Durvalumab With Chemotherapy as First Line Treatment in Patients With Advanced Biliary Tract Cancers (aBTCs)

NCT ID: NCT05771480

Last Updated: 2025-11-21

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 142 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-16
• Study Completion Date: 2026-03-17

Brief Summary

A study to assess the safety and efficacy of durvalumab in combination with gemcitabine-based chemotherapy regimens in participants with aBTC.

Detailed Description

This study involves assessing the safety and efficacy of durvalumab in combination with different gemcitabine-based chemotherapy regimens as first line therapy for aBTC. The target population of interest in this study is participants with aBTC who are ≥ 18 years of age and above legal age per local regulations with WHO/ECOG PS of 0 to 2 at enrolment and who are not eligible for locoregional therapy. Participants with WHO/ECOG PS 2 will be capped at 20% of the overall treated participant population.

The study consists of 4 periods: screening period (Day-28 to Day -1), treatment period up to 8 cycles of gemcitabine-based chemotherapy regimens with durvalumab, maintenance treatment with durvalumab alone or in combination with gemcitabine-based chemotherapy (with the exception of paclitaxel), and then safety and survival follow-up.

Conditions

Biliary Tract Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Durvalumab + Gemcitabine based chemotherapy

Participants will receive durvalumab 1500mg every 3 or 4 weeks, in combination with continuation of all or some of the original background gemcitabine based chemotherapy every 3 or 2 weeks for up to a maximum of 8 cycles of chemotherapy. Durvalumab 1500mg is given as a 60-minute IV infusion in the first cycle (Day 1) and as a 30-minute IV infusion in following cycles.

Upon completing 8 cycles of background gemcitabine-chemotherapy, or after discontinuing any of the combination chemotherapies due to toxicity before completing 8 cycles, participants are eligible to continue receiving durvalumab 1500 mg IV every 4 weeks either alone or in combination with gemcitabine-based chemotherapy (with the exception of paclitaxel), as per investigator's discretion.

Group Type: EXPERIMENTAL

Durvalumab

Intervention Type: BIOLOGICAL

Participants will receive 1500 mg every 3 weeks, or every 4 weeks (in combination with chemotherapy every 3 weeks, or every 2 weeks, respectively) from cycle 1 to cycle 8 of chemotherapy. Upon completion, participants will receive 1500 mg every 4 weeks (as monotherapy)

Gemcitabine monotherapy

Intervention Type: DRUG

Gemcitabine monotherapy as background gemcitabine-based chemotherapy every 3 weeks (i.e., 8 cycles of durvalumab)

Gemcitabine + cisplatin

Intervention Type: DRUG

Gemcitabine plus cisplatin as background gemcitabine-based chemotherapy every 3 weeks (i.e., 8 cycles of durvalumab) for WHO/ECOG PS 2 participants only

Gemcitabine + oxaliplatin

Intervention Type: DRUG

Gemcitabine + oxaliplatin as background gemcitabine-based chemotherapy every 3 weeks (i.e., 8 cycles of durvalumab)

Gemcitabine + carboplatin

Intervention Type: DRUG

Gemcitabine + carboplatin as background gemcitabine-based chemotherapy every 3 weeks (i.e., 8 cycles of durvalumab)

Gemcitabine + cisplatin + S-1

Intervention Type: DRUG

Gemcitabine + cisplatin + S-1 as background gemcitabine-based chemotherapy every 2 weeks (i.e, 4 cycles of durvalumab)

Gemcitabine + S-1

Intervention Type: DRUG

Gemcitabine + S-1 as background gemcitabine-based chemotherapy every 3 weeks (i.e., 8 cycles of durvalumab)

Gemcitabine + cisplatin + albumin-bound paclitaxel

Intervention Type: DRUG

Gemcitabine + cisplatin + albumin-bound paclitaxel as background gemcitabine-based chemotherapy every 3 weeks (i.e., 8 cycles of durvalumab)

Interventions

Durvalumab

Participants will receive 1500 mg every 3 weeks, or every 4 weeks (in combination with chemotherapy every 3 weeks, or every 2 weeks, respectively) from cycle 1 to cycle 8 of chemotherapy. Upon completion, participants will receive 1500 mg every 4 weeks (as monotherapy)

Intervention Type: BIOLOGICAL

Gemcitabine monotherapy

Gemcitabine monotherapy as background gemcitabine-based chemotherapy every 3 weeks (i.e., 8 cycles of durvalumab)

Intervention Type: DRUG

Gemcitabine + cisplatin

Gemcitabine plus cisplatin as background gemcitabine-based chemotherapy every 3 weeks (i.e., 8 cycles of durvalumab) for WHO/ECOG PS 2 participants only

Intervention Type: DRUG

Gemcitabine + oxaliplatin

Gemcitabine + oxaliplatin as background gemcitabine-based chemotherapy every 3 weeks (i.e., 8 cycles of durvalumab)

Intervention Type: DRUG

Gemcitabine + carboplatin

Gemcitabine + carboplatin as background gemcitabine-based chemotherapy every 3 weeks (i.e., 8 cycles of durvalumab)

Intervention Type: DRUG

Gemcitabine + cisplatin + S-1

Gemcitabine + cisplatin + S-1 as background gemcitabine-based chemotherapy every 2 weeks (i.e, 4 cycles of durvalumab)

