Observational Study Protocol: LIVER-R

Hepatobiliary Cancers Clinical Trial

— LIVER-R  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06252753
• Other study ID #: D419CR00035
• Status: Recruiting
• Start date: December 20, 2023
• Est. completion date: December 13, 2029

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 4490
• Est. completion date: December 13, 2029
• Est. primary completion date: December 13, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

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

Related Conditions & MeSH terms

• Hepatobiliary Cancers

Intervention

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).
• 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.

Locations

Country	Name	City	State
France	Research Site	Avignon	Provence-Alpes-Cote d'Azur
France	Research Site	Grenoble	Auvergne-Rhône-Alpes
France	Research Site	Marseille	Provence-Alpes-Cote d'Azur
France	Research Site	St Malo	Bretagne
France	Research Site	Strasbourg	Alsace
Germany	Research Site	Augsburg	Bavaria
Germany	Research Site	Dortmund	North Rhine-Westphalia
Germany	Research Site	Dresden	Saxony
Germany	Research Site	Hannover	Lower Saxony
Germany	Research Site	Stolberg	North Rhine-Westphalia
Greece	Research Site	Thessaloniki	Central Macedonia
Italy	Research Site	Brescia	Lombardy
Italy	Research Site	Naples	Campania
Puerto Rico	Research Site	San Juan
United States	Research Site	Canton	Ohio
United States	Research Site	Coronado	California
United States	Research Site	Gainesville	Florida
United States	Research Site	Hinsdale	Illinois
United States	Research Site	Temple	Texas

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	ICON plc

Countries where clinical trial is conducted

United States,  France,  Germany,  Greece,  Italy,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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).
Secondary	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.
Secondary	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).
Secondary	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).
Secondary	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.
Secondary	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).
Secondary	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.
Secondary	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.
Secondary	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.