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

AstraZeneca

Status and phase

Active, not recruiting

Phase 3

Conditions

Biliary Tract Cancer

Treatments

Drug: Gemcitabine + S-1

Drug: Gemcitabine + cisplatin

Drug: Gemcitabine + carboplatin

Drug: Gemcitabine + cisplatin + S-1

Drug: Gemcitabine + oxaliplatin

Biological: Durvalumab

Drug: Gemcitabine monotherapy

Drug: Gemcitabine + cisplatin + albumin-bound paclitaxel

Study type

Interventional

Funder types

Industry

Identifiers

NCT05771480

D4191C00140

2022-502043-35 (Registry Identifier)

2022-002527-35 (EudraCT Number)

Details and patient eligibility

About

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

Full 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.

Enrollment

142 patients

Sex

All

Ages

18 to 130 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

142 participants in 1 patient group

Durvalumab + Gemcitabine based chemotherapy

Experimental group

Description:

Participants will receive durvalumab 1500mg every 3 or 4 weeks, in combination with continuation of all or some of the original background gemcitabine based chemotherapy every 3 or 2 weeks for up to a maximum of 8 cycles of chemotherapy. Durvalumab 1500mg is given as a 60-minute IV infusion in the first cycle (Day 1) and as a 30-minute IV infusion in following cycles. Upon completing 8 cycles of background gemcitabine-chemotherapy, or after discontinuing any of the combination chemotherapies due to toxicity before completing 8 cycles, participants are eligible to continue receiving durvalumab 1500 mg IV every 4 weeks either alone or in combination with gemcitabine-based chemotherapy (with the exception of paclitaxel), as per investigator's discretion.

Treatment: