Biliary tract cancer MedDRA version: 20.0 Level: PT Classification code 10008593 Term: Cholangiocarcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10001141 Term: Adenocarcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
F. Hoffman-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Age >= 18 years at the time of signing Informed Consent Form •Ability to comply with the study protocol •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 intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder cancer •No prior systemic therapy (including systemic investigational agents) for advanced biliary tract cancer •At least one measurable untreated lesion (per RECIST v1.1) •Adequate biliary drainage with no evidence of ongoing infection •Availability of a representative tumor specimen that is suitable for determination of PD-L1 status via central testing •Negative HIV test at screening with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count >= 200/?L, and have an undetectable viral load •Documented virology status of hepatitis, as confirmed by screening hepatitis B virus (HBV) and hepatitis C virus (HCV) tests •Eastern Cooperative Oncology Group (ECOG) 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 while they are receiving atezolizumab and bevacizumab and for 5 months after the final dose of atezolizumab and for 6 months after the final dose of bevacizumab, cisplatin or gemcitabine, whichever is later •For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm during the treatment period and for 6 months after the final dose of bevacizumab, cisplatin or gemcitabine, whichever is later, to avoid exposing the embryo Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 75 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 75
Exclusion criteria
Exclusion criteria: •Recurrent disease == 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 •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 CT scan •Significant cardiovascular disease within 3 months prior to Day 1 of Cycle 1, unstable arrhythmia, or unstable angina •History of malignancy other than BTC within 5 years prior to screening •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 •Severe infection within 4 weeks prior to Day 1 of Cycle 1 •Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to Day 1 of Cycle 1 •Prior allogeneic stem cell or solid organ transplantation •On the waiting list for liver transplantation •Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications •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 •Co-infection with HBV and HCV •Uncontrolled or symptomatic hypercalcemia •History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins •History of allergic reactions to cisplatin or other platinum-containing compounds •Known hypersensitivity to gemcitabine •Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or bevacizumab formulations •Treatment with a live, attenuated vaccine within 4 weeks prior to Day 1 of Cycle 1 or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab •Treatment with investigational therapy within 4 weeks prior to Day 1 of Cycle 1 •Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies •Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to Day 1 of Cycle 1 •Treatment with systemic immunosuppressive medication within 2 weeks prior to Day 1 of Cycle 1 or anticipation of need for systemic immunosuppressive medication during study treatment •Inadequately controlled arterial hypertension (defined as systolic blood pressure [BP] ? 150 mmHg and/or diastolic BP ? 100 mmHg), based on an average of at least three BP readings at two or more sessions •History of hypertensive crisis or hypertensive encephalopathy •Significan
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To evaluate the efficacy of atezolizumab (Atezo)+ bevacizumab (Bev)+ cisplatin and gemcitabine (CisGem) compared with Atezo+ placebo (PBO)+CisGem based on progression free survival;Secondary Objective: •To evaluate the efficacy of Atezo+Bev+CisGem compared with Atezo+PBO+CisGem based on overall survival, confirmed objective response rate, duration of response, disease control rate, time to confirmed deterioration •To evaluate the safety of Atezo+Bev+CisGem compared with Atezo+PBO+CisGem •To characterize the pharmacokinetics of atezolizumab when given in combination with bevacizumab and/or gemcitabine/cisplatin •To evaluate the immune response to atezolizumab ;Primary end point(s): 1. Progression free survival;Timepoint(s) of evaluation of this end point: 1. Up to 5 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall survival 2. Confirmed objective response rate as determined by the investigator according to RECIST v1.1 3. Duration of response as determined by the investigator according to RECIST v1.1 4. Disease control rate as determined by the investigator according to RECIST v1.1 5. Time to confirmed deterioration 6. Incidence and severity of adverse events, with severity determined according to NCI CTCAE v5.0 7. Change from baseline in targeted vital signs 8. Change from baseline in targeted clinical laboratory test results 9. Serum concentration of atezolizumab at specified timepoints 10. Prevalence of ADAs to atezolizumab at baseline and incidence of ADAs to atezolizumab during the study 10. Prevalence of ADAs to atezolizumab at baseline and incidence of ADAs to atezolizumab during the study ;Timepoint(s) of evaluation of this end point: 1-6. Up to 5 years 7-8. Baseline (Day -28 to -1) to 5 years 9-10. Day 1 of Cycle 1, 2, 3, 4, 8, 12, and 16, at treatment discontinuation visit | — |
Countries
Canada, China, France, Hong Kong, Italy, Korea, Republic of, Poland, Russian Federation, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd.
Outcome results
None listed