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

Phase 3Active Not RecruitingNCT05771480

AstraZeneca142 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

142

Conditions

Biliary Tract Cancer

Interventions

DurvalumabBIOLOGICAL

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 monotherapyDRUG

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

Gemcitabine + cisplatinDRUG

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 130 Years

Medical Language ↔ Plain English

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

Locations (34)

Research Site

Outcomes

Primary Outcomes

Number of participants with Grade 3 or 4 possibly related adverse event (PRAE)

PRAE is defined as an AE which has been assessed by the investigator to be possibly related to IMP.

Time frame: Within 6 months after the initiation of Investigational Medicinal Product (IMP)

Secondary Outcomes

Overall Survival (OS)

OS is defined as the time from the date of the first dose of IMP until death due to any cause.

Time frame: From the date of the first dose of IMP until death due to any cause [approx. upto 33 months]

Objective Response Rate (ORR)

ORR is defined as the proportion of participants who have a confirmed CR or confirmed PR, as determined by the investigator at local site per RECIST 1.1.

Time frame: From the date of first dose of IMP until progression, or the last evaluable assessment in the absence of progression [assessed up to 33 months]

Progression-Free Survival (PFS)

PFS is defined as the time from the first dose of IMP until the date of disease progression (PD) or death due to any cause.

Time frame: From the date of the first dose of IMP until until the date of objective PD or death [approx. up to 33 months]

Disease Control Rate (DCR)

DCR is defined as the % of participants who have a best objective response of complete response or partial response (by week 24 or 32), or who have stable disease for 24 or 32 weeks.

Time frame: Week 24 and Week 32

Duration of Response (DOR)

DOR is defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression.

Data from ClinicalTrials.gov

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