A Study of Atezolizumab With or Without Bevacizumab in Combination With Cisplatin Plus Gemcitabine in Patients With Untreated, Advanced Biliary Tract Cancer
Condition: Biliary Tract Cancer
MeSH terms: Biliary Tract Neoplasms
Intervention: Atezolizumab; Bevacizumab; Placebo; Cisplatin; Gemcitabine
Intervention description: Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.; Bevacizumab will be administered at a dose of 15 mg/kg intravenously on Day 1 of each 21-day cycle after atezolizumab.; Placebo matching bevacizumab will be administered intravenously on Day 1 of each 21-day cycle after atezolizumab.; 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 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.
Intervention MeSH terms: Bevacizumab; Atezolizumab; Gemcitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 162.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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