400038
Research Site
Foshan, 528000
Research Site
Guangzhou, 510062
Research Site
Hangzhou, 310003
Research Site
Hangzhou, 310009
Research Site
Harbin, 150081
Research Site
Hefei, 230001
Research Site
Hefei, 230601
Research Site
Jinan, 250014
Research Site
Nanchang, 330006
Research Site
Nanjing, 210002
Research Site
Shandong
Research Site
Shanghai, 200032
Research Site
Shenyang, 100003
Research Site
Suzhou, 215004
Research Site
Xi'an, 710061
Research Site
Zhengzhou, 450008
Research Site
Zhuhai, 519000
United States15 sites
Research Site
Burlington, Massachusetts, 01805
Research Site
Chapel Hill, North Carolina, 27514
Research Site
Chattanooga, Tennessee, 37404
Research Site
Fort Myers, Florida, 33905
Research Site
Los Angeles, California, 90027
Research Site
Louisville, Kentucky, 40202
Research Site
Nashville, Tennessee, 37203
Research Site
Orange, California, 92868
Research Site
Philadelphia, Pennsylvania, 19111
Research Site
Portland, Oregon, 97213
Research Site
Seattle, Washington, 98109
Research Site
St Louis, Missouri, 63110
Research Site
St. Petersburg, Florida, 33705
Research Site
Washington D.C., District of Columbia, 20007
Research Site
Westwood, Kansas, 66205
Japan8 sites
Research Site
Chūōku, 104-0045
Research Site
Kashiwa, 227-8577
Research Site
Kitaadachi-gun, 362-0806
Research Site
Mitaka-shi, 181-8611
Research Site
Osaka, 541-8567
Research Site
Suita-shi, 565-0871
Research Site
Wakayama, 641-8510
Research Site
Yokohama, 241-8515
Russia8 sites
Research Site
Barnaul, 656049
Research Site
Kostroma, 156005
Research Site
Moscow, 115478
Research Site
Moscow, 121467
Research Site
Moscow, 125284
Research Site
Omsk, 644033
Research Site
Saint Petersburg, 197022
Research Site
Saint Petersburg, 197758
Taiwan8 sites
Research Site
Chiayi City, 613
Research Site
Kaohsiung City, 82445
Research Site
Kaohsiung City, 83301
Research Site
Taichung, 40705
Research Site
Tainan, 704
Research Site
Taipei, 10050
Research Site
Taipei, 11217
Research Site
Taoyuan, 333
United Kingdom8 sites
Research Site
Bristol, BS2 8ED
Research Site
Cambridge, CB2 0QQ
Research Site
London, NW3 2QG
Research Site
London, W12 0NN
Research Site
Manchester, M20 4BX
Research Site
Oxford, OX3 7LE
Research Site
Romford, RM7 0AG
Research Site
Sheffield, S10 2SJ
Argentina7 sites
Research Site
Buenos Aires, C1118AAT
Research Site
CABA, C1012AAR
Research Site
CABA, C1019ABS
Research Site
Ciudad de Buenos Aires, 1280
Research Site
Ciudad de Buenos Aires, C1426ANZ
Research Site
Rosario, 2000
Research Site
San Salvador de Jujuy, 4600
France7 sites
Research Site
Clichy, 92210
Research Site
Dijon, 21079
Research Site
Montpellier, 34295
Research Site
Nice, 6189
Research Site
Paris, 75571
Research Site
Pessac, 33604
Research Site
Poitiers, 86021
Italy6 sites
Research Site
Faenza, 48018
Research Site
Florence, 50134
Research Site
Milan, 20132
Research Site
Naples, 80131
Research Site
Roma, 00168
Research Site
Verona, 37134
Poland6 sites
Research Site
Gdansk, 80-952
Research Site
Lodz, 93-513
Research Site
Olsztyn, 10-228
Research Site
Poznan, 60-780
Research Site
Warsaw, 02-106
Research Site
Wroclaw, 50-556
South Korea6 sites
Research Site
Seongnam-si, 13620
Research Site
Seoul, 03080
Research Site
Seoul, 03722
Research Site
Seoul, 06351
Research Site
Seoul, 06591
Research Site
Seoul, 152-703
Thailand6 sites
Research Site
Bangkok, 10330
Research Site
Bangkok, 10400
Research Site
Hat Yai, 90110
Research Site
Khon Kaen, 40002
Research Site
Muang, 50200
Research Site
Si Sa Ket, 33000
Bulgaria5 sites
Research Site
Burgas, 8000
Research Site
Sofia, 1330
Research Site
Sofia, 1407
Research Site
Sofia, 1606
Research Site
Varna, 9010
Hong Kong4 sites
Research Site
Hong Kong, 00000
Research Site
Hong Kong, 150001
Research Site
Hong Kong
Research Site
Kowloon
India4 sites
Research Site
Gūrgaon, 122001
Research Site
Kolkata, 700160
Research Site
Mumbai, 400012
Research Site
New Delhi, 110085
Turkey (Türkiye)4 sites
Research Site
Ankara, 06100
Research Site
Istanbul, 34030
Research Site
Izmir, 35100
Research Site
Mersin, 33110
About this study
