DURVALUMAB for Advanced biliary tract cancer

Inclusion criteria

• {"criterion_text":"- 1. Participant must be ≥ 18 years and above legal age per local regulations at the time of screening.\n- 10. Body weight of > 30 kg.\n- 11. Male or female.\n- 12. Negative pregnancy test (serum) for women of childbearing potential.\n- 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.\n- 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.\n- 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.\n- 16. Written informed consent from the participant has been obtained prior to any study-related procedures.\n- 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.\n- 2. Histologically confirmed, unresectable advanced or metastatic BTC including cholangiocarcinoma (intrahepatic or extrahepatic), gallbladder carcinoma, and AoV carcinoma\n- 3. Participants with previously untreated disease are eligible if presented with unresectable or metastatic BTC at initial diagnosis.\n- 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.\n- 5. A WHO/ECOG PS of 0 to 2.\n- 6. At least one lesion that qualifies as a RECIST 1.1 TL at baseline.\n- 7. Participants with HBV infection (as characterised by positive HBsAg and/or anti-HBcAb with detectable HBV DNA, as per local laboratory standards) must be treated with antiviral therapy, as per institutional practice, to ensure adequate viral suppression (as per local laboratory standards) prior to enrolment. Participants must remain on antiviral therapy for the study duration and for 6 months after the last dose of durvalumab. Participants who test positive for anti-HBc with undetectable HBV DNA (as per local laboratory standards) do not require antiviral therapy prior to enrolment.\n- 8. Adequate organ and marrow function, as defined below. − Haemoglobin ≥ 9 g/dL − Absolute neutrophil count ≥ 1.5 × 10*9 /L − Platelet count ≥ 100 × 10*9 /L − Serum bilirubin ≤ 2.0 × ULN; this will not apply to participants with confirmed Gilbert’s syndrome. Any clinically significant biliary obstruction should be resolved before enrolment. − ALT and AST ≤ 2.5 × ULN. For participants with hepatic metastases, ALT and AST ≤ 5 × ULN. − Calculated creatinine clearance > 50 mL/minute as determined by Cockcroft-Gault (using actual body weight) or 24-hour urine creatinine clearance. For chemotherapy regimens including carboplatin, oxaliplatin, or gemcitabine as monotherapy, the recommended threshold for calculated creatinine clearance is > 40 mL/minute as determined by Cockcroft-Gault (using actual body weight) or 24-hour urine creatinine clearance.\n- 9. Must have a life expectancy of at least 12 weeks."}

Exclusion criteria

• {"criterion_text":"- 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.\n- 10. Known allergy or hypersensitivity to any of the study intervention or any of the study intervention excipients.\n- 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.\n- 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.\n- 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.\n- 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.\n- 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.\n- 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).\n- 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.\n- 18. Participation in another clinical study with a study intervention administered in the last 3 months.\n- 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.\n- 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 hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement. − Any chronic skin condition that does not require systemic therapy. − Participants without an active disease in the last 5 years may be included. − Participants with celiac disease controlled by diet alone. − Participants with ≥ Grade 2 lymphopenia will be evaluated on a case-by-case basis.\n- 20. Prior randomisation or study intervention in a previous durvalumab clinical study, regardless of study intervention arm assignment.\n- 21. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).\n- 22. Female participants who are pregnant or breastfeeding or male or female participants of reproductive potential who are not willing to use effective 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.\n- 23. Judgement by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.\n- 3. 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 and of low potential risk for recurrence, basal cell carcinoma of the skin, squamous cell carcinoma of the skin or lentigo maligna that has undergone potentially curative therapy, or adequately treated carcinoma in situ without evidence of disease.\n- 4. History of leptomeningeal carcinomatosis.\n- 5. History of active primary immunodeficiency.\n- 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).\n- 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).\n- 8. Persistent toxicities (CTCAE Grade > 1) caused by previous anticancer therapy; alopecia and vitiligo are excluded toxicities. − Participants with Grade ≥ 1 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.\n- 9. Central nervous system metastases requiring treatment or history of 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."}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"PRAE is defined as an AE assessed by the investigator as possibly related to study intervention; the measure is the incidence of PRAE Grade 3 or 4 within 6 months after initiation of durvalumab."}

