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

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.

Study Overview

• Status: Completed
• Conditions: Biliary Tract Cancer
• Intervention / Treatment: Drug: Atezolizumab; Drug: Bevacizumab; Drug: Cisplatin; Drug: Gemcitabine; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 162
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangzhou, China, 510515
    • Nanfang Hospital, Southern Medical University
  • Hangzhou City, China, 310016
    • Sir Run Run Shaw Hospital Zhejiang University
  • Shanghai, China, 200032
    • Zhongshan Hospital Fudan University
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital; Dept. Of Haematology & Oncology
  • Shatin, Hong Kong
    • Prince of Wales Hosp; Dept. Of Clinical Onc
• Italy
  • Campania
    • Napoli, Campania, Italy, 80100
      • Fondazione Pascale; U.O. Sperimentazioni Cliniche
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40139
      • Azienda Ospedaliero Universitaria di Bologna; Istituto di Ematologia "Lorenzo e Ariosto Seragnoli"
  • Sicilia
    • Rozzano, Sicilia, Italy, 20089
      • Istituto Clinico Humanitas - Humanitas Cancer Center
  • Veneto
    • Padova, Veneto, Italy, 35128
      • IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of, 13496
    • CHA Bundang Medical Center
  • Seongnam-si, Korea, Republic of, 463-707
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
• Poland
  • Bytom, Poland, 41-902
    • SP ZOZ Wojewódzki Szpital Specjalistyczny nr 4; Oddzial Onkologii Klinicznej
  • Gdansk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii
  • Koszalin, Poland, 75-581
    • Szpital Wojewódzki im. Miko?aja Kopernika; Oddzia? Dzienny Chemioterapii
  • Warszawa, Poland, 02-034
    • NIO im Marii Sklodowskiej-Curie; Klinika Onkologii i Radioterapii
  • Wroc?aw, Poland, 53-413
    • Dolno?l?skie Centrum Onkologii; Oddzia? Onkologii Klinicznej i Chemioterapii
• Russian Federation
  • Moskovskaja Oblast
    • Moscow, Moskovskaja Oblast, Russian Federation, 115478
      • FSBI "National Medical Research Center of Oncology N.N. Blokhin?
    • Moscow, Moskovskaja Oblast, Russian Federation, 119991
      • First Moscow State Medical University n.a. I.M. Sechenov
    • Moskva, Moskovskaja Oblast, Russian Federation, 111123
      • SBIH "Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM"
  • Sankt Petersburg
    • Saint Petersburg, Sankt Petersburg, Russian Federation, 197758
      • GBUZ Saint Petersburg Clinical Research Center of Specialized Types of Care (Oncology)
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron; Oncology
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal; Servicio de Oncologia
  • Orense, Spain, 32005
    • Complejo Hospitalario de Orense; Servicio de Oncologia
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet; Servicio Oncologia
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Complejo Hospitalario de Navarra; Servicio de Oncologia
• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan Uni Hospital; Dept of Oncology
  • Taipei City, Taiwan, 112201
    • Taipei Veterans General Hospital; Department of Oncology
• Thailand
  • Chiangmai, Thailand, 50200
    • Maharaj Nakorn Chiang Mai Hosp; Oncology Unit
  • Khon Kaen, Thailand, 40002
    • Srinagarind Hospital; Medical Oncology Unit
  • Ubon Ratchathani, Thailand, 34000
    • Sunpasitthiprasong Hospital; Oncology and/or Hematology
• Turkey
  • Adana, Turkey, 01130
    • Adana Ac?badem Hospital Oncology Department
  • Ankara, Turkey, 06520
    • Memorial Ankara Hastanesi
  • Malatya, Turkey, 44280
    • Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department
  • Zeyt?nburnu, Turkey, 34010
    • Koc Universitesi Hastanesi; T?bbi Onkoloji
• Ukraine
  • KIEV Governorate
    • Kyiv, KIEV Governorate, Ukraine, 03126
      • SI "Shalimov National Institute of Surgery and Transplantation" of Nat.Acad of Med.Sci of Ukraine
  • Kharkiv Governorate
    • Kharkiv, Kharkiv Governorate, Ukraine, 61018
      • SI Institute of general&urgent surgery n/a Zaytseva V.T NAMSU
    • Kharkiv, Kharkiv Governorate, Ukraine, 61070
      • ?Kharkov Regional Oncology Center
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre
  • London, United Kingdom, NW3 2QS
    • Royal Free Hospital
  • Oxford, United Kingdom, OX3 7LJ
    • Churchill Hospital
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital (Sutton)
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute / Tennessee Oncology
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Atezolizumab; Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.; Other Names: Tecentriq; Drug: Bevacizumab; Bevacizumab will be administered at a dose of 15 mg/kg intravenously on Day 1 of each 21-day cycle after atezolizumab.; Other Names: Avastin; Drug: 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.; 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.
Active Comparator: 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.	Drug: Atezolizumab; Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.; Other Names: Tecentriq; Drug: 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.; 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.; Other: Placebo; Placebo matching bevacizumab will be administered intravenously on Day 1 of each 21-day cycle after atezolizumab.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of ADAs to Atezolizumab		Baseline
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.	Randomization up to approximately 14 months
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).	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)
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	Randomization up to approximately 14 months
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.	Randomization to the first clinically meaningful deterioration (up to approximately 14 months)
Serum Concentration of Atezolizumab	Serum concentration of atezolizumab at specified timepoints.	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)
Incidence of ADAs to Atezolizumab		At pre-defined intervals from administration of study drug up to approximately 14 months
Overall Survival (OS)	OS is defined as the time from randomization to death from any cause.	Randomization to death from any cause (up to approximately 23 months)
Percentage of Participants With at Least One Adverse Event	Percentage of participants with at least one adverse event.	Treatment start up to approximately 30 months.

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2021
• Primary Completion (Actual): May 16, 2022
• Study Completion (Actual): August 25, 2023

Study Registration Dates

• First Submitted: December 16, 2020
• First Submitted That Met QC Criteria: December 16, 2020
• First Posted (Actual): December 21, 2020

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: June 11, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Biliary Tract Diseases; Biliary Tract Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Immune Checkpoint Inhibitors; Bevacizumab; Atezolizumab; Gemcitabine
• Other Study ID Numbers: GO42661

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No