Observational Study Protocol: LIVER-R (LIVER-R)

An Observational Multi Center Study to Evaluate Real World Treatment Outcomes of Durvalumab Based Regimens in Hepatobiliary Cancers

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 multicountry, multicenter, observational study of patients with a confirmed diagnosis of hepatobiliary cancer treated with 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 durvalumab-based regimens 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, and other real-world clinical endpoints (such as duration of treatment, progression-free survival, time to treatment progression, time to next treatment, recurrence-free survival, and time to treatment recurrence).

Study Overview

• Status: Recruiting
• Conditions: Hepatobiliary Cancers
• Intervention / Treatment: Other: Durvalumab-based combination therapies in observational study setting; Other: Durvalumab-based combination therapies in observational study setting

Detailed Description

LIVER-R is a real-world, multi-country, multi-centre study aiming to enroll approximately 2500 pts with unresectable hepatocellular carcinoma (uHCC; n=1135) or advanced biliary tract cancers (aBTCs; n=1355) across 22 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 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 regimen) and a follow-up period to the earliest of death, loss to follow-up, withdrawal, or end of study for a maximum follow-up of 2 years for patients with aBTCs or 3 years for patients with uHCC. 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.

• Study Type: Observational
• Enrollment (Estimated): 4490

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Germany
  • Bavaria
    • Augsburg, Bavaria, Germany, 86150
      • Recruiting
      • Research Site
  • Lower Saxony
    • Hannover, Lower Saxony, Germany, 30161
      • Recruiting
      • Research Site
  • North Rhine-Westphalia
    • Dortmund, North Rhine-Westphalia, Germany, 44137
      • Recruiting
      • Research Site
  • Saxony
    • Dresden, Saxony, Germany, 1307
      • Recruiting
      • Research Site
• Italy
  • Campania
    • Naples, Campania, Italy, 80131
      • Recruiting
      • Research Site
  • Lombardy
    • Brescia, Lombardy, Italy, 25123
      • Recruiting
      • Research Site
• United States
  • California
    • Coronado, California, United States, 92118
      • Recruiting
      • Research Site
  • Florida
    • Gainesville, Florida, United States, 32610
      • Recruiting
      • Research Site
  • Illinois
    • Hinsdale, Illinois, United States, 60521
      • Recruiting
      • Research Site
  • Ohio
    • Canton, Ohio, United States, 44718
      • Recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population includes patients treated with a durvalumab based regimen for hepatobiliary cancer as part of routine clinical practice. The decision to treat patients with a durvalumab based regimen should be independent from the decision to enroll patients in the study. Depending on the country, it is anticipated that 15 to 400 patients may be enrolled in each participating country.

Description

Inclusion Criteria:

1. Age ≥18 years and a lawful adult in the country at the index date
2. Confirmed presence of malignancy of primary hepatobiliary cancer (i.e., uHCC or aBTC) by the treating physician
3. Type of hepatobiliary cancer indication is approved to be treated (i.e., positive phase 3 clinical trial read out for HIMALAYA or TOPAZ 1) with a durvalumab based regimen in the respective country or was administered as part of an EAP
4. Informed consent was obtained as per country level regulations on or after the index date

Exclusion Criteria:

1. 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
2. Received other systemic therapies for hepatobiliary cancer indication on or after diagnosis date through the index date (e.g., uHCC or aBTC patient who received a systemic treatment for unresectable HCC or advanced BTC, respectively, prior to initiating durvalumab based regimen)
3. Received a liver transplant during the baseline period

