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

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ClinicalTrials.gov Identifier: NCT04677504
Recruitment Status : Recruiting
First Posted : December 21, 2020
Last Update Posted : July 27, 2021
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief 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.

Condition or disease Intervention/treatment Phase
Biliary Tract Cancer Drug: Atezolizumab Drug: Bevacizumab Other: Placebo Drug: Cisplatin Drug: Gemcitabine Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : February 23, 2021
Estimated Primary Completion Date : February 21, 2023
Estimated Study Completion Date : April 24, 2023


Arm Intervention/treatment
Experimental: Arm A: Atezo+Bev+CisGem, followed by Atezo+Bev
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.
Drug: Atezolizumab
Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.
Other Name: Tecentriq

Drug: Bevacizumab
Bevacizumab will be administered at a dose of 15 mg/kg intravenously on Day 1 of each 21-day cycle after atezolizumab.
Other Name: Avastin

Drug: Cisplatin
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.

Drug: Gemcitabine
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.

Active Comparator: Arm B: Atezo+PBO+CisGem, followed by Atezo+PBO
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.
Drug: Atezolizumab
Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.
Other Name: Tecentriq

Other: Placebo
Placebo matching bevacizumab will be administered intravenously on Day 1 of each 21-day cycle after atezolizumab.

Drug: Cisplatin
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.

Drug: Gemcitabine
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.




Primary Outcome Measures :
  1. 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) ]
    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 :
  1. Overall Survival (OS) [ Time Frame: Randomization to death from any cause (up to approximately 3-5 years) ]
    OS, defined as the time from randomization to death from any cause.

  2. Confirmed Objective Response Rate (ORR) [ Time Frame: Randomization up to approximately 3-5 years ]
    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.

  3. 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) ]
    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).

  4. Disease Control Rate (DCR) [ Time Frame: Randomization up to approximately 3-5 years ]
    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

  5. Time to Confirmed Deterioration (TTCD) [ Time Frame: Randomization to the first clinically meaningful deterioration (up to approximately 3-5 years) ]
    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.

  6. Percentage of Participants With Adverse Events [ Time Frame: Randomization up to approximately 3-5 years ]
  7. Serum Concentration of atezolizumab [ Time Frame: At pre-defined intervals from administration of study drug up to approximately 3-5 years ]
    Serum concentration of atezolizumab at specified timepoints.

  8. Prevalence of ADAs to Atezolizumab [ Time Frame: Baseline ]
  9. Incidence of ADAs to Atezolizumab [ Time Frame: At pre-defined intervals from administration of study drug up to approximately 3-5 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04677504


Contacts
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Contact: Reference Study ID Number: GO42661 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04677504    
Other Study ID Numbers: GO42661
First Posted: December 21, 2020    Key Record Dates
Last Update Posted: July 27, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here ( https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Biliary Tract Diseases
Digestive System Diseases
Gemcitabine
Bevacizumab
Atezolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors