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Biliary Tract CancerPhase 2NCT04677504

A Study of Atezolizumab With or Without Bevacizumab in Combination With Cisplatin Plus Gemcitabine in Patients With Untreated, Advanced Biliary Tract Cancer

A Phase 2 study testing Atezolizumab, Bevacizumab and Cisplatin in people with Biliary Tract Cancer, run by Hoffmann-La Roche at 49 sites in 13 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study will evaluate the efficacy and safety of atezolizumab with bevacizumab in combination with cisplatin and gemcitabine(CisGem), compared with atezolizumab in combination with CisGem, in participants with advanced biliary tract cancer (BTC) who have not received prior systemic therapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Biliary Tract Cancer
What is being tested?
Atezolizumab, Bevacizumab and Cisplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
162 participants
Where
49 sitesin 13 countries
Study dates
23 Feb 2021to 25 Aug 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Considered to be eligible to receive platinum-based chemotherapy, in the investigator's judgment
  • Documentation of recurrent/metastatic or locally advanced unresectable disease based on computed tomography (CT) or magnetic resonance imaging (MRI) scans
  • Histologically or cytologically confirmed diagnosis of iCCA, eCCA, or GBC
  • No prior systemic therapy for advanced BTC
  • At least one measurable untreated lesion (per RECIST v1.1)
  • Adequate biliary drainage with no evidence of ongoing infection
Show all 11Show fewer
  • Eastern Cooperative Oncology Group Performance Status of 0 or 1
  • Life expectancy of > 3 months
  • Adequate hematologic and end-organ function
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm

Who cannot join

  • Recurrent disease <=6 months after curative surgery or <= 6 months after the completion of adjuvant therapy
  • Prior local regional therapy such as radioembolization
  • Combined or mixed hepatocellular/cholangiocarcinoma
  • Clinically significant hepatic encephalopathy within the 12 months prior to Day 1 of Cycle 1
  • National Cancer Institute Common Terminoogy Criteria for Adverse Events Grade >= 2 peripheral neuropathy
  • Prior bleeding event due to untreated or incompletely treated esophageal and/or gastric varices within 6 months prior to Day 1 of Cycle 1
Show all 22Show fewer
  • Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of atezolizumab or within 6 months after the final dose of bevacizumab, cisplatin or gemcitabine
  • Active or history of autoimmune disease or immune deficiency
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
  • History of malignancy other than BTC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
  • Symptomatic, untreated, or actively progressing CNS metastases
  • For patients with lung metastases, if one of the following criteria applies: Large, centrally located pulmonary metastases; Clear tumor infiltration into the thoracic great vessels seen on imaging; Clear cavitation of pulmonary lesions seen on imaging
  • Active tuberculosis
  • Co-infection with HBV and HCV
  • Treatment with systemic immunostimulatory agents or immunosuppressive medication
  • Inadequately controlled arterial hypertension
  • History of hypertensive crisis or hypertensive encephalopathy
  • Significant vascular disease
  • Evidence of bleeding diathesis or significant coagulopathy
  • Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
  • Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID)
  • Preexisting renal impairment, myelosuppression, or hearing impairment

Trial locations and contacts

49 sites in 13 countries.

49 sites in 13 countries

United States5 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • University of Virginia

    Charlottesville, Virginia, 22903

  • City of Hope Cancer Center

    Duarte, California, 91010

  • Duke Cancer Center

    Durham, North Carolina, 27710

  • Sarah Cannon Research Institute / Tennessee Oncology

    Nashville, Tennessee, 37203

Other trials in United States

Poland5 sites

  • SP ZOZ Wojewódzki Szpital Specjalistyczny nr 4; Oddzial Onkologii Klinicznej

    Bytom, 41-902

  • Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii

    Gdansk, 80-214

  • Szpital Wojewódzki im. Miko?aja Kopernika; Oddzia? Dzienny Chemioterapii

    Koszalin, 75-581

  • NIO im Marii Sklodowskiej-Curie; Klinika Onkologii i Radioterapii

    Warsaw, 02-034

  • Dolno?l?skie Centrum Onkologii; Oddzia? Onkologii Klinicznej i Chemioterapii

    Wroc?aw, 53-413

Other trials in Poland

South Korea5 sites

  • CHA Bundang Medical Center

    Gyeonggi-do, 13496

  • Seoul National University Bundang Hospital

    Seongnam-si, 463-707

  • Seoul National University Hospital

    Seoul, 03080

  • Asan Medical Center

    Seoul, 05505

  • Samsung Medical Center

    Seoul, 06351

Other trials in South Korea

Spain5 sites

  • Hospital Universitari Vall d'Hebron; Oncology

    Barcelona, 08035

  • Hospital Ramon y Cajal; Servicio de Oncologia

    Madrid, 28034

  • Complejo Hospitalario de Orense; Servicio de Oncologia

    Ourense, 32005

  • Complejo Hospitalario de Navarra; Servicio de Oncologia

    Pamplona, Navarre, 31008

  • Hospital Universitario Miguel Servet; Servicio Oncologia

    Zaragoza, 50009

Other trials in Spain

Italy4 sites

  • Azienda Ospedaliero Universitaria di Bologna; Istituto di Ematologia "Lorenzo e Ariosto Seragnoli"

