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)

Phase 1

Recruiting

• Conditions: Advanced Biliary Tract Cancers; MedDRA version: 20.0Level: LLTClassification code: 10004676Term: Biliary tract disease Class: 10019805; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: CTIS2022-502043-35-01
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-11-22
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 216

Inclusion Criteria

1. Participant must be = 18 years and above legal age per local regulations at the time of screening., 10. Body weight of > 30 kg., 11. Male or female., 12. Negative pregnancy test (serum) for women of childbearing potential., 13. Female participants must be one year post-menopausal (amenorrhoeic for 12 months without an alternative medical cause), surgically sterile, or using one highly effective form of birth control (a highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly). Women of childbearing potential must agree to use one highly effective method of birth control (see Appendix H in the protocol for a complete list of highly effective birth control methods) from the time of screening throughout the total duration of the study and up to 90 days after the last dose of durvalumab or up to end of the period specified in the SmPC or package insert of the background gemcitabine-based chemotherapy agents, whichever is longer. - Non-sterilised male partners of a woman of childbearing potential must use a male condom plus spermicide (condom alone in countries where spermicides are not approved) throughout this period. Cessation of birth control after this point should be discussed with a responsible physician. Periodic abstinence, as well as the rhythm and withdrawal methods are not acceptable methods of birth control., 14. Male participants who intend to be sexually active with a female partner of childbearing potential must be surgically sterile or on their chosen method of birth control from the time of screening throughout the total duration of the study and up to 90 days after the last dose of durvalumab or up to end of the period specified in the SmPC or package insert of the background gemcitabine-based chemotherapy agents, whichever is longer, to prevent pregnancy in a partner. Male participants must not donate or bank sperm during this same time period. - Female partners (of childbearing potential) of male participants must also use a highly effective method of contraception throughout this period., 15. Participant is capable of giving signed informed consent as described in Appendix A, Section A3 in the protocol which includes compliance with the requirements and restrictions listed in the ICF and in this protocol., 16. Written informed consent from the participant has been obtained prior to any study-related procedures., 17. Provision of signed and dated written Optional Genomics Initiative Research Information and Consent Form prior to collection of sample for optional genomics initiative research that supports Genomic Initiative., 2. Histologically confirmed, unresectable advanced or metastatic BTC including cholangiocarcinoma (intrahepatic or extrahepatic), gallbladder carcinoma, and AoV carcinoma, 3. Participants with previously untreated disease are eligible if presented with unresectable or metastatic BTC at initial diagnosis., 4. Prior curative intent treatment (surgery and, if given in the adjuvant setting, chemotherapy and/or radiation) is permitted, regardless of time to recurrence. This includes participants with residual disease after surgery, who received chemotherapy, chemoembolization, or radiotherapy., 5. A WHO/ECOG PS of 0 to 2., 6. At least one lesion that qualifies as a RECIST 1.1 TL at baseline., 7. Participants with HBV infection (as characterised by positive HBsAg and/or anti-HBcAb with detectable HBV DNA, as

Exclusion Criteria

1. 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 uncontrolled or symptomatic cardiac disease, and 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., 10. Known allergy or hypersensitivity to any of the study intervention or any of the study intervention excipients., 11. Any concurrent chemotherapy, other than the one allowed in the study, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for noncancer- related conditions (eg, hormone replacement therapy) is acceptable., 12. 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. Prior locoregional therapy, such as radioembolization, is allowed as long as done more than 2 weeks prior., 13. Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention (see Appendix J in the protocol). Enrolled participants should not receive live vaccine while receiving study intervention and up to 30 days after the last dose of IP., 14. Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of IP. Minor surgery of isolated lesions for palliative intent is acceptable if performed more than 14 days prior to the first dose of IP., 15. Prior exposure to immune-mediated therapy including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies, excluding therapeutic anticancer vaccines., 16. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion: - Intranasal, inhaled, or topical steroids or local steroid injections (eg, intra-articular injection). - Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent. - Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)., 17. Receipt of the last dose of anticancer therapy (chemotherapy, targeted therapy, biologic therapy, or mAbs) within 28 days prior to the first dose of study intervention or 5 half-lives of the anticancer therapy whichever is longer., 18. Participation in another clinical study with a study intervention administered in the last 3 months., 19. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study, or during the follow-up period of an interventional study., 2. 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, 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 hypothy

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the safety of durvalumab combined with background gemcitabine-based chemotherapy;Secondary Objective: To assess the efficacy of durvalumab combined with background gemcitabine-based chemotherapy, To further assess the safety and tolerability profile of durvalumab combined with background gemcitabine-based chemotherapy, To assess disease- and treatment-related symptoms and HRQoL;Primary end point(s): PRAE is defined as an AE which has been assessed by the investigator to be possibly related to study intervention. The measure of interest is the incidence of PRAE Grade 3 or 4 of durvalumab combined with background gemcitabine-based chemotherapy within 6 months after the initiation of durvalumab.