Clinical trial NCT06648057: Investigation of Predictive Biomarkers in Patients With Advanced BTC Treated With Lenvatinib Plus Pembrolizumab
Official title: Investigation of Predictive Biomarkers in Patients With Advanced Biliary Tract Cancer Treated With Lenvatinib Plus Pembrolizumab
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Biliary Tract Cancer
Cholangiocarcinoma
Keywords: Lenvatinib
Pembrolizumab
Biliary Tract Cancer
Biomarker
RNA sequencing
Lead sponsor: CHA University
Sponsor class: OTHER
First posted: 2024-10-18
Enrollment: 100
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with Advenced Biliary Tract Cancer will be recruited at CHA Bundang Medical Center

Brief summary: The goal of this observational study is to evaluate the clinical efficacy and safety of lenvatinib plus pembrolizumab combination therapy in patients with advanced biliary tract cancer (BTC). This study aims to identify potential biomarkers that may predict treatment response by analyzing genetic data from blood and tissue samples. The study will focus on real-world clinical outcomes and the exploratory discovery of biomarkers associated with the efficacy of this treatment regimen.

Detailed description: Biliary tract cancers (BTCs) have a higher prevalence in Asia compared to Western countries, with South Korea ranking second globally in BTC incidence. According to data from the Central Cancer Registry in 2023, the 5-year survival rate for BTC from 2017 to 2021 was 28.9%, significantly lower than other cancers such as gastric cancer (77.9%), colorectal cancer (74.3%), and breast cancer (93.8%).

Surgery is the primary treatment for BTC, but only 40-50% of patients are eligible for curative resection. For patients with unresectable, advanced, or metastatic BTC, the standard first-line treatment has been gemcitabine plus cisplatin (GP) since the results of the ABC-02 Phase 3 trial in 2010. Recently, two Phase 3 trials-TOPAZ-1 in 2022 and KEYNOTE-966 in 2023-demonstrated significant survival benefits with the addition of immune checkpoint inhibitors (durvalumab or pembrolizumab) to GP therapy, establishing these combination regimens as the new first-line standard treatment for advanced BTC. These combinations have been approved for use in South Korea.

However, for patients who fail first-line GP therapy, the most commonly selected second-line treatment, FOLFOX (5-FU + leucovorin + oxaliplatin), offers only a modest survival extension of about one month compared to supportive care. This highlights the clinical unmet need for more effective second-line treatments. A multicenter Phase 2 trial has demonstrated the efficacy of lenvatinib plus pembrolizