A Study of Atezolizumab With or Without Bevacizumab in Combination With Cisplatin Plus Gemcitabine in Patients With Untreated, Advanced Biliary Tract Cancer
- Conditions
- Biliary Tract Cancer
- Interventions
- Registration Number
- NCT04677504
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 162
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Atezo+Bev+CisGem, followed by Atezo+Bev Gemcitabine 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. Arm B: Atezo+PBO+CisGem, followed by Atezo+PBO Placebo 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. Arm A: Atezo+Bev+CisGem, followed by Atezo+Bev Atezolizumab 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. Arm A: Atezo+Bev+CisGem, followed by Atezo+Bev Bevacizumab 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. Arm A: Atezo+Bev+CisGem, followed by Atezo+Bev Cisplatin 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. Arm B: Atezo+PBO+CisGem, followed by Atezo+PBO Atezolizumab 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. Arm B: Atezo+PBO+CisGem, followed by Atezo+PBO Cisplatin 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. Arm B: Atezo+PBO+CisGem, followed by Atezo+PBO Gemcitabine 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.
- Primary Outcome Measures
Name Time Method 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 approximately 14 months) 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)
- Secondary Outcome Measures
Name Time Method 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 14 months) 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).
Overall Survival (OS) Randomization to death from any cause (up to approximately 23 months) OS is defined as the time from randomization to death from any cause.
Time to Confirmed Deterioration (TTCD) Randomization to the first clinically meaningful deterioration (up to approximately 14 months) 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.
Percentage of Participants With at Least One Adverse Event Treatment start up to approximately 30 months. Percentage of participants with at least one adverse event.
Incidence of ADAs to Atezolizumab At pre-defined intervals from administration of study drug up to approximately 14 months Confirmed Objective Response Rate (ORR) Randomization up to approximately 14 months 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.
Disease Control Rate (DCR) Randomization up to approximately 14 months 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
Prevalence of ADAs to Atezolizumab Baseline Serum Concentration of Atezolizumab 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) Serum concentration of atezolizumab at specified timepoints.
Trial Locations
- Locations (49)
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Duke Cancer Center
🇺🇸Durham, North Carolina, United States
City of Hope Cancer Center
🇺🇸Duarte, California, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Nanfang Hospital, Southern Medical University
🇨🇳Guangzhou, China
Zhongshan Hospital Fudan University
🇨🇳Shanghai, China
IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II
🇮🇹Padova, Veneto, Italy
CHA Bundang Medical Center
🇰🇷Gyeonggi-do, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii
🇵🇱Gdansk, Poland
First Moscow State Medical University n.a. I.M. Sechenov
🇷🇺Moscow, Moskovskaja Oblast, Russian Federation
FSBI "National Medical Research Center of Oncology N.N. Blokhin?
🇷🇺Moscow, Moskovskaja Oblast, Russian Federation
SBIH "Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM"
🇷🇺Moskva, Moskovskaja Oblast, Russian Federation
Complejo Hospitalario de Navarra; Servicio de Oncologia
🇪🇸Pamplona, Navarra, Spain
Complejo Hospitalario de Orense; Servicio de Oncologia
🇪🇸Orense, Spain
Hospital Universitari Vall d'Hebron; Oncology
🇪🇸Barcelona, Spain
Hospital Universitario Miguel Servet; Servicio Oncologia
🇪🇸Zaragoza, Spain
Sir Run Run Shaw Hospital Zhejiang University
🇨🇳Hangzhou City, China
Maharaj Nakorn Chiang Mai Hosp; Oncology Unit
🇹🇭Chiangmai, Thailand
National Taiwan Uni Hospital; Dept of Oncology
🇨🇳Taipei, Taiwan
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
Memorial Ankara Hastanesi
🇹🇷Ankara, Turkey
Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department
🇹🇷Malatya, Turkey
Koc Universitesi Hastanesi; T?bbi Onkoloji
🇹🇷Zeyt?nburnu, Turkey
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 Marsden Hospital (Sutton)
🇬🇧Sutton, United Kingdom
Royal Free Hospital
🇬🇧London, United Kingdom
Churchill Hospital
🇬🇧Oxford, United Kingdom
Sarah Cannon Research Institute / Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
NIO im Marii Sklodowskiej-Curie; Klinika Onkologii i Radioterapii
🇵🇱Warszawa, Poland
Taipei Veterans General Hospital; Department of Oncology
🇨🇳Taipei City, Taiwan
Szpital Wojewódzki im. Miko?aja Kopernika; Oddzia? Dzienny Chemioterapii
🇵🇱Koszalin, Poland
SP ZOZ Wojewódzki Szpital Specjalistyczny nr 4; Oddzial Onkologii Klinicznej
🇵🇱Bytom, Poland
Dolno?l?skie Centrum Onkologii; Oddzia? Onkologii Klinicznej i Chemioterapii
🇵🇱Wroc?aw, Poland
GBUZ Saint Petersburg Clinical Research Center of Specialized Types of Care (Oncology)
🇷🇺Saint Petersburg, Sankt Petersburg, Russian Federation
SI Institute of general&urgent surgery n/a Zaytseva V.T NAMSU
🇺🇦Kharkiv, Kharkiv Governorate, Ukraine
?Kharkov Regional Oncology Center
🇺🇦Kharkiv, Kharkiv Governorate, Ukraine
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, Sicilia, Italy
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Ramon y Cajal; Servicio de Oncologia
🇪🇸Madrid, Spain
Queen Mary Hospital; Dept. Of Haematology & Oncology
🇭🇰Hong Kong, Hong Kong
Prince of Wales Hosp; Dept. Of Clinical Onc
🇭🇰Shatin, Hong Kong