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
unresectable hepatocellular carcinoma (uHCC)	Other: Durvalumab-based combination therapies in observational study setting; Data on patients who initiated durvalumab-based regimens, including STRIDE (Single Tremelimumab Regular Interval Durvalumab), will be collected).; Other Names: Imfinzi; Other: Durvalumab-based combination therapies in observational study setting; Data on patients who initiated durvalumab-based regimens, including durvalumab + chemotherapy combinations (e.g., Durvalumab + GemCis etc.) will be collected.; Other Names: Imfinzi
advanced biliary tract cancer (aBTC)	Other: Durvalumab-based combination therapies in observational study setting; Data on patients who initiated durvalumab-based regimens, including STRIDE (Single Tremelimumab Regular Interval Durvalumab), will be collected).; Other Names: Imfinzi; Other: Durvalumab-based combination therapies in observational study setting; Data on patients who initiated durvalumab-based regimens, including durvalumab + chemotherapy combinations (e.g., Durvalumab + GemCis etc.) will be collected.; Other Names: Imfinzi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Real-world overall survival (rwOS)	rwOS will be calculated as the time from the index date to date of death, by any cause.	rwOS will be assessed as OS rates at 6, 12, 24 months (both aBTC and uHCC), and 36 months (uHCC), median OS for a maximum follow-up of 2 and 3 years for aBTC and uHCC, respectively.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Real-world duration of treatment (rwDOT)	rwDOT will be calculated for each systemic treatment as the time from the index date to date of discontinuation for any reason.	rwDOT will be assessed as median DOT for a maximum follow-up of 2 years (aBTC) or 3 years (uHCC).
Real-world progression free survival (rwPFS)	rwPFS will be calculated as the time from the index date to the date of documented disease progression as determined by the physician's assessment or death, whichever is earlier.	rwPFS will be assessed as PFS rates at 6, 12, 24 months (both aBTC and uHCC), and 36 months (uHCC), median PFS for a maximum follow-up of 2 and 3 years for aBTC and uHCC, respectively.
Real-world time to progression (rwTTP)	rwTTP will be calculated as the time from the index date to the date of documented disease progression as determined by the physician's assessment.	rwTTP will be assessed as median TTP for a maximum follow-up of 2 years (aBTC) or 3 years (uHCC).
Real-world time to next treatment (rwTTNT)	rwTTNT will be calculated as the time from the index date to the date of initiation of the next treatment.	rwTTNT will be assessed as median TTNT for a maximum follow-up of 2 years (aBTC) or 3 years (uHCC).
Real-world recurrence free survival (rwRFS)	rwRFS will be defined as the time from the index date to the date of documented disease recurrence as determined by the physician's assessment or death, whichever is earlier. The analysis will be performed in patients who underwent curative therapy (resection or ablation).	rwRFS will be assessed as RFS rates at 6, 12, 24 months (both aBTC and uHCC), and 36 months (uHCC), median RFS for a maximum follow-up of 2 and 3 years for aBTC and uHCC, respectively.
Real-world time to recurrence (rwTTR)	rwTTR will be defined as the time from the index date to the date of documented disease recurrence as determined by the physician's assessment. The analysis will be performed in patients who underwent curative therapy (resection or ablation).	rwTTR will be assessed as median TTR for a maximum follow-up of 2 years (aBTC) or 3 years (uHCC).
Patient demographic and clinical characteristics	Descriptive statistics will be used to describe demographic and clinical characteristics for the enrolled patients.	Patient demographic and clinical characteristics will be captured up to 5 years prior to the index date.
Percentage of patients receiving each treatment regimen	Treatment patterns will be calculated from the index date until death, loss to follow-up, withdrawal from the study, or end of the study, whichever is earliest.	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 maximum follow-up of 2 years for patients with aBTCs or 3 years for patients with uHCC.
Clinically significant events (CSEs) of interest leading to a medical intervention	CSEs of interest leading to medical intervention including durvalumab based treatment interruption, discontinuation, hospitalization, or which require interventions of concomitant use of corticosteroids, immunosuppressants and/or endocrine therapies will be captured for the enrolled patients.	CSEs will be captured from the index date through 90 days after the last administration of durvalumab-based regimen or death, whichever occurs first.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: ICON plc

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2023
• Primary Completion (Estimated): December 13, 2029
• Study Completion (Estimated): December 13, 2029

Study Registration Dates

• First Submitted: December 21, 2023
• First Submitted That Met QC Criteria: February 1, 2024
• First Posted (Actual): February 12, 2024

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Durvalumab; Real-world; Hepatobiliary cancer; Observatory; Unresectable hepatocellular carcinoma (uHCC); Advanced biliary tract cancer (aBTC)
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Durvalumab; Antibodies, Monoclonal
• Other Study ID Numbers: D419CR00035

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Plan to share only the redacted CSR synopsis
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No