Clinical Trials /

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

NCT04677504

Description:

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.

Related Conditions:
  • Biliary Tract Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

  • ORG STUDY ID: GO42661
  • NCT ID: NCT04677504

Conditions

  • Biliary Tract Cancer

Interventions

DrugSynonymsArms
AtezolizumabTecentriqArm A: Atezo+Bev+CisGem, followed by Atezo+Bev
BevacizumabAvastinArm A: Atezo+Bev+CisGem, followed by Atezo+Bev
CisplatinArm A: Atezo+Bev+CisGem, followed by Atezo+Bev
GemcitabineArm A: Atezo+Bev+CisGem, followed by Atezo+Bev

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Arm A: Atezo+Bev+CisGem, followed by Atezo+BevExperimentalParticipants 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.
  • Atezolizumab
  • Bevacizumab
  • Cisplatin
  • Gemcitabine
Arm B: Atezo+PBO+CisGem, followed by Atezo+PBOActive ComparatorParticipants 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.
  • Atezolizumab
  • Cisplatin
  • Gemcitabine

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

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame: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 approximatly 3-5 years)
Safety Issue:
Description:PFS, 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)

Secondary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:Randomization to death from any cause (up to approximately 3-5 years)
Safety Issue:
Description:OS, defined as the time from randomization to death from any cause.
Measure:Confirmed Objective Response Rate (ORR)
Time Frame:Randomization up to approximately 3-5 years
Safety Issue:
Description:Confirmed ORR, defined as the proportion of participants with CR or PR on two consecutive occasions >=4 weeks apart, as determined by the investigator according to RECIST v1.1.
Measure:Duration of Response (DOR)
Time Frame: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 3-5 years)
Safety Issue:
Description:DOR, 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).
Measure:Disease Control Rate (DCR)
Time Frame:Randomization up to approximately 3-5 years
Safety Issue:
Description:DCR, defined as the proportion of patients 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
Measure:Time to Confirmed Deterioration (TTCD)
Time Frame:Randomization to the first clinically meaningful deterioration (up to approximately 3-5 years)
Safety Issue:
Description: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.
Measure:Percentage of Participants With Adverse Events
Time Frame:Randomization up to approximately 3-5 years
Safety Issue:
Description:
Measure:Serum Concentration of atezolizumab
Time Frame:At pre-defined intervals from administration of study drug up to approximately 3-5 years
Safety Issue:
Description:Serum concentration of atezolizumab at specified timepoints.
Measure:Prevalence of ADAs to Atezolizumab
Time Frame:Baseline
Safety Issue:
Description:
Measure:Incidence of ADAs to Atezolizumab
Time Frame:At pre-defined intervals from administration of study drug up to approximately 3-5 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

December 21, 2020