Secondary endpoints

• {"endpoint_text":"- • OS is defined as the time from the date of the first dose of study intervention until death due to any cause. The measures of interest are median OS, OS12, OS18, and OS24.","definition_or_measurement_approach":"Overall survival (OS): time from first dose to death from any cause; measures: median OS, OS at 12, 18, 24 months."}
• {"endpoint_text":"- • 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. The measure of interest is the estimate of ORR.","definition_or_measurement_approach":"Objective response rate (ORR): proportion with confirmed complete or partial response per RECIST 1.1 by investigator assessment."}
• {"endpoint_text":"- • PFS is defined as the time from the first dose of study intervention until the date of PD per RECIST 1.1 as assessed by the investigator, or death due to any cause. The measures of interest are mPFS, PFS12, and PFS18.","definition_or_measurement_approach":"Progression-free survival (PFS): time from first dose to progression per RECIST 1.1 or death; measures include median PFS and PFS at 12 and 18 months."}
• {"endpoint_text":"- • DCR is defined as the percentage of participants who have a best objective response of confirmed CR or PR by Week 24/32 or who have demonstrated SD per RECIST 1.1 for at least 24/32 weeks following the start of treatment. The measure of interest is DCR24 and DCR32.","definition_or_measurement_approach":"Disease control rate (DCR): percent with confirmed CR/PR by Week 24/32 or stable disease for at least 24/32 weeks; measures DCR at 24 and 32 weeks."}
• {"endpoint_text":"- • DOR is defined as the time from the date of first documented response until the date of documented progression per RECIST 1.1 as assessed by the investigator or death due to any cause.","definition_or_measurement_approach":"Duration of response (DOR): time from first documented response to progression per RECIST 1.1 or death."}
• {"endpoint_text":"- • DOT is defined as time on study intervention.","definition_or_measurement_approach":"Duration of treatment (DOT): time on study intervention."}
• {"endpoint_text":"- · Incidence, severity, nature, seriousness, intervention/treatment, outcome, and causality of treatment-emergent AEs, including PRAEs, AESIs, imAEs, and SAEs; AEs resulting in study intervention interruption and discontinuation; and laboratory findings · IRRs and hypersensitivity/anaphylactic reactions","definition_or_measurement_approach":"Safety endpoints: incidence, severity, seriousness, outcomes and causality of treatment-emergent AEs (including PRAEs, AESIs, immune-mediated AEs, SAEs), AEs causing interruption/discontinuation, lab findings, infusion-related and hypersensitivity reactions."}
• {"endpoint_text":"- EORTC QLQ-C30: Time to deterioration in global health status (GHS)/QoL, functioning (physical), multi-term symptom (fatigue), single-item symptoms (appetite loss, nausea). Clinically meaningful change from baseline in global health status/QoL, symptoms and function score. Best overall response for GHS/QoL, function and symptom (fatigue). Change from baseline of GHS/QoL, symptom and functioning scores at each post baseline assessment","definition_or_measurement_approach":"Patient-reported outcomes using EORTC QLQ-C30: time to deterioration and clinically meaningful changes from baseline in QoL, function, and symptoms; assessments at post-baseline visits."}
• {"endpoint_text":"- EORTC QLQ-BIL21: • Time to deterioration in single-item symptoms (abdominal pain, pruritus, and jaundice) • Clinically meaningful change from baseline (categorized as improvement, no change, or deterioration) at each post baseline assessment • Best overall response in single-item symptoms (abdominal pain, pruritus, and jaundice) • Change from baseline for each EORTC QLQ-BIL21 scale/item score at each post baseline assessment","definition_or_measurement_approach":"Patient-reported bile-tract specific outcomes using EORTC QLQ-BIL21: time to deterioration in abdominal pain, pruritus, jaundice; changes from baseline and best overall responses on these items."}

Methods

• Country-specific recruitment brochures (patient-facing) – French, Italian, Spanish versions listed in trial documents.
• Country-specific recruitment posters (patient-facing) – French, Italian, Spanish versions listed in trial documents.
• Patient Advocacy Group infogetters (materials titled 'Patient Advocacy Group Infogetter') – country-specific materials (France, Italy, Spain) indicating engagement via advocacy channels.
• Physician referral letters / 'Dear Colleague' letters (healthcare professional-facing) – e.g. 'FRA Recruitment Other Physician Referral Letter', 'ESP Recruitment Dear Colleague Letter'.
• Study infogetters / study information leaflets for patients (titled 'Study Infogetter' / 'Study Infogetter') – country-specific.
• Recruitment Procedure Description (K1) document (English) describing recruitment procedures.

Germany

Earliest CTIS Part Ii Submission Date

20-03-2024

Latest Decision Or Authorization Date

27-03-2024

Processing Time Days

7

Number Of Sites

3

Number Of Participants

12

France

Earliest CTIS Part Ii Submission Date

18-01-2024

Latest Decision Or Authorization Date

14-03-2024

Processing Time Days

56

Number Of Sites

7

Number Of Participants

19

Italy

Earliest CTIS Part Ii Submission Date

23-02-2024

Latest Decision Or Authorization Date

20-03-2024

Processing Time Days

26

Number Of Sites

4

Number Of Participants

13

Spain

Earliest CTIS Part Ii Submission Date

01-02-2024

Latest Decision Or Authorization Date

15-03-2024

Processing Time Days

43

Number Of Sites

9

Number Of Participants

32

Primary sponsor

Full Name

AstraZeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden

Contract research organisations

Name

Parexel International (IRL) Limited

Responsibilities

Sponsor duties codes: 1,10,11,12,13,2,5,6,8 (as listed in sponsorDuties)

Third parties

• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"1,10,11,12,13,2,5,6,8","organisation_type":"Pharmaceutical company"}