Intervention Type: DRUG

Gemcitabine + S-1

Gemcitabine + S-1 as background gemcitabine-based chemotherapy every 3 weeks (i.e., 8 cycles of durvalumab)

Intervention Type: DRUG

Gemcitabine + cisplatin + albumin-bound paclitaxel

Gemcitabine + cisplatin + albumin-bound paclitaxel as background gemcitabine-based chemotherapy every 3 weeks (i.e., 8 cycles of durvalumab)

Intervention Type: DRUG

Other Intervention Names

Background Gemcitabine-based Chemotherapy Regimen; Background Gemcitabine-based Chemotherapy Regimen; Background Gemcitabine-based Chemotherapy Regimen; Background Gemcitabine-based Chemotherapy Regimen; Background Gemcitabine-based Chemotherapy Regimen; Background Gemcitabine-based Chemotherapy Regimen.; This regimen is not allowed for countries in the European Union.; Background Gemcitabine-based Chemotherapy Regimen; This regimen is not allowed for countries in the European Union.; Background gemcitabine-based chemotherapy Regimen; This regimen is not allowed for countries in the European Union.

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed, unresectable advanced or metastatic biliary tract carcinoma (BTC) including cholangiocarcinoma (intrahepatic or extrahepatic), gallbladder carcinoma, and ampulla of Vater (AoV) carcinoma
• Participants with unresectable or metastatic BTC
• A World Health Organisation Eastern Cooperative Oncology Group Performance Status (WHO/ECOG PS) of 0 to 2
• At least one lesion that qualifies as a Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) target lesion at baseline
• Adequate organ and bone marrow function
• Body weight of > 30 kg
• Negative pregnancy test (serum) for women of childbearing potential
• Female participants must be one year post-menopausal (amenorrhoeic for 12 months without an alternative medical cause)
• Male and female participants and their partners must be surgically sterile or on their chosen method of birth control as per the protocol.

Exclusion Criteria

• Any evidence of diseases such as severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diseases, active infection, active interstitial lung disease/pneumonitis, serious chronic gastrointestinal conditions associated with diarrhoea, psychiatric illness/social situations, history of uncontrolled or symptomatic cardiac disease, and history of allogenic organ transplant
• Active or prior documented autoimmune or inflammatory disorders
• History of another primary malignancy, except for malignancy treated with curative intent and with no known active disease ≥ 5 years before the first dose of study intervention
• History of leptomeningeal carcinomatosis
• History of active primary immunodeficiency
• Known to have tested positive for human immunodeficiency virus [HIV] (positive HIV 1/2 antibodies) or active tuberculosis infection
• Participants co-infected with Hepatitis B virus (HBV) and Hepatitis C virus (HCV) or co-infected with HBV and Hepatitis D virus (HDV)
• Persistent toxicities (Common Terminology Criteria for Adverse Events [CTCAE] Grade > 1) caused by previous anticancer therapy
• Central nervous system metastases requiring treatment or history of spinal cord compression
• Known allergy or hypersensitivity to any of the study intervention or any of the study intervention excipients.
• Any concurrent chemotherapy, other than the one allowed in the study, investigational medicinal product (IMP), biologic, or hormonal therapy for cancer treatment
• Palliative radiotherapy with a limited field of radiation within 2 weeks of the first dose of study intervention, or radiotherapy with a wide field of radiation or radiotherapy affecting more than 30% of the bone marrow within 4 weeks before the first dose of study intervention
• Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention
• Major surgical procedure within 28 days prior to the first dose of IMP
• Prior exposure to immune-mediated therapy excluding therapeutic anticancer vaccines
• Receipt of the last dose of anticancer therapy within 28 days prior to the first dose of IMP

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 130 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Mobile, Alabama, United States

Research Site

Orange, California, United States

Research Site

Washington D.C., District of Columbia, United States

Research Site

Portland, Oregon, United States

Research Site

Clichy, , France

Research Site

Dijon, , France

Research Site

Montpellier, , France

Research Site

Villejuif, , France

Research Site

Chemnitz, , Germany

Research Site

Hanover, , Germany

Research Site

Castelfranco Veneto, , Italy

Research Site

Foggia, , Italy

Research Site

Palermo, , Italy

Research Site

Pisa, , Italy

Research Site

Rozzano, , Italy

Research Site

Chūōku, , Japan

Research Site

Kanazawa, , Japan

Research Site

Kashiwa, , Japan

Research Site

Kyoto, , Japan

Research Site

Osaka, , Japan

Research Site

Sendai, , Japan

Research Site

Ube, , Japan

Research Site

Wakayama, , Japan

Research Site

Yokohama, , Japan

Research Site

Singapore, , Singapore

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Research Site

Barcelona, , Spain

Research Site

Madrid, , Spain

Research Site

Madrid, , Spain

Research Site

Madrid, , Spain

Research Site

Pamplona, , Spain

Research Site

Seville, , Spain

Countries

United States; France; Germany; Italy; Japan; Singapore; South Korea; Spain

Other Identifiers

2022-502043-35

Identifier Type: REGISTRY

Identifier Source: secondary_id

2022-002527-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D4191C00140

Identifier Type: -

Identifier Source: org_study_id