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

NCT ID: NCT04677504

Last Updated: 2024-07-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 162 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-23
• Study Completion Date: 2023-08-25

Brief 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. Treatment will consist of a chemotherapy combination phase followed by a cancer immunotherapy (CIT)/placebo phase.

Conditions

Biliary Tract Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Arm A: Atezo+Bev+CisGem, followed by Atezo+Bev

Participants 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.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

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

Bevacizumab

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

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.

Gemcitabine

Intervention Type: DRUG

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.

Arm B: Atezo+PBO+CisGem, followed by Atezo+PBO

Participants 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.

Group Type: ACTIVE_COMPARATOR

Atezolizumab

Intervention Type: DRUG

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

Placebo

Intervention Type: OTHER

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

Cisplatin

Intervention Type: DRUG

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.

Gemcitabine

Intervention Type: DRUG

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.

Interventions

Atezolizumab

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

Intervention Type: DRUG

Bevacizumab

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

Intervention Type: DRUG

Placebo

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

Intervention Type: OTHER

Cisplatin

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.

Intervention Type: DRUG

Gemcitabine

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.

Intervention Type: DRUG

Other Intervention Names

Tecentriq; Avastin

Eligibility Criteria

Inclusion Criteria

• 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
• 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

Exclusion Criteria

• 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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

City of Hope Cancer Center

Duarte, California, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Duke Cancer Center

Durham, North Carolina, United States

Sarah Cannon Research Institute / Tennessee Oncology

Nashville, Tennessee, United States

University of Virginia

Charlottesville, Virginia, United States

Nanfang Hospital, Southern Medical University

Guangzhou, , China

Sir Run Run Shaw Hospital Zhejiang University

Hangzhou, , China

Zhongshan Hospital Fudan University

Shanghai, , China

Queen Mary Hospital; Dept. Of Haematology & Oncology

Hong Kong, , Hong Kong

Prince of Wales Hosp; Dept. Of Clinical Onc

Shatin, , Hong Kong

Fondazione Pascale; U.O. Sperimentazioni Cliniche

Napoli, Campania, Italy

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

Bologna, Emilia-Romagna, Italy

Istituto Clinico Humanitas - Humanitas Cancer Center

Rozzano, Sicily, Italy

IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II

Padua, Veneto, Italy

SP ZOZ Wojewódzki Szpital Specjalistyczny nr 4; Oddzial Onkologii Klinicznej

Bytom, , Poland

Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii

Gdansk, , Poland

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

Koszalin, , Poland

NIO im Marii Sklodowskiej-Curie; Klinika Onkologii i Radioterapii

Warsaw, , Poland

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

Wroc?aw, , Poland

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

Moscow, Moscow Oblast, Russia

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

Moscow, Moscow Oblast, Russia

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

Moskva, Moscow Oblast, Russia

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

Saint Petersburg, Sankt-Peterburg, Russia

CHA Bundang Medical Center

Gyeonggi-do, , South Korea

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Complejo Hospitalario de Navarra; Servicio de Oncologia

Pamplona, Navarre, Spain

Hospital Universitari Vall d'Hebron; Oncology

Barcelona, , Spain

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, , Spain

Complejo Hospitalario de Orense; Servicio de Oncologia

Ourense, , Spain

Hospital Universitario Miguel Servet; Servicio Oncologia

Zaragoza, , Spain

National Taiwan Uni Hospital; Dept of Oncology

Taipei, , Taiwan

Taipei Veterans General Hospital; Department of Oncology

Taipei, , Taiwan

Maharaj Nakorn Chiang Mai Hosp; Oncology Unit

Chiang Mai, , Thailand

Srinagarind Hospital; Medical Oncology Unit

Khon Kaen, , Thailand

Sunpasitthiprasong Hospital; Oncology and/or Hematology

Ubon Ratchathani, , Thailand

Adana Ac?badem Hospital Oncology Department

Adana, , Turkey (Türkiye)

Memorial Ankara Hastanesi

Ankara, , Turkey (Türkiye)

Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department

Malatya, , Turkey (Türkiye)

Koc Universitesi Hastanesi; T?bbi Onkoloji

Zeyt?nburnu, , Turkey (Türkiye)

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

Kharkiv, Kharkiv Governorate, Ukraine

?Kharkov Regional Oncology Center

Kharkiv, Kharkiv Governorate, Ukraine

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

Kyiv, KIEV Governorate, Ukraine

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Royal Free Hospital

London, , United Kingdom

Churchill Hospital

Oxford, , United Kingdom

Royal Marsden Hospital (Sutton)

Sutton, , United Kingdom

Countries

United States; China; Hong Kong; Italy; Poland; Russia; South Korea; Spain; Taiwan; Thailand; Turkey (Türkiye); Ukraine; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 39423355 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34377158 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

GO42661

Identifier Type: -

Identifier Source: org_study_id