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
Interventions
Trade Name: GEMCITABINA TEVA
Product Name: Gemcitabine
Product Code: [-]
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: GEMCITABINA
Current Sponsor code: -
Concentration un
Sponsors
F. HOFFMANN - 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/mcL, 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 D1 C1 •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 CTscan •Sign. cardiovascular disease within 3 months prior to D1 C1, unstable arrhythmia, or unstable angina •History of malignancy other than BTC within 5 years prior to screening •Active tuberculosis •Severe infection within 4 weeks prior to D1 C1 •Treatment with oral or IV antibiotics within 2 weeks prior to D1 C1 •Prior allogeneic stem cell or solid organ transplantation •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 •Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of atezo or within 6 months after the final dose of beva, 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 atezo or beva formulations •Treatment with a live, attenuated vaccine within 4 weeks prior to D1 C1 or anticipation of need for such a vaccine during atezo treatment or within 5 months after the final dose of atezo •Treatment with investigational therapy within 4 weeks prior to D1 C1 •Prior treatment with CD137 agonists or immune checkpoint blockade therapies •Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives prior to D1 C1 •Treatment with systemic immunosuppressive medication within 2 weeks prior to D1 C1 or anticipation of need for systemic immunosuppressive medication during study treatment •Inadequately controlled arterial hypertension (defined as systolic 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 •Significant vascular disease within 6 months prior to D1 C1 •History of hemoptysis within 1 month prior to D1 C1 •Evidence of bleeding diathesis or significant coagulopathy •Current or recent use of aspirin ( > 325 mg/day)or current or recent treatment with dipyramidole, ticlopidine, clopidogrel, and cilostazol •Current or recent use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purpose •Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 3 days prior to D1 C1 •History of abdominal or tracheoesophageal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to D1 C1 •Evidence of abdominal free air that is not explained by paracentesi
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;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