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

Biliary Tract Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04677504
• Other study ID #: GO42661
• Status: Completed
• Phase: Phase 2
• Start date: February 23, 2021
• Est. completion date: August 25, 2023

Study information

• Verified date: October 2023
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 162
• Est. completion date: August 25, 2023
• Est. primary completion date: May 16, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Biliary Tract Cancer
• Biliary Tract Neoplasms

Intervention

Drug:
• Atezolizumab
Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.
• Bevacizumab
Bevacizumab will be administered at a dose of 15 mg/kg intravenously on Day 1 of each 21-day cycle after atezolizumab.

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.
• 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.

Locations

Country	Name	City	State
China	Nanfang Hospital, Southern Medical University	Guangzhou
China	Sir Run Run Shaw Hospital Zhejiang University	Hangzhou City
China	Zhongshan Hospital Fudan University	Shanghai
Hong Kong	Queen Mary Hospital; Dept. Of Haematology & Oncology	Hong Kong
Hong Kong	Prince of Wales Hosp; Dept. Of Clinical Onc	Shatin
Italy	Azienda Ospedaliero Universitaria di Bologna; Istituto di Ematologia "Lorenzo e Ariosto Seragnoli"	Bologna	Emilia-Romagna
Italy	Fondazione Pascale; U.O. Sperimentazioni Cliniche	Napoli	Campania
Italy	IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II	Padova	Veneto
Italy	Istituto Clinico Humanitas - Humanitas Cancer Center	Rozzano	Sicilia
Korea, Republic of	CHA Bundang Medical Center	Gyeonggi-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Poland	SP ZOZ Wojewódzki Szpital Specjalistyczny nr 4; Oddzial Onkologii Klinicznej	Bytom
Poland	Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii	Gda?sk
Poland	Szpital Wojewódzki im. Miko?aja Kopernika; Oddzia? Dzienny Chemioterapii	Koszalin
Poland	NIO im Marii Sklodowskiej-Curie; Klinika Onkologii i Radioterapii	Warszawa
Poland	Dolno?l?skie Centrum Onkologii; Oddzia? Onkologii Klinicznej i Chemioterapii	Wroc?aw
Russian Federation	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	GBUZ Saint Petersburg Clinical Research Center of Specialized Types of Care (Oncology)	Saint Petersburg	Sankt Petersburg
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	Orense
Spain	Complejo Hospitalario de Navarra; Servicio de Oncologia	Pamplona	Navarra
Spain	Hospital Universitario Miguel Servet; Servicio Oncologia	Zaragoza
Taiwan	National Taiwan Uni Hospital; Dept of Oncology	Taipei
Taiwan	Taipei Veterans General Hospital; Department of Oncology	Taipei City
Thailand	Maharaj Nakorn Chiang Mai Hosp; Oncology Unit	Chiangmai
Thailand	Srinagarind Hospital; Medical Oncology Unit	Khon Kaen
Thailand	Sunpasitthiprasong Hospital; Oncology and/or Hematology	Ubon Ratchathani
Turkey	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
Ukraine	?Kharkov Regional Oncology Center	Kharkiv	Kharkiv Governorate
Ukraine	SI Institute of general&urgent surgery n/a Zaytseva V.T NAMSU	Kharkiv	Kharkiv Governorate
Ukraine	SI "Shalimov National Institute of Surgery and Transplantation" of Nat.Acad of Med.Sci of Ukraine	Kyiv	KIEV Governorate
United Kingdom	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 States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Virginia	Charlottesville	Virginia
United States	City of Hope Cancer Center	Duarte	California
United States	Duke Cancer Center	Durham	North Carolina
United States	SCRI-Tennessee Oncology	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  China,  Hong Kong,  Italy,  Korea, Republic of,  Poland,  Russian Federation,  Spain,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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 3-5 years)
Secondary	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
Secondary	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)
Secondary	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
Secondary	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)
Secondary	Percentage of Participants With Adverse Events		Randomization up to approximately 3-5 years
Secondary	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)
Secondary	Prevalence of ADAs to Atezolizumab		Baseline
Secondary	Incidence of ADAs to Atezolizumab		At pre-defined intervals from administration of study drug up to approximately 14 months