A Phase 3b, Open-label, Multi-center Study on Durvalumab in Combination With Gemcitabine-based Chemotherapy as 1L Treatment for the Chinese Patients With Unresectable Biliary Tract Cancers (BTC)

NCT05924880 | Completed Phase 3

• 1 other identifier: D933AL00006
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 19

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.

Conditions

Biliary Tract Cancers

Outcome Measures

Primary Outcomes (1)

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

  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?".

  Within 6 months after the initiation of study intervention.

Secondary Outcomes (13)

• 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

Study Arms (1)

durvalumab in combination with gemcitabine-based chemotherapy

EXPERIMENTAL

single-arm

Drug: durvalumab

Interventions

durvalumab DRUG

Durvalumab 1500 mg as a 60-minute IV infusion in combination with gemcitabine-based chemotherapy Q3W. Upon completing chemotherapy, or discontinuing chemotherapy due to toxicity, durvalumab 1500 mg IV Q4W alone or in combination with gemcitabine.

Also known as: IMFINZI

durvalumab in combination with gemcitabine-based chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 2.
• 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
• Platelet count ≥ 100 × 109/L
• Serum bilirubin ≤ 2.0 × ULN; this will not apply to participants with confirmed Gilbert's syndrome. Any clinically significant biliary obstruction should be resolved before enrolment.
• ALT and AST ≤ 2.5 × ULN. For participants with hepatic metastases, ALT and AST ≤ 5 × ULN.
• Calculated creatinine clearance \> 50 mL/minute as determined by Cockcroft-Gault (using actual body weight) or 24-hour urine creatinine clearance. For chemotherapy regimens including carboplatin, oxaliplatin, or gemcitabine as monotherapy, the recommended threshold for calculated creatinine clearance is \> 40 mL/minute as determined by Cockcroft-Gault (using actual body weight) or 24-hour urine creatinine clearance.
• Must have a life expectancy of at least 12 weeks.

You may not qualify if:

• 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.
• History of leptomeningeal carcinomatosis.
• History of active primary immunodeficiency.
• Known to have tested positive for HIV (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).
• Participants co-infected with HBV (presence of HBsAg and/or anti-HBcAb with detectable HBV DNA, as per local laboratory standards) and HCV (presence of anti-HCV antibodies), or coinfected with HBV and HDV (presence of anti-HDV antibodies).
• Persistent toxicities (CTCAE Grade \> 2) caused by previous anticancer therapy; alopecia and vitiligo are excluded toxicities.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (19)

Research Site

Beijing, 100142, China

Location

Research Site

Beijing, 100210, China

Location

Research Site

Changsha, 410013, China

Location

Research Site

Chongqing, 400038, China

Location

Research Site

Fuzhou, 350011, China

Location

Research Site

Guangzhou, 510280, China

Location

Research Site

Harbin, 150049, China

Location

Research Site

Hefei, 230001, China

Location

Research Site

Hefei, 230022, China

Location

Research Site

Jinan, 250117, China

Location

Research Site

Nanchang, 330000, China

Location

Research Site

Shanghai, 200032, China

Location

Research Site

Shenyang, 110001, China

Location

Research Site

Tianjin, 300050, China

Location

Research Site

Tianjin, 300060, China

Location

Research Site

Wuhan, 430030, China

Location

Research Site

Wuhan, 430071, China

Location

Research Site

Xi'an, 710061, China

Location

Research Site

Xiamen, 361015, China

Location

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2023
• First Posted: June 29, 2023
• Study Start: July 21, 2023
• Primary Completion: February 7, 2025
• Study Completion: February 7, 2025
• Last Updated: April 22, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

CN (19)