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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04066491




Registration number
NCT04066491
Ethics application status
Date submitted
22/08/2019
Date registered
26/08/2019

Titles & IDs
Public title
Gemcitabine Plus Cisplatin With or Without Bintrafusp Alfa (M7824) in Participants With 1L BTC
Scientific title
A Phase II/III, Multicenter, Randomized, Placebo-controlled Study of Gemcitabine Plus Cisplatin With or Without Bintrafusp Alfa (M7824) as First-line Treatment of Biliary Tract Cancer
Secondary ID [1] 0 0
2019-001992-35
Secondary ID [2] 0 0
MS200647_0055
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Biliary Tract Cancer 0 0
Cholangiocarcinoma 0 0
Gallbladder Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Biliary tree (gall bladder and bile duct)
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - M7824
Treatment: Drugs - Placebo
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Cisplatin

Experimental: Safety Run-In Part: M7824 + Gemcitabine + Cisplatin -

Experimental: Double-blinded Part: M7824 + Gemcitabine + Cisplatin -

Placebo comparator: Double-blinded Part: Placebo + Gemcitabine + Cisplatin -


Treatment: Drugs: M7824
Participants received intravenous infusion of M7824 at a dose of 2400 milligrams (mg), once every 3 weeks (Q3W) 2 years (in case of Complete Response), otherwise until criterion pre-sepcified in protocol for discontinuation is met, in combination with intravenous infusion of Gemcitabine and Cisplatin at a dose of 1000 milligram per meter square (mg/m\^2) and 25 mg/m\^2 respectively on Day 1 and Day 8 of 21- day cycle, for 8 cycles every 3 weeks.

Treatment: Drugs: Placebo
Participants received intravenous infusion of M7824 matched placebo, once every 3 weeks (Q3W) until 2 years (in case of CR), otherwise until crtiterion pre-sepcified in protocol for discontinuation is met.

Treatment: Drugs: Gemcitabine
Gemcitabine was received intravenously at a dose of 1000 milligram per meter square (mg/m\^2) on Day 1 and Day 8 of 21- day cycle, for 8 cycles every 3 weeks (Q3W).

Treatment: Drugs: Cisplatin
Cisplatin was received intravenously at a dose of 25 mg/m\^2 on Day 1 and Day 8 of 21-day cycle, for 8 cycles every 3 weeks (Q3W).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety Run-in Part: Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
Timepoint [1] 0 0
Day 1 up to Day 21 of Cycle 1 (each Cycle is of 21 days)
Primary outcome [2] 0 0
Double-blind Part: Overall Survival
Timepoint [2] 0 0
Time from study day 1 up to data cutoff (assessed up to 609 days)
Secondary outcome [1] 0 0
Safety Run-in Part: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (SAEs) and Treatment Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0
Timepoint [1] 0 0
Time from first treatment up to data cutoff (assessed up to 609 days)
Secondary outcome [2] 0 0
Safety Run-in Part: Number of Participants With Grade Greater Than or Equal (>=) 3 Laboratory Abnormalities
Timepoint [2] 0 0
Time from first treatment up to data cutoff (assessed up to 609 days)
Secondary outcome [3] 0 0
Double-blind Part: Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)
Timepoint [3] 0 0
Time from randomization of study drug until the first documentation of PD or death, assessed up to 609 days
Secondary outcome [4] 0 0
Double-blind Part: Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)
Timepoint [4] 0 0
Time from randomization of study drug up to data cut off (assessed up to 609 days)
Secondary outcome [5] 0 0
Double-blind Part: Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)
Timepoint [5] 0 0
From first documented objective response to PD or death due to any cause, assessed up to 609 days
Secondary outcome [6] 0 0
Double-blind Part: Durable Response of at Least 6 Months According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator
Timepoint [6] 0 0
Time from first treatment assessed up to 1148 days
Secondary outcome [7] 0 0
Double-blind Part: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (SAEs), Treatment Related TEAEs and Adverse Events of Special Interest (AESIs) According to NCI-CTCAE Version 5.0
Timepoint [7] 0 0
Time from first treatment up to data cutoff (assessed up to 609 days)

Eligibility
Key inclusion criteria
* Are participants with histologically or cytologically confirmed locally advanced or metastatic BTC
* Participants must have available tumor tissue (primary or metastatic) (archival or fresh biopsies) before the first administration of study treatment
* At least 1 measurable lesion according to RECIST 1.1
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 at study entry and at Week 1, Day 1 prior to dosing
* Life expectancy of >= 12 weeks, as judged by the Investigator
* Adequate hematological function, hepatic function, renal function, coagulation function as defined in the protocol
* Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) positive participants must be treated and on a stable dose of antivirals
* Other protocol defined inclusion criteria could apply
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Previous and/or intercurrent cancers
* Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression
* Participants with symptomatic central nervous system (CNS) metastases
* Significant acute or chronic infection including known history of positive test for human immunodeficiency virus (HIV), active tuberculosis, uncontrolled biliary infection and active bacterial or fungal infection requiring systemic therapy (with the exception of hepatitis B and hepatitis C) requiring systemic therapy at study entry and at Week 1 Day 1 prior to dosing.
* Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
* History of or concurrent interstitial lung disease
* History of hypersensitivity reactions to bintrafusp alfa, anaphylaxis, or recent (within 5 months) uncontrolled asthma, cardiovascular/cerebrovascular disease
* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before randomization
* Prior therapy with any antibody/drug targeting T-cell coregulatory proteins (immune checkpoints)
* Other protocol defined exclusion criteria could apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/09/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
10/11/2022
Sample size
Target
Accrual to date
Final
309
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Blacktown Hospital - PARENT - Blacktown
Recruitment hospital [2] 0 0
Monash Health - Clayton
Recruitment hospital [3] 0 0
Epworth Freemasons - Melbourne
Recruitment hospital [4] 0 0
Icon Cancer Care South Brisbane - South Brisbane
Recruitment postcode(s) [1] 0 0
- Blacktown
Recruitment postcode(s) [2] 0 0
- Clayton
Recruitment postcode(s) [3] 0 0
- Melbourne
Recruitment postcode(s) [4] 0 0
- South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Argentina
State/province [8] 0 0
Ciudad Autonoma Buenos Aires
Country [9] 0 0
Argentina
State/province [9] 0 0
La Rioja
Country [10] 0 0
Argentina
State/province [10] 0 0
Salta
Country [11] 0 0
Argentina
State/province [11] 0 0
San Miguel de Tucuman
Country [12] 0 0
Argentina
State/province [12] 0 0
San Salvador de Jujuy
Country [13] 0 0
Brazil
State/province [13] 0 0
Barretos
Country [14] 0 0
Brazil
State/province [14] 0 0
Rio de Janeiro
Country [15] 0 0
Brazil
State/province [15] 0 0
Santo André
Country [16] 0 0
Brazil
State/province [16] 0 0
Sao Jose Rio Preto
Country [17] 0 0
Brazil
State/province [17] 0 0
São Paulo
Country [18] 0 0
Chile
State/province [18] 0 0
La Serena
Country [19] 0 0
Chile
State/province [19] 0 0
Santiago
Country [20] 0 0
Chile
State/province [20] 0 0
Temuco
Country [21] 0 0
China
State/province [21] 0 0
Beijing
Country [22] 0 0
China
State/province [22] 0 0
Chengdu
Country [23] 0 0
China
State/province [23] 0 0
Hangzhou
Country [24] 0 0
China
State/province [24] 0 0
Qingdao
Country [25] 0 0
China
State/province [25] 0 0
Shanghai
Country [26] 0 0
China
State/province [26] 0 0
Suzhou
Country [27] 0 0
China
State/province [27] 0 0
Tianjin
Country [28] 0 0
China
State/province [28] 0 0
Wuhan
Country [29] 0 0
France
State/province [29] 0 0
Angers Cedex 2
Country [30] 0 0
France
State/province [30] 0 0
Dijon cedex
Country [31] 0 0
France
State/province [31] 0 0
Lille cedex
Country [32] 0 0
France
State/province [32] 0 0
Saint Herblain
Country [33] 0 0
France
State/province [33] 0 0
Toulouse Cedex 9
Country [34] 0 0
Germany
State/province [34] 0 0
Berlin
Country [35] 0 0
Germany
State/province [35] 0 0
Bonn
Country [36] 0 0
Germany
State/province [36] 0 0
Dresden
Country [37] 0 0
Germany
State/province [37] 0 0
Frankfurt
Country [38] 0 0
Germany
State/province [38] 0 0
Mainz
Country [39] 0 0
Italy
State/province [39] 0 0
Milano
Country [40] 0 0
Italy
State/province [40] 0 0
Padova
Country [41] 0 0
Italy
State/province [41] 0 0
Roma
Country [42] 0 0
Italy
State/province [42] 0 0
Verona
Country [43] 0 0
Japan
State/province [43] 0 0
Chiba-shi
Country [44] 0 0
Japan
State/province [44] 0 0
Chuo-ku
Country [45] 0 0
Japan
State/province [45] 0 0
Fukuoka-shi
Country [46] 0 0
Japan
State/province [46] 0 0
Kashiwa-shi
Country [47] 0 0
Japan
State/province [47] 0 0
Koto-ku
Country [48] 0 0
Japan
State/province [48] 0 0
Mitaka-shi
Country [49] 0 0
Japan
State/province [49] 0 0
Nagoya-shi
Country [50] 0 0
Japan
State/province [50] 0 0
Osaka-shi
Country [51] 0 0
Japan
State/province [51] 0 0
Osakasayama-shi
Country [52] 0 0
Japan
State/province [52] 0 0
Yokohama-shi
Country [53] 0 0
Korea, Republic of
State/province [53] 0 0
Daejeon
Country [54] 0 0
Korea, Republic of
State/province [54] 0 0
Seongnam-si
Country [55] 0 0
Korea, Republic of
State/province [55] 0 0
Seoul
Country [56] 0 0
Poland
State/province [56] 0 0
Gliwice
Country [57] 0 0
Poland
State/province [57] 0 0
Krakow
Country [58] 0 0
Poland
State/province [58] 0 0
Warszawa
Country [59] 0 0
Poland
State/province [59] 0 0
Zamosc
Country [60] 0 0
Spain
State/province [60] 0 0
Barcelona
Country [61] 0 0
Spain
State/province [61] 0 0
Caceres
Country [62] 0 0
Spain
State/province [62] 0 0
Cordoba
Country [63] 0 0
Spain
State/province [63] 0 0
L'Hospitalet de Llobregat
Country [64] 0 0
Spain
State/province [64] 0 0
Madrid
Country [65] 0 0
Spain
State/province [65] 0 0
Valencia
Country [66] 0 0
Taiwan
State/province [66] 0 0
Kaohsiung
Country [67] 0 0
Taiwan
State/province [67] 0 0
Taichung
Country [68] 0 0
Taiwan
State/province [68] 0 0
Tainan
Country [69] 0 0
Taiwan
State/province [69] 0 0
Taipei
Country [70] 0 0
Taiwan
State/province [70] 0 0
Taoyuan
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
EMD Serono Research & Development Institute, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck KGaA, Darmstadt, Germany
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Responsible
Address 0 0
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union.
Available to whom?
Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://bit.ly/IPD21


What supporting documents are/will be available?




Results publications and other study-related documents

TypeCitations or Other Details
Journal Yoo C, Oh DY, Choi HJ, Kudo M, Ueno M, Kondo S, Ch... [More Details]


Results are available at https://clinicaltrials.gov/study/NCT04066491