A Phase IIIb, Single Arm, Open-label, Multi-center Study on Durvalumab in Combination With Gemcitabine-based Chemotherapy as First Line Treatment for Chinese Patients With Unresectable Biliary Tract Cancers

AstraZeneca1 site in 1 country116 target enrollmentJuly 21, 2023

ConditionsBiliary Tract Cancers

Interventionsdurvalumab

Drugsdurvalumab

Overview

Phase: Phase 3
Intervention: durvalumab
Conditions: Biliary Tract Cancers
Sponsor: AstraZeneca
Enrollment: 116
Locations: 1
Primary Endpoint: The incidence of Possible related adverse events(PRAE) Grade 3 or 4
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a Phase IIIb, open-label, single arm, multicentre study to assess the safety and efficacy of durvalumab in combination with investigator's choice of 3 different gemcitabine-based chemotherapy regimens in participants with aBTC with a WHO/ECOG PS of 0 to 2 at enrolment.

Detailed Description

The primary objective of the study is to assess the safety of durvalumab combined with gemcitabine-based chemotherapy for participants with advanced BTC who have not previously received systemic therapy for advanced or metastatic BTC with WHO/ECOG PS of 0 to 2. Eligible participants will received durvalumab in combination with gemcitabine-based chemotherapy(Gemcitabine+Oxalipatin; Gemcitabine+S1, Gemcitabine+Cisplatin) by investigator's choice.

Registry

clinicaltrials.gov

Start Date

July 21, 2023

End Date

February 7, 2025

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

AstraZeneca

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Participant must be ≥ 18 years at the time of screening.
•Histologically confirmed, unresectable advanced or metastatic BTC including cholangiocarcinoma (intrahepatic or extrahepatic), gallbladder carcinoma.
•Participants with previously untreated disease are eligible if presented with unresectable or metastatic BTC at initial diagnosis.
•Prior curative intent treatment (surgery and, if given in the adjuvant setting, chemotherapy and/or radiation) is permitted, with recurrent disease \>6 months. This includes participants with residual disease after surgery, who received chemotherapy, chemoembolization, or radiotherapy.
•A WHO/ECOG PS of 0 to
•At least one lesion that qualifies as a RECIST 1.1 TL at baseline.
•Participants with HBV infection (as characterised by positive HBsAg and/or anti-HBcAb with detectable HBV DNA, as per local laboratory standards) must be treated with antiviral therapy, as per institutional practice, to ensure adequate viral suppression (as per local laboratory standards) prior to enrolment. Participants must remain on antiviral therapy for the study duration and for 6 months after the last dose of study intervention. Participants who test positive for anti-HBc with undetectable HBV DNA (as per local laboratory standards) do not require antiviral therapy prior to enrolment. These participants will be tested at every cycle to monitor HBV DNA levels and initiate antiviral therapy if HBV DNA is detected (as per local laboratory standards). HBV DNA detectable participants must initiate and remain on antiviral therapy for the study duration and for 6 months after the last dose of study intervention.
•Adequate organ and marrow function, as defined below.
•Haemoglobin ≥ 9 g/dL
•Absolute neutrophil count ≥ 1.5 × 109/L

Exclusion Criteria

•Ampullary carcinoma.
•As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diseases, active infection, active ILD/pneumonitis, serious chronic gastrointestinal conditions associated with diarrhoea, psychiatric illness/social situations), history of allogenic organ transplant, which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol.
•Active or prior documented autoimmune or inflammatory disorders including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis\], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc). The following are exceptions to this criterion:
•Participants with vitiligo or alopecia.
•Participants with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement.
•Any chronic skin condition that does not require systemic therapy.
•Participants without an active disease in the last 5 years may be included but only after consultation with the study physician.
•Participants with celiac disease controlled by diet alone.
•Participants with ≥ Grade 2 lymphopenia will be evaluated on a case-by- case basis after consultation with the study physician
•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 and of low potential risk for recurrence, basal cell carcinoma of the skin, squamous cell carcinoma of the skin or lentigo maligna that has undergone potentially curative therapy, or adequately treated carcinoma in situ without evidence of disease.

Arms & Interventions

durvalumab in combination with gemcitabine-based chemotherapy

single-arm

Intervention: durvalumab

Outcomes

Primary Outcomes

The incidence of Possible related adverse events(PRAE) Grade 3 or 4

Time Frame: Within 6 months after the initiation of study intervention.

The primary endpoint of this study is the incidence of Grade 3/4 PRAEs (CTCAE v5.0) of durvalumab combined with gemcitabine-based chemotherapy within 6 months of starting study intervention regardless of length of infusion. PRAEs are where the investigator answered yes to the question "Do you consider that there is a reasonable possibility that the event may have been caused by the investigational product?".

Secondary Outcomes

Overall Survival(OS)(From first dose of study intervention until death, up to 67.9% OS maturity or at least 12 months after the last subject enrolled, which occurs first)
Objective Response Rate (ORR)(From first dose of study intervention until disease progression or death (whichever occurs first), up to approximately 3 months after the last subject enrolled)
Progression-free Survival (PFS)(From first dose of study intervention until disease progression or death (whichever occurs first), up to approximately 6 months after the last subject enrolled)
Disease Control Rate(DCR)(From first dose of study intervention until disease progression or death (whichever occurs first), up to approximately 6 months after the last subject enrolled)
Duration of Response(DOR)(From first dose of study intervention until disease progression or death (whichever occurs first), up to approximately 6 months after the last subject enrolled)
Duration of Treatment(DOT)(From first dose of study intervention until last dose or death (whichever occurs first), up to 67.9% OS maturity or at least 12 months after the last subject enrolled, which occurs first)
Patient-reported Outcomes(PROs)(From first dose of study intervention until 90 days after last dose or death (whichever occurs first))
Incidence of treatment-emergent adverse events(AEs)(From first dose of study intervention until 90 days after last dose or death (whichever occurs first))
Severity of treatment-emergent adverse events(AEs)(From first dose of study intervention until 90 days after last dose or death (whichever occurs first))
Intervention/treatment of treatment-emergent adverse events(AEs)(From first dose of study intervention until 90 days after last dose or death (whichever occurs first))
Outcome of treatment-emergent adverse events(AEs)(From first dose of study intervention until 90 days after last dose or death (whichever occurs first))
Causality of treatment-emergent adverse events(AEs)(From first dose of study intervention until 90 days after last dose or death (whichever occurs first))
Adverse Events(AEs) resulting in study intervention interruption and discontinuation(From first dose of study intervention until 90 days after last dose or death (whichever occurs first))