    Bologna, Emilia-Romagna, 40139

  • Fondazione Pascale; U.O. Sperimentazioni Cliniche

    Naples, Campania, 80100

  • IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II

    Padova, Veneto, 35128

  • Istituto Clinico Humanitas - Humanitas Cancer Center

    Rozzano, Sicily, 20089

Other trials in Italy

Russia4 sites

  • FSBI "National Medical Research Center of Oncology N.N. Blokhin?

    Moscow, Moscow Oblast, 115478

  • First Moscow State Medical University n.a. I.M. Sechenov

    Moscow, Moscow Oblast, 119991

  • SBIH "Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM"

    Moskva, Moscow Oblast, 111123

  • GBUZ Saint Petersburg Clinical Research Center of Specialized Types of Care (Oncology)

    Saint Petersburg, Sankt-Peterburg, 197758

Other trials in Russia

Turkey (Türkiye)4 sites

  • Adana Ac?badem Hospital Oncology Department

    Adana, 01130

  • Memorial Ankara Hastanesi

    Ankara, 06520

  • Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department

    Malatya, 44280

  • Koc Universitesi Hastanesi; T?bbi Onkoloji

    Zeyt?nburnu, 34010

Other trials in Turkey (Türkiye)

United Kingdom4 sites

  • Beatson West of Scotland Cancer Centre

    Glasgow, G12 0YN

  • Royal Free Hospital

    London, NW3 2QS

  • Churchill Hospital

    Oxford, OX3 7LJ

  • Royal Marsden Hospital (Sutton)

    Sutton, SM2 5PT

Other trials in United Kingdom

China3 sites

  • Nanfang Hospital, Southern Medical University

    Guangzhou, 510515

  • Sir Run Run Shaw Hospital Zhejiang University

    Hangzhou, 310016

  • Zhongshan Hospital Fudan University

    Shanghai, 200032

Other trials in China

Thailand3 sites

  • Maharaj Nakorn Chiang Mai Hosp; Oncology Unit

    Chiang Mai, 50200

  • Srinagarind Hospital; Medical Oncology Unit

    Khon Kaen, 40002

  • Sunpasitthiprasong Hospital; Oncology and/or Hematology

    Ubon Ratchathani, 34000

Other trials in Thailand

Ukraine3 sites

  • SI Institute of general&urgent surgery n/a Zaytseva V.T NAMSU

    Kharkiv, Kharkiv Governorate, 61018

  • ?Kharkov Regional Oncology Center

    Kharkiv, Kharkiv Governorate, 61070

  • SI "Shalimov National Institute of Surgery and Transplantation" of Nat.Acad of Med.Sci of Ukraine

    Kyiv, KIEV Governorate, 03126

Other trials in Ukraine

Hong Kong2 sites

  • Queen Mary Hospital; Dept. Of Haematology & Oncology

    Hong Kong

  • Prince of Wales Hosp; Dept. Of Clinical Onc

    Shatin

Other trials in Hong Kong

Taiwan2 sites

  • National Taiwan Uni Hospital; Dept of Oncology

    Taipei, 100

  • Taipei Veterans General Hospital; Department of Oncology

    Taipei, 112201

Other trials in Taiwan

About this study

Official title: A Phase II, Randomized, Double-Blind Placebo-Controlled Study of Atezolizumab With or Without Bevacizumab in Combination With Cisplatin Plus Gemcitabine in Patients With Untreated, Advanced Biliary Tract Cancer

This study will evaluate the efficacy and safety of atezolizumab with bevacizumab in combination with cisplatin and gemcitabine(CisGem), compared with atezolizumab in combination with CisGem, in participants with advanced biliary tract cancer (BTC) who have not received prior systemic therapy. Treatment will consist of a chemotherapy combination phase followed by a cancer immunotherapy (CIT)/placebo phase.

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.

  • AtezolizumabDrug

    Also called Tecentriq

    Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.

  • BevacizumabDrug

    Also called Avastin

    Bevacizumab will be administered at a dose of 15 mg/kg intravenously on Day 1 of each 21-day cycle after atezolizumab.

  • PlaceboOther

    Placebo matching bevacizumab will be administered intravenously on Day 1 of each 21-day cycle after atezolizumab.

  • CisplatinDrug

    Cisplatin will be administered intravenously at a dose of 25 mg/m^2 on Days 1 and 8 of each 21-day cycle for Cycles 1-8.

  • GemcitabineDrug

    Gemcitabine will be administered intravenously at a dose of 1000 mg/m^2 on Days 1 and 8 of each 21-day cycle for Cycles 1-8.

Study groups in NCT04677504
Study groupRoleWhat they receive
Arm A: Atezo+Bev+CisGem, followed by Atezo+BevExperimentalParticipants will receive atezolizumab intravenously on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, and clinical status. Participants will receive bevacizumab intravenously on Day 1 of each 21-day cycle. Participants will receive cisplatin intravenously followed by gemcitabine on Days 1 and 8 of each 21-day cycle for Cycles 1-8.
Receives: Drug: Atezolizumab; Drug: Bevacizumab; Drug: Cisplatin; Drug: Gemcitabine
Arm B: Atezo+PBO+CisGem, followed by Atezo+PBOActive comparatorParticipants will receive atezolizumab intravenously on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, and clinical status. Participants will receive placebo matching bevacizumab intravenously on Day 1 of each 21-day cycle. Participants will receive cisplatin intravenously followed by gemcitabine on Days 1 and 8 of each 21-day cycle for Cycles 1-8.
Receives: Drug: Atezolizumab; Other: Placebo; Drug: Cisplatin; Drug: Gemcitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival (PFS)

    PFS is defined as the time from randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first)

    Measured: Randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first)(up to approximately 14 months)

Secondary outcomes (9)

  1. Overall Survival (OS)

    OS is defined as the time from randomization to death from any cause.

    Measured: Randomization to death from any cause (up to approximately 23 months)

  2. Confirmed Objective Response Rate (ORR)

    Confirmed ORR is defined as the proportion of participants with Complete Response (CR) or Partial Response (PR) on two consecutive occasions >=4 weeks apart, as determined by the investigator according to RECIST v1.1.

    Measured: Randomization up to approximately 14 months

  3. Duration of Response (DOR)

    DOR is defined as the time from the first occurrence of a confirmed objective response to disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first).

    Measured: First occurrence of a confirmed objective response to disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first)(up to approximately 14 months)

  4. Disease Control Rate (DCR)

    DCR is defined as the proportion of participants with a CR or a PR on two consecutive occasions >= 4 weeks apart or SD with a minimum duration of 9weeks, as determined by the investigator according to RECIST v1.1

    Measured: Randomization up to approximately 14 months

  5. Time to Confirmed Deterioration (TTCD)

    TTCD in patient-reported physical functioning, role functioning, and quality of life, as measured by the respective scales of the EORTC QLQ-C30 and/or EORTC IL77, and defined as the time from randomization to the first clinically meaningful deterioration that is either maintained for two consecutive assessments or followed by death from any cause within 3 weeks.

    Measured: Randomization to the first clinically meaningful deterioration (up to approximately 14 months)

  6. Percentage of Participants With at Least One Adverse Event

    Percentage of participants with at least one adverse event.

    Measured: Treatment start up to approximately 30 months.

  7. Serum Concentration of Atezolizumab

    Serum concentration of atezolizumab at specified timepoints.

    Measured: Pre-Dose on Day 1 of Cycles 1, 2, 3, 4, 8, 12, and 16, and Post Dose Day 1 of Cycle 1 (cycle length=21 days)

  8. Prevalence of ADAs to Atezolizumab

    Measured: Baseline

  9. Incidence of ADAs to Atezolizumab

    Measured: At pre-defined intervals from administration of study drug up to approximately 14 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Dec 2020
  2. Study start23 Feb 2021
  3. Primary completion16 May 2022
  4. Study completion25 Aug 2023

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
162 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04677504
Sponsor's protocol ID
GO42661
Status last verified
Jun 2024
First submitted
16 Dec 2020
Last updated
3 Jul 2024
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here ( https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).

Publications

  • Macarulla T, Ren Z, Chon HJ, Park JO, Kim JW, Pressiani T, Li D, Zhukova L, Zhu AX, Chen MH, Hack SP, Wu S, Liu B, Guan X, Lu S, Wang Y, El-Khoueiry AB. Atezolizumab Plus Chemotherapy With or Without Bevacizumab in Advanced Biliary Tract Cancer: Clinical and Biomarker Data From the Randomized Phase II IMbrave151 Trial. J Clin Oncol. 2025 Feb 10;43(5):545-557. doi: 10.1200/JCO.24.00337. Epub 2024 Oct 18.

    PubMed 39423355

  • Hack SP, Verret W, Mulla S, Liu B, Wang Y, Macarulla T, Ren Z, El-Khoueiry AB, Zhu AX. IMbrave 151: a randomized phase II trial of atezolizumab combined with bevacizumab and chemotherapy in patients with advanced biliary tract cancer. Ther Adv Med Oncol. 2021 Jul 31;13:17588359211036544. doi: 10.1177/17588359211036544. eCollection 2021.

    PubMed 34377158

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Atezolizumab, Bevacizumab and Cisplatin in people with Biliary Tract Cancer, run by Hoffmann-La Roche at 49 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 49 sites in United States, Poland, South Korea, Spain, Italy and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) (time frame: Randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first)(up to approximately 14 months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04677504, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2024.

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