Clinical trial NCT04677504: A Study of Atezolizumab With or Without Bevacizumab in Combination With Cisplatin Plus Gemcitabine in Patients With Untreated, Advanced Biliary Tract Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Biliary Tract Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-12-21
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 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:
measure: Overall Survival (OS)
timeFrame: Randomization to death from any cause (up to approximately 23 months)
measure: Confirmed Objective Response Rate (ORR)
timeFrame: Randomization up to approximately 14 months
measure: Duration of Response (DOR)
timeFrame: 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)
measure: Disease Control Rate (DCR)
timeFrame: Randomization up to approximately 14 months
measure: Time to Confirmed Deterioration (TTCD)
timeFrame: Randomization to the first clinically meaningful deterioration (up to approximately 14 months)
measure: Percentage of Participants With at Least One Adverse Event
timeFrame: Treatment start up to approximately 30 months.
measure: Serum Concentration of Atezolizumab
timeFrame: 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)
measure: Prevalence of ADAs to Atezolizumab
timeFrame: Baseline
measure: Incidence of ADAs to Atezolizumab
timeFrame: At pre-defined intervals from administration of study drug up to approximately 14 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Cancer Center
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
city: Nashville
country: United States
facility: Sarah Cannon Research Institute / Tennessee Oncology
state: Tennessee
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
city: Hangzhou City
country: China
facility: Sir Run Run Shaw Hospital Zhejiang University
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital; Dept. Of Haematology & Oncology
city: Shatin
country: Hong Kong
facility: Prince of Wales Hosp; Dept. Of Clinical Onc
city: Napoli
country: Italy
facility: Fondazione Pascale; U.O. Sperimentazioni Cliniche
state: Campania
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria di Bologna; Istituto di Ematologia "Lorenzo e Ariosto Seragnoli"
state: Emilia-Romagna
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas - Humanitas Cancer Center
state: Sicilia
city: Padova
country: Italy
facility: IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II
state: Veneto
city: Gyeonggi-do
country: Korea, Republic of
facility: CHA Bundang Medical Center
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Bytom
country: Poland
facility: SP ZOZ Wojewódzki Szpital Specjalistyczny nr 4; Oddzial Onkologii Klinicznej
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii
city: Koszalin
country: Poland
facility: Szpital Wojewódzki im. Miko?aja Kopernika; Oddzia? Dzienny Chemioterapii
city: Warszawa
country: Poland
facility: NIO im Marii Sklodowskiej-Curie; Klinika Onkologii i Radioterapii
city: Wroc?aw
country: Poland
facility: Dolno?l?skie Centrum Onkologii; Oddzia? Onkologii Klinicznej i Chemioterapii
city: Moscow
country: Russian Federation
facility: FSBI "National Medical Research Center of Oncology N.N. Blokhin?
state: Moskovskaja Oblast
city: Moscow
country: Russian Federation
facility: First Moscow State Medical University n.a. I.M. Sechenov
state: Moskovskaja Oblast
city: Moskva
country: Russian Federation
facility: SBIH "Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM"
state: Moskovskaja Oblast
city: Saint Petersburg
country: Russian Federation
facility: GBUZ Saint Petersburg Clinical Research Center of Specialized Types of Care (Oncology)
state: Sankt Petersburg
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra; Servicio de Oncologia
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron; Oncology
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal; Servicio de Oncologia
city: Orense
country: Spain
facility: Complejo Hospitalario de Orense; Servicio de Oncologia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet; Servicio Oncologia
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital; Department of Oncology
city: Taipei
country: Taiwan
facility: National Taiwan Uni Hospital; Dept of Oncology
city: Chiangmai
country: Thailand
facility: Maharaj Nakorn Chiang Mai Hosp; Oncology Unit
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital; Medical Oncology Unit
city: Ubon Ratchathani
country: Thailand
facility: Sunpasitthiprasong Hospital; Oncology and/or Hematology
city: Adana
country: Turkey
facility: Adana Ac?badem Hospital Oncology Department
city: Ankara
country: Turkey
facility: Memorial Ankara Hastanesi
city: Malatya
country: Turkey
facility: Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department
city: Zeyt?nburnu
country: Turkey
facility: Koc Universitesi Hastanesi; T?bbi Onkoloji
city: Kharkiv
country: Ukraine
facility: SI Institute of general&urgent surgery n/a Zaytseva V.T NAMSU
state: Kharkiv Governorate
city: Kharkiv
country: Ukraine
facility: ?Kharkov Regional Oncology Center
state: Kharkiv Governorate
city: Kyiv
country: Ukraine
facility: SI "Shalimov National Institute of Surgery and Transplantation" of Nat.Acad of Med.Sci of Ukraine
state: KIEV Governorate
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: Royal Free Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital (Sutton)
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.