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

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04677504
Collaborator
(none)
162
Enrollment
50
Locations
2
Arms
26
Anticipated Duration (Months)
3.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
162 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Feb 23, 2021
Anticipated Primary Completion Date :
Feb 21, 2023
Anticipated Study Completion Date :
Apr 24, 2023

Arms and Interventions

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

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

    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.

    Outcome Measures

    Primary Outcome Measures

    1. Progression Free Survival (PFS) [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 approximatly 3-5 years)]

      PFS, 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)

    Secondary Outcome Measures

    1. Overall Survival (OS) [Randomization to death from any cause (up to approximately 3-5 years)]

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

    2. Confirmed Objective Response Rate (ORR) [Randomization up to approximately 3-5 years]

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

    3. Duration of Response (DOR) [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 3-5 years)]

      DOR, 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).

    4. Disease Control Rate (DCR) [Randomization up to approximately 3-5 years]

      DCR, defined as the proportion of patients 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

    5. Time to Confirmed Deterioration (TTCD) [Randomization to the first clinically meaningful deterioration (up to approximately 3-5 years)]

      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.

    6. Percentage of Participants With Adverse Events [Randomization up to approximately 3-5 years]

    7. Serum Concentration of atezolizumab [At pre-defined intervals from administration of study drug up to approximately 3-5 years]

      Serum concentration of atezolizumab at specified timepoints.

    8. Prevalence of ADAs to Atezolizumab [Baseline]

    9. Incidence of ADAs to Atezolizumab [At pre-defined intervals from administration of study drug up to approximately 3-5 years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope Cancer Center Duarte California United States 91010
    2 Massachusetts General Hospital Boston Massachusetts United States 02114
    3 Duke Cancer Center Durham North Carolina United States 27710
    4 SCRI-Tennessee Oncology Nashville Tennessee United States 37203
    5 University of Virginia Charlottesville Virginia United States 22903
    6 Nanfang Hospital, Southern Medical University Guangzhou China 510515
    7 Sir Run Run Shaw Hospital Zhejiang University Hangzhou City China 310016
    8 Nan Tong Tumor Hospital Nantong City China 226361
    9 Zhongshan Hospital Fudan University Shanghai China 200032
    10 Queen Mary Hospital; Dept. Of Haematology & Oncology Hong Kong Hong Kong
    11 Prince of Wales Hosp; Dept. Of Clinical Onc Shatin Hong Kong
    12 Fondazione Pascale; U.O. Sperimentazioni Cliniche Napoli Campania Italy 80100
    13 Azienda Ospedaliero Universitaria di Bologna; Istituto di Ematologia "Lorenzo e Ariosto Seragnoli" Bologna Emilia-Romagna Italy 40139
    14 Istituto Clinico Humanitas - Humanitas Cancer Center Rozzano Sicilia Italy 20089
    15 IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II Padova Veneto Italy 35128
    16 CHA Bundang Medical Center Gyeonggi-do Korea, Republic of 13496
    17 Seoul National University Bundang Hospital Seongnam-si Korea, Republic of 13605
    18 Seoul National University Hospital Seoul Korea, Republic of 03080
    19 Asan Medical Center Seoul Korea, Republic of 05505
    20 Samsung Medical Center Seoul Korea, Republic of 06351
    21 SP ZOZ Wojewódzki Szpital Specjalistyczny nr 4; Oddzial Onkologii Klinicznej Bytom Poland 41-902
    22 Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii Gdańsk Poland 80-214
    23 Szpital Wojewódzki im. Mikołaja Kopernika; Oddział Dzienny Chemioterapii Koszalin Poland 75-581
    24 NIO im Marii Sklodowskiej-Curie; Klinika Onkologii i Radioterapii Warszawa Poland 02-034
    25 Dolnośląskie Centrum Onkologii; Oddział Onkologii Klinicznej i Chemioterapii Wrocław Poland 53-413
    26 SBIH "Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM" Moskva Moskovskaja Oblast Russian Federation 111123
    27 FSBI "National Medical Research Center of Oncology N.N. Blokhin" Moscow Russian Federation 115478
    28 First Moscow State Medical University n.a. I.M. Sechenov Moscow Russian Federation 119991
    29 GBUZ Saint Petersburg Clinical Research Center of Specialized Types of Care (Oncology) Saint Petersburg Russian Federation 197758
    30 Complejo Hospitalario de Navarra; Servicio de Oncologia Pamplona Navarra Spain 31008
    31 Hospital Universitari Vall d'Hebron; Oncology Barcelona Spain 08035
    32 Hospital Ramon y Cajal; Servicio de Oncologia Madrid Spain 28034
    33 Complejo Hospitalario de Orense; Servicio de Oncologia Orense Spain 32005
    34 Hospital Universitario Miguel Servet; Servicio Oncologia Zaragoza Spain 50009
    35 Taipei Veterans General Hospital; Department of Oncology Taipei City Taiwan 112201
    36 National Taiwan Uni Hospital; Dept of Oncology Taipei Taiwan 100
    37 Maharaj Nakorn Chiang Mai Hosp; Oncology Unit Chiangmai Thailand 50200
    38 Srinagarind Hospital; Medical Oncology Unit Khon Kaen Thailand 40002
    39 Sunpasitthiprasong Hospital; Oncology and/or Hematology Ubon Ratchathani Thailand 34000
    40 Adana Acıbadem Hospital Oncology Department Adana Turkey 01130
    41 Memorial Ankara Hastanesi Ankara Turkey 06520
    42 Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department Malatya Turkey 44280
    43 Koc Universitesi Hastanesi; Tıbbi Onkoloji Zeyti̇nburnu Turkey 34010
    44 SI Institute of general&urgent surgery n/a Zaytseva V.T NAMSU Kharkiv Kharkiv Governorate Ukraine 61018
    45 Kharkov Regional Oncology Center Kharkiv Kharkiv Governorate Ukraine 61070
    46 SI "Shalimov National Institute of Surgery and Transplantation" of Nat.Acad of Med.Sci of Ukraine Kyiv KIEV Governorate Ukraine 03126
    47 Beatson West of Scotland Cancer Centre Glasgow United Kingdom G12 0YN
    48 Royal Free Hospital London United Kingdom NW3 2QS
    49 Churchill Hospital Oxford United Kingdom OX3 7LJ
    50 Royal Marsden Hospital (Sutton) Sutton United Kingdom SM2 5PT

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT04677504
    Other Study ID Numbers:
    • GO42661
    First Posted:
    Dec 21, 2020
    Last Update Posted:
    Jul 6, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Biliary Tract Neoplasms
    Gemcitabine
    Bevacizumab
    Atezolizumab

    Study Results

    No Results Posted as of Jul 6, 2022