Clinical trial NCT05771480: Durvalumab With Chemotherapy as First Line Treatment in Patients With Advanced Biliary Tract Cancers (aBTCs)
Official title: A Phase IIIb, Single Arm, Open-label, Multicentre Study of Durvalumab in Combination With Chemotherapy for the First Line Treatment for Patients With Advanced Biliary Tract Cancers (TOURMALINE)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Biliary Tract Cancer
Keywords: monoclonal antibodies
PD-L1 antagonist
Durvalumab
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-03-16
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a single arm study with durvalumab in combination with investigator's choice of 7 different background gemcitabine-based chemotherapy regimens in participants with aBTC.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of participants with Grade 3 or 4 possibly related adverse event (PRAE)
timeFrame: Within 6 months after the initiation of Investigational Medicinal Product (IMP)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From the date of the first dose of IMP until death due to any cause [approx. upto 33 months]
measure: Objective Response Rate (ORR)
timeFrame: 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]
measure: Progression-Free Survival (PFS)
timeFrame: From the date of the first dose of IMP until until the date of objective PD or death [approx. up to 33 months]
measure: Disease Control Rate (DCR)
timeFrame: Week 24 and Week 32
measure: Duration of Response (DOR)
timeFrame: From the date of first documented response until the first date of documented progression or death in the absence of disease progression [approx. up to 33 months]
measure: Duration of Treatment (DOT)
timeFrame: From date of start of IMP, until 27 days after last dose of IMP or date of death [approx. up to 33 months]
measure: Number of participants with AEs, including PRAEs, adverse events of special interest (AESIs), immune-mediated adverse events (imAEs) and serious adverse events (SAEs)
timeFrame: From the date of first dose of IMP until long-term follow-up i.e. until 90 days following discontinuation of the last dose of IMP [approx. up to 33 months]
measure: Number of participants with IRRs and hypersensitivity/anaphylactic reactions
timeFrame: From the date of first dose of IMP until 90 days following discontinuation of the last dose of IMP [approx. up to 33 months]
measure: European Organization for Research and Treatment of Cancer 30-item core quality of life questionnaire (EORTC QLQ C-30)
timeFrame: From date of first dose of IMP, until the date of the first clinically meaningful deterioration [approx. up to 33 months]
measure: EORTC QLQ-BIL21 Score
timeFrame: From date of first dose of IMP, until the date of the first clinically meaningful deterioration [approx. up to 33 months]
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Research Site
state: Alabama
city: Orange
country: United States
facility: Research Site
state: California
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Clichy
country: France
facility: Research Site
city: Dijon
country: France
facility: Research Site
city: Montpellier Cedex 5
country: France
facility: Research Site
city: Villejuif
country: France
facility: Research Site
city: Chemnitz
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Castelfranco Veneto
country: Italy
facility: Research Site
city: Foggia
country: Italy
facility: Research Site
city: Palermo
country: Italy
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Rozzano
country: Italy
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Kanazawa-shi
country: Japan
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Kyoto
country: Japan
facility: Research Site
city: Osaka
country: Japan
facility: Research Site
city: Sendai
country: Japan
facility: Research Site
city: Ube
country: Japan
facility: Research Site
city: Wakayama
country: Japan
facility: Research Site
city: Yokohama
country: Japan
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
Study officials:
References: