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

Roche

Status and phase: Completed; Phase 2

Conditions: Biliary Tract Cancer

Treatments: Drug: Atezolizumab; Drug: Bevacizumab; Drug: Gemcitabine; Other: Placebo; Drug: Cisplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT04677504

GO42661

Details and patient eligibility

About

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.

Enrollment: 162 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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162 participants in 2 patient groups

Arm A: Atezo+Bev+CisGem, followed by Atezo+Bev

Experimental group

Description:

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.

Treatment:

Drug: Cisplatin

Drug: Gemcitabine

Drug: Bevacizumab

Drug: Atezolizumab

Arm B: Atezo+PBO+CisGem, followed by Atezo+PBO

Active Comparator group

Description:

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.

Treatment:

Drug: Cisplatin

Other: Placebo

Drug: Gemcitabine

Drug: Atezolizumab