An Observational Multi-Center Study to Evaluate Real-World Treatment Outcomes With or Without Durvalumab-Based Regimens in Hepatobiliary Cancers
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 4,000
- 试验地点
- 160
- 主要终点
- Real-world overall survival (rwOS) in all participants
研究概览
简要总结
Given the number of anticipated durvalumab-based treatment launches in the hepatobiliary cancer space over the next 3 years, there is a need to capture contemporary real-world data across these indications. LIVER-R is a multi-country, multi-center, observational study of patients with a confirmed diagnosis of hepatobiliary cancer treated with or without a durvalumab-based regimen as part of routine clinical practice or early access program (EAP). The study design will include primary and secondary data collection. The primary objective of this study is to evaluate the effectiveness of regimens (durvalumab-based or otherwise) in real-world settings as measured by real-world overall survival. Other endpoints include demographics, clinical characteristics, clinically significant events of interest, treatment patterns, concomitant medications, treatment provider characteristics, and other real-world clinical endpoints (such as duration of treatment, progression-free survival, time to treatment progression, time to next treatment, time to treatment discontinuation, recurrence-free survival, and time to treatment recurrence ).
详细描述
LIVER-R is a real-world, multi-country, multi-centre study aiming to enroll approximately 4,000 patients across hepatobiliary cohorts (approximately 1,385 patients for aBTC, approximately 1,165 patients for uHCC, approximately 1,000 patients for eeHCC, and approximately 400 patients for EMERALD) across multiple countries from North and South America, Europe, the Middle East and the Asia-Pacific region. The study design will include primary and secondary data collection. Primary data will be collected in real-time during the patient's routine visit. Secondary data will be collected from the patient's medical record at enrollment and at prespecified study time points (6-month intervals). The study population includes adult patients whose physician has previously made the decision to treat them with or without a durvalumab-based regimen for hepatobiliary cancer as part of routine clinical practice or patients receiving treatment through EAP. The study will include a baseline period of up to 5 years before the index date (initiation of a durvalumab-based or non durvalumab-based regimen) and a follow-up period to the earliest of death, loss to follow-up, withdrawal, or end of study for a minimum follow-up of 2 years. This is a descriptive, noncomparative study. No formal hypotheses are to be tested. All descriptive analyses will be conducted separately for each primary hepatobiliary cancer indication. Kaplan Meier estimates will be produced for time-to-event outcomes.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
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
- •General Inclusion Criteria
- •All patients must meet all of the following general criteria 1-4 along with all respective cohort specific criteria noted below:
- •Age ≥18 years and a lawful adult in the country at the index date
- •Confirmed presence of malignancy of primary hepatobiliary cancer by any method (e.g., radiological, histological, etc.)
- •Decision to treat was made independently and prior to obtaining informed consent
- •Informed consent was obtained as per country level regulations (includes waiver of consent for retrospective data collection if approved)
- •aBTC Specific Inclusion Criteria
- •A patient will be eligible to be included in the aBTC cohort if they meet all general inclusion criteria 1-4 in addition to the following criteria:
- •Patient has unresectable aBTC
- •Has received or is intending to receive a durvalumab-based regimen (may have been treated in an EAP)
- •uHCC Specific Inclusion Criteria
- •A patient will be eligible to be included in the uHCC cohort if they meet all general inclusion criteria 1-4 in addition to the following criteria:
- •Patient has unresectable uHCC
- •Not eligible for LRT, as well as for those who progressed following LRT
- •Has received or is intending to receive a durvalumab-based regimen (may have been treated in an EAP)
- •eeHCC Specific Inclusion Criteria
- •A patient will be eligible to be included in the eeHCC cohort if they meet all general inclusion criteria 1-4 in addition to the following criteria:
- •HCC confirmed by radiological or histological diagnosis
- •Child-Pugh A-B7
- •Disease not amenable to curative treatment but amenable to LRT at index
- •Patients with liver-confined HCC who initiated first non-curative intent LRT on or after 01 January 2024
- •Patients eligible for LRT with palliative intent such as TACE/ TARE/transarterial infusion chemotherapy (TAIC)/ hepatic arterial infusion chemotherapy (HAIC)/transarterial embolization (TAE) given by itself or in combination with other systemic therapy (can include durvalumab) within 60 days of the LRT
- •EMERALD Specific Inclusion Criteria
- •A patient will be eligible to be included in the EMERALD cohort if they meet all general inclusion criteria 1-4 in addition to the following criteria:
- •HCC confirmed by radiological or histological diagnosis
- •Child-Pugh score of A-B7
- •Liver-confined disease not amenable to curative treatment but amenable to LRT at index
- •Receipt of a durvalumab-based regimen in combination with LRT administered within 28 days of each other (index is the first of the two treatments administered)
排除标准
- •General Exclusion Criteria
- •A patient will be excluded from participating in this study if they meet any of the following general criteria 1-2 or any cohort specific exclusion criteria:
- •Currently/was participating or plans to participate in any clinical trial for investigational treatment for hepatobiliary cancers on or after the diagnosis date until the index date
- •Second primary malignancy prior to HCC or BTC diagnosis
