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

• 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: CTIS2022-502043-35-00
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-05-09
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. Participant must be = 18 years 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 of the background gemcitabine-based chemotherapy, 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 using an acceptable method of contraception (see Appendix H in the protocol) 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 of the background gemcitabine-based chemotherapy, 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 Genetic Research Information informed consent prior to collection of sample for optional genetic 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,

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., 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., 6. Known to have tested positive for HIV (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice)., 20. Prior randomisation or study intervention in a previous durvalumab clinical study, regardless of study intervention arm assignment., 21. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)., 7. Participants co-infected with HBV (presence of HBsAg and/or anti-HBcAb with detectable HBV DNA, as per local laboratory standards) and HCV (presence of anti-HCV antibodies), or coinfected with HBV and HDV (presence of anti-HDV antibodies)., 8. Persistent toxicities (CTCAE Grade > 1) caused by previous anticancer therapy; alopecia and vitiligo are excluded toxicities. ? Participants with Grade = 2 neuropathy will be evaluated on a case-by-case basis. ? Participants with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab in the opinion of the Investigator may be included., 9. History of, or current, brain metastases or spinal cord compression (including asymptomatic and adequately treated disease). Participants with suspected brain metastases at screening should have an MRI (preferred) or CT scan, each preferably with IV contrast of the brain prior to study entry., 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., 10. Known allergy or hypersensitivity to any of the study intervention or any of the study intervention excipients., 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

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.