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

Biliary Tract Cancer Clinical Trial

— TOURMALINE  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05771480
• Other study ID #: D4191C00140
• Secondary ID: 2022-502043-3520
• Status: Recruiting
• Phase: Phase 3
• Start date: August 16, 2023
• Est. completion date: March 17, 2026

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: March 17, 2026
• Est. primary completion date: September 17, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

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

Related Conditions & MeSH terms

• Biliary Tract Cancer
• Biliary Tract Neoplasms

Intervention

Biological:
• 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)

Drug:
• Gemcitabine monotherapy
Gemcitabine monotherapy as background gemcitabine-based chemotherapy every 3 weeks (i.e., 8 cycles of durvalumab)
• 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
• Gemcitabine + oxaliplatin
Gemcitabine + oxaliplatin as background gemcitabine-based chemotherapy every 3 weeks (i.e., 8 cycles of durvalumab)
• Gemcitabine + carboplatin
Gemcitabine + carboplatin as background gemcitabine-based chemotherapy every 3 weeks (i.e., 8 cycles of durvalumab)
• Gemcitabine + cisplatin + S-1
Gemcitabine + cisplatin + S-1 as background gemcitabine-based chemotherapy every 2 weeks (i.e, 4 cycles of durvalumab)
• Gemcitabine + S-1
Gemcitabine + S-1 as background gemcitabine-based chemotherapy every 3 weeks (i.e., 8 cycles of durvalumab)
• Gemcitabine + cisplatin + albumin-bound paclitaxel
Gemcitabine + cisplatin + albumin-bound paclitaxel as background gemcitabine-based chemotherapy every 3 weeks (i.e., 8 cycles of durvalumab)

Locations

Country	Name	City	State
France	Research Site	Clichy
France	Research Site	Dijon
France	Research Site	Lyon Cedex 03
France	Research Site	Montpellier Cedex 5
France	Research Site	Pessac
France	Research Site	Rennes
France	Research Site	Villejuif
Germany	Research Site	Chemnitz
Germany	Research Site	Freudenstadt
Germany	Research Site	Hannover
Germany	Research Site	Muenchen
Italy	Research Site	Castelfranco Veneto
Italy	Research Site	Foggia
Italy	Research Site	Palermo
Italy	Research Site	Pisa
Italy	Research Site	Rozzano
Japan	Research Site	Chuo-ku
Japan	Research Site	Kanazawa-shi
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
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Singapore	Research Site	Singapore
Singapore	Research Site	Singapore
Singapore	Research Site	Singapore
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Pamplona
Spain	Research Site	Sevilla
United States	Research Site	Mobile	Alabama
United States	Research Site	New York	New York
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Orange	California
United States	Research Site	Portland	Oregon
United States	Research Site	Washington	District of Columbia
United States	Research Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Singapore,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Within 6 months after the initiation of Investigational Medicinal Product (IMP)
Secondary	Overall Survival (OS)	OS is defined as the time from the date of the first dose of IMP until death due to any cause.	From the date of the first dose of IMP until death due to any cause [approx. upto 33 months]
Secondary	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.	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]
Secondary	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.	From the date of the first dose of IMP until until the date of objective PD or death [approx. up to 33 months]
Secondary	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.	Week 24 and Week 32
Secondary	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.	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]
Secondary	Duration of Treatment (DOT)	DOT is defined as time on study intervention.	From date of start of IMP, until 27 days after last dose of IMP or date of death [approx. up to 33 months]
Secondary	Number of participants with AEs, including PRAEs, adverse events of special interest (AESIs), immune-mediated adverse events (imAEs) and serious adverse events (SAEs)	To assess the safety and tolerability profile of durvalumab combined with background gemcitabine-based chemotherapy	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]
Secondary	Number of participants with IRRs and hypersensitivity/anaphylactic reactions	To assess the safety and tolerability profile of durvalumab combined with background gemcitabine-based chemotherapy	From the date of first dose of IMP until 90 days following discontinuation of the last dose of IMP [approx. up to 33 months]
Secondary	European Organization for Research and Treatment of Cancer 30-item core quality of life questionnaire (EORTC QLQ C-30)	To assess disease and treatment related symptoms and HRQoL. EORTC QLQ-C30 consists of 30 items and measures symptoms, functioning, and global health status/QoL for all cancer types. Questions are grouped into 5 multi-item functional scales (physical, role, emotional, cognitive, and social), 3 multi-item symptom scales (fatigue, pain, and nausea/vomiting), a 2-item global QoL scale, 5 single items assessing additional symptoms commonly reported by cancer participants (dyspnoea, loss of appetite, insomnia, constipation, and diarrhoea), and one item on the financial impact of the disease. The EORTC QLQ-C30 is a valid and reliable PRO instrument in this participant population	From date of first dose of IMP, until the date of the first clinically meaningful deterioration [approx. up to 33 months]
Secondary	EORTC QLQ-BIL21 Score	To assess disease- and treatment related symptoms and HRQoL. The EORTC QLQ-BIL21 is a disease-specific (cholangiocarcinoma and cancer of the gallbladder) questionnaire. It consists of 21 items including one question each for side effects, equipment issues, and weight loss, as well as 5 scales (eating symptoms, jaundice symptoms, tiredness, pain, and anxiety). A higher score indicates greater difficulties. The EORTC QLQ-BIL21 is a valid and reliable PRO instrument in this participant population.	From date of first dose of IMP, until the date of the first clinically meaningful deterioration [approx. up to 33 months]