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

• Sponsor: AstraZeneca (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05771480
• Collaborator: (none)
• Enrollment: 160
• Locations: 37
• Arm: 1
• Anticipated Duration (Months): 32
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Biliary Tract Cancer	Biological: Durvalumab; Drug: Gemcitabine monotherapy; Drug: Gemcitabine + cisplatin; Drug: Gemcitabine + oxaliplatin; Drug: Gemcitabine + carboplatin; Drug: Gemcitabine + cisplatin + S-1; Drug: Gemcitabine + S-1; Drug: Gemcitabine + cisplatin + albumin-bound paclitaxel	Phase 3

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 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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 160 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• 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.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.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Anticipated Study Start Date: Jul 30, 2023
• Anticipated Primary Completion Date: Mar 31, 2026
• Anticipated Study Completion Date: Mar 31, 2026

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Durvalumab + Gemcitabine based chemotherapy Participants will receive durvalumab 1500 mg as a 60-minute IV infusion in the first cycle (Day 1) and as a 30 -minute IV infusion in the following cycles, in combination with background gemcitabine-based chemotherapy every three or two weeks for up to a maximum of 8 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.

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

Outcome Measures

Primary Outcome Measures

1. Number of participants with Grade 3 or 4 possibly related adverse event (PRAE) [From the date of first dose of IMP until 90 days following discontinuation of the last dose of IMP [approx. up to 33 months]]

   PRAE is defined as an AE which has been assessed by the investigator to be possibly related to IMP.

Secondary Outcome Measures

1. Overall Survival (OS) [From the date of the first dose of IMP until death due to any cause [approx. upto 33 months]]

   OS is defined as the time from the date of the first dose of IMP until death due to any cause.

2. Objective Response Rate (ORR) [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]]

   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.

3. Progression-Free Survival (PFS) [From the date of the first dose of IMP until until the date of objective PD or death [approx. up to 33 months]]

   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.

4. Disease Control Rate (DCR) [Week 24 and Week 32]

   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.

5. Duration of Response (DOR) [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]]

   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.

6. Duration of Treatment (DOT) [From date of start of IMP, until 27 days after last dose of IMP or date of death [approx. up to 33 months]]

   DOT is defined as time on study intervention.

7. Number of participants with AEs, including PRAEs, adverse events of special interest (AESIs), immune-mediated adverse events (imAEs) and serious adverse events (SAEs) [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]]

   To assess the safety and tolerability profile of durvalumab combined with background gemcitabine-based chemotherapy

8. Number of participants with IRRs and hypersensitivity/anaphylactic reactions [From the date of first dose of IMP until 90 days following discontinuation of the last dose of IMP [approx. up to 33 months]]

   To assess the safety and tolerability profile of durvalumab combined with background gemcitabine-based chemotherapy

9. European Organization for Research and Treatment of Cancer 30-item core quality of life questionnaire (EORTC QLQ C-30) [From date of first dose of IMP, until the date of the first clinically meaningful deterioration [approx. up to 33 months]]

   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

10. EORTC QLQ-BIL21 Score [From date of first dose of IMP, until the date of the first clinically meaningful deterioration [approx. up to 33 months]]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 130 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 use an acceptable method of contraception 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 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

• History of, or current, brain metastases or 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Orange	California	United States	92868
2	Research Site	Washington	District of Columbia	United States	20007
3	Research Site	Portland	Oregon	United States	97213
4	Research Site	Clichy		France	92110
5	Research Site	Dijon		France	21079
6	Research Site	Lyon Cedex 03		France	69437
7	Research Site	Montpellier Cedex 5		France	34090
8	Research Site	Pessac		France	33604
9	Research Site	Rennes		France	35042
10	Research Site	Villejuif		France	94800
11	Research Site	Chemnitz		Germany	09131
12	Research Site	Hannover		Germany	30625
13	Research Site	Muenchen		Germany	81377
14	Research Site	Pisa		Italy	56126
15	Research Site	Rozzano		Italy	20089
16	Research Site	Chuo-ku		Japan	104-0045
17	Research Site	Kanazawa-shi		Japan	920-8641
18	Research Site	Kashiwa		Japan	227-8577
19	Research Site	Kyoto		Japan	606-8507
20	Research Site	Osaka		Japan	541-8567
21	Research Site	Sendai		Japan	980-8574
22	Research Site	Ube		Japan	755-8505
23	Research Site	Wakayama		Japan	641-8509
24	Research Site	Yokohama		Japan	241-8515
25	Research Site	Seoul		Korea, Republic of	03080
26	Research Site	Seoul		Korea, Republic of	05505
27	Research Site	Seoul		Korea, Republic of	06351
28	Research Site	Singapore		Singapore	169610
29	Research Site	Singapore		Singapore	258499
30	Research Site	Singapore		Singapore	329563
31	Research Site	Barcelona		Spain	08035
32	Research Site	Barcelona		Spain	08036
33	Research Site	Madrid		Spain	28007
34	Research Site	Madrid		Spain	28040
35	Research Site	Madrid		Spain	28041
36	Research Site	Pamplona		Spain	31008
37	Research Site	Sevilla		Spain	41013

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT05771480
• Other Study ID Numbers: D4191C00140
• First Posted: Mar 16, 2023
• Last Update Posted: Mar 16, 2023
• Last Verified: Mar 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by AstraZeneca: monoclonal antibodies; PD-L1 antagonist; Durvalumab
• Additional relevant MeSH terms: Biliary Tract Neoplasms; Gemcitabine; Paclitaxel; Cisplatin; Carboplatin; Oxaliplatin; Durvalumab; Albumin-Bound Paclitaxel

Study Results

No Results Posted as of Mar 16, 2023