Official title: 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
Durvalumab or Placebo in Combination With Gemcitabine/Cisplatin in Patients With 1st Line Advanced Biliary Tract Cancer (TOPAZ-1).
Read the detailed description
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.
- Conditions
- Biliary Tract Neoplasms
- Being tested
- Durvalumab, Placebo
- Keywords
- First-Line Advanced Biliary Tract Cancers (BTC), Durvalumab, Gemcitabine/Cisplatin, Placebo
- Medical subject headings
- Biliary Tract Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | Durvalumab + Gemcitabine + Cisplatin Receives: Drug: Durvalumab |
| Placebo Arm | Placebo comparator | Placebo + Gemcitabine + Cisplatin Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: 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).
Measured: 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)
PFS based on investigator assessments according to RECIST version 1.1 was defined as time from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression. Progression (i.e., PD) was defined as at least a 20% increase in the sum of diameters of target lesions (TLs) and an absolute increase of ≥5mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters, or a measurable increase in a non-target lesion, or the appearance of new lesions. Median PFS was calculated using the Kaplan-Meier technique.
Measured: 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
PFS based on investigator assessments according to RECIST version 1.1 was defined as time from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression. Progression (i.e., PD) was defined as at least a 20% increase in the sum of diameters of target lesions (TLs) and an absolute increase of ≥5mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters, or a measurable increase in a non-target lesion, or the appearance of new lesions. Median PFS was calculated using the Kaplan-Meier technique.
Measured: 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
PFS based on investigator assessments according to RECIST version 1.1 was defined as time from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression. Progression (i.e., PD) was defined as at least a 20% increase in the sum of diameters of target lesions (TLs) and an absolute increase of ≥5mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters, or a measurable increase in a non-target lesion, or the appearance of new lesions. Median PFS was calculated using the Kaplan-Meier technique.
Measured: 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)
Disease assessments based on investigator assessments were determined by using RECIST version 1.1 guidelines. The ORR was defined as the percentage of patients with confirmed complete response (CR) or confirmed partial response (PR). The CR was defined as disappearance of all target and non-target lesions and no new lesions. The PR was defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesion. A confirmed CR or PR was defined as 2 CRs or 2 PRs with no evidence of progression in-between. Patients who discontinued randomized treatment without progression, received a subsequent anti-cancer therapy and then responded were not included as responders for ORR.
Measured: 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)
The DoR was defined as the time from the date of first documented OR (confirmed CR or confirmed PR) until date of documented progression (PD) based on investigator assessments by using RECIST version 1.1 or death in absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1) . A confirmed CR was defined in above outcome measures. The PD was defined at least 20% increase in sum of diameters of target lesions (compared with nadir at 2 consecutive visits with an absolute increase of 5 mm), unequivocal progression of existing non-target lesions or new lesion. For participants who were alive and no documented PD at the time of data cutoff for analysis, DoR was censored at the last evaluable disease assessment date. Median DoR was calculated using Kaplan-Meier method.
Measured: 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.
Duration of Response (DoR): Percentage Remaining in Response at 9 Months
The DoR was defined as the time from the date of first documented OR (confirmed CR or confirmed PR) until date of documented progression (PD) based on investigator assessments by using RECIST version 1.1 or death in absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1) . A confirmed CR was defined in above outcome measures. The PD was defined at least 20% increase in sum of diameters of target lesions (compared with nadir at 2 consecutive visits with an absolute increase of 5 mm), unequivocal progression of existing non-target lesions or new lesion. For participants who were alive and no documented PD at the time of data cutoff for analysis, DoR was censored at the last evaluable disease assessment date. Median DoR was calculated using Kaplan-Meier method.
Measured: 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. Calculated at 9 months using the Kaplan-Meier technique
Duration of Response (DoR): Percentage Remaining in Response at 12 Months
The DoR was defined as the time from the date of first documented OR (confirmed CR or confirmed PR) until date of documented progression (PD) based on investigator assessments by using RECIST version 1.1 or death in absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1) . A confirmed CR was defined in above outcome measures. The PD was defined at least 20% increase in sum of diameters of target lesions (compared with nadir at 2 consecutive visits with an absolute increase of 5 mm), unequivocal progression of existing non-target lesions or new lesion. For participants who were alive and no documented PD at the time of data cutoff for analysis, DoR was censored at the last evaluable disease assessment date. Median DoR was calculated using Kaplan-Meier method.
Measured: 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. Calculated at 12 months using the Kaplan-Meier technique
Disease Control Rate (DCR) - Overall
Disease control rate based on investigator assessments according to RECIST version 1.1 was defined as the rate of best objective response of complete response (CR), partial response (PR) or stable disease (SD).
Measured: 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.
Disease Control Rate (DCR) - 24 Weeks
Disease control rate based on investigator assessments according to RECIST version 1.1 was defined as the rate of best objective response of complete response (CR) or partial response (PR) by week 24 or who have stable disease (SD) at least 24 weeks following start of treatment.
Measured: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization.
Disease Control Rate (DCR) - 32 Weeks
Disease control rate based on investigator assessments according to RECIST version 1.1 was defined as the rate of best objective response of complete response (CR) or partial response (PR) by week 32 or who have stable disease (SD) at least 32 weeks following start of treatment.
Measured: 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.
Disease Control Rate (DCR) - 48 Weeks
Disease control rate based on investigator assessments according to RECIST version 1.1 was defined as the rate of best objective response of complete response (CR) or partial response (PR) by week 48 or who have stable disease (SD) at least 48 weeks following start of treatment.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2019
- Study start16 Apr 2019
- Primary completion11 Aug 2021
- Study completion16 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Biliary Tract NeoplasmsStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Durvalumab in Combination with Gemcitabine plus Cisplatin Placebo in Combination with Gemcitabine plus Cisplatin
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 810 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gordon Cohen, Study director, AstraZeneca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03875235
- Sponsor's protocol ID
- D933AC00001
- Other IDs
- 2023-507405-34-00, 2018-004688-30, 2018, 2023
- Acronym
- TOPAZ-1
- Status last verified
- Aug 2026
- First submitted
- 13 Mar 2019
- Last updated
- 26 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Oh DY, He AR, Qin S, Chen LT, Okusaka T, Griffin R, Wang J, Xynos I, Vogel A, Valle JW. Durvalumab Plus Chemotherapy for Advanced Biliary Tract Cancer: A Post Hoc Analysis of the TOPAZ-1 Randomized Clinical Trial. JAMA Oncol. 2026 Jul 9:e262204. doi: 10.1001/jamaoncol.2026.2204. Online ahead of print.
PubMed 42424063Antonuzzo 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.
PubMed 40622010Oh 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.
PubMed 40381735Oh 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.
PubMed 38823398Burris 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.
PubMed 38697156Keller 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.
PubMed 38661512Oh 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.
PubMed 38319896