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)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 142
- 试验地点
- 34
- 主要终点
- Number of participants with Grade 3 or 4 possibly related adverse event (PRAE)
研究概览
简要总结
A study to assess the safety and efficacy of durvalumab in combination with gemcitabine-based chemotherapy regimens in participants with aBTC.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Durvalumab + Gemcitabine based chemotherapy
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.
干预措施: Gemcitabine + oxaliplatin (Drug)
Durvalumab + Gemcitabine based chemotherapy
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.
干预措施: Gemcitabine + carboplatin (Drug)
Durvalumab + Gemcitabine based chemotherapy
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.
干预措施: Durvalumab (Biological)
Durvalumab + Gemcitabine based chemotherapy
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.
干预措施: Gemcitabine monotherapy (Drug)
Durvalumab + Gemcitabine based chemotherapy
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.
干预措施: Gemcitabine + S-1 (Drug)
Durvalumab + Gemcitabine based chemotherapy
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.
干预措施: Gemcitabine + cisplatin + albumin-bound paclitaxel (Drug)
Durvalumab + Gemcitabine based chemotherapy
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.
干预措施: Gemcitabine + cisplatin (Drug)
Durvalumab + Gemcitabine based chemotherapy
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.
干预措施: Gemcitabine + cisplatin + S-1 (Drug)
结局指标
主要结局
Number of participants with Grade 3 or 4 possibly related adverse event (PRAE)
时间窗: Within 6 months after the initiation of Investigational Medicinal Product (IMP)
PRAE is defined as an AE which has been assessed by the investigator to be possibly related to IMP.
次要结局
- 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])
- Overall Survival (OS)(From the date of the first dose of IMP until death due to any cause [approx. upto 33 months])
- 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])
- 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])
- 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])
- Disease Control Rate (DCR)(Week 24 and Week 32)
- 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])
- 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])
- 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])
- 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])