- •aBTC Specific Exclusion Criteria
- •A patient will be excluded from participating in the aBTC cohort if they meet any of the general exclusion criteria 1-2 or any of the following criteria:
- •Received a liver transplant during the baseline period
- •Received more than 1 cycle of Gemcitabine + Cisplatin for biliary tract cancer on or after diagnosis of unresectable, locally advanced or metastatic disease through the index date. Patients who received any systemic therapy while having early stage, resectable disease are eligible
- •uHCC Specific Exclusion Criteria
- •A patient will be excluded from participating in the uHCC cohort if they meet any of the general exclusion criteria 1-2 or any of the following criteria:
- •Received a liver transplant during the baseline period
- •Received other systemic therapies for hepatobiliary cancer indication on or after diagnosis date through the index date
- •eeHCC Specific Exclusion Criteria
- •A patient will be excluded from participating in the eeHCC cohort if they meet any of the general exclusion criteria 1-2 or any of the following criteria:
- •Eligible for curative therapy at the time of receiving LRT (ablation)
- •Extrahepatic spread
- •Portal vein tumor thrombosis (PVTT) of VP3/4
- •Receipt of systemic therapy prior to index LRT in the baseline period
- •Liver transplant any time prior to index
- •EMERALD Specific Exclusion Criteria
- •A patient will be excluded from participating in the EMERALD cohort if they meet any of the general exclusion criteria 1-2 or any of the following criteria:
- •Eligible for curative therapy at the time of receiving LRT (ablation)
- •Extrahepatic spread
- •Portal vein tumor thrombosis (PVTT) of VP3/4
- •Receipt of systemic therapy prior to index LRT in the baseline period
- •Liver transplant any time prior to index
研究组 & 干预措施
unresectable hepatocellular carcinoma (uHCC)
advanced uHCC patients who had not received prior systemic therapy and were not eligible for LRT, as well as those who had progressed following LRT, and who have received a durvalumab-based regimen
干预措施: Durvalumab-based combination therapies in observational study setting (Other)
EMERALD
uHCC patients with liver-confined disease not amenable to curative treatment but amenable to LRT who receive durvalumab-based regimens in combination with LRT (durvalumab and LRT are given within 28 days of each other, regardless of order)
干预措施: Durvalumab-based combination therapies in observational study settings (Other)
advanced biliary tract cancer (aBTC)
patients with advanced BTC (aBTC) who are not eligible for resection and who have received a durvalumab-based regimen
干预措施: Durvalumab-based combination therapies in observational study setting (Other)
eeHCC
uHCC patients with liver-confined disease not amenable to curative treatment but amenable to LRT who receive LRT alone or LRT followed by systemic therapy within 60 days (if administered in combination, LRT must be received first)
干预措施: Non Durvalumab-based therapies in observational study setting (Other)
结局指标
主要结局
Real-world overall survival (rwOS) in all participants
时间窗: rwOS will be assessed as OS rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median OS for a minimum follow-up of 2 years.
rwOS will be calculated as the time from the index date to date of death, by any cause.
次要结局
- Clinically significant events (CSEs) of interest leading to a medical intervention in all participants(CSEs will be captured from the index date through 90 days after the last administration of durvalumab-based or non durvalumab-based regimens or death, whichever occurs first.)
- Patient demographic and clinical characteristics in all participants(Patient demographic and clinical characteristics will be captured up to 5 years prior to the index date.)
- Characterize the durvalumab-based regimen and/or LRT treatment patterns in all participants(Treatment patterns will be captured from the index date until the earliest of death, loss to follow-up, withdrawal, or end of study for a minimum follow-up of 2 years.)
- Real-world duration of treatment (rwDOT) in all participants(rwDOT will be assessed as event rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median DOT for a minimum follow-up of 2 years.)
- Real-world progression free survival (rwPFS) in all participants(rwPFS will be assessed as PFS rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median PFS for a minimum follow-up of 2 years.)
- Real-world time to progression (rwTTP) in all participants(rwTTP will be assessed as event rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median TTP for a minimum follow up of 2 years.)
- Real-world time to next treatment (rwTTNT) in all participants(rwTTNT will be assessed as event rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median TTNT for a minimum follow-up of 2 years.)
- Real-world time to treatment discontinuation (rwTTD) in all participants(rwTTD will be assessed as event rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median TTD for a minimum follow-up of 2 years.)
- Characterization of providers among all participants(Provider characteristics will be captured up to 5 years prior to the index date)
- Real-world recurrence free survival (rwRFS) in aBTC and uHCC(rwRFS will be assessed as RFS rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median RFS for a minimum follow-up of 2 years.)
- Real-world time to recurrence (rwTTR) in aBTC and uHCC(rwTTR will be assessed as recurrence rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median TTR for a minimum follow-up of 2 years.)
- Liver function over time in eeHCC and EMERALD(Liver function will be assessed as the change in liver function markers for a minimum follow-up of 2 years)
- Provider specialty and treatment patterns in eeHCC(Provider specialty will be assessed descriptively and treatment patterns will be assessed as a percentage of participants for a minimum follow-up of 2 years)
- Clinical characteristics in EMERALD and eeHCC(Clinical characteristics will be assessed descriptively for a minimum follow-up of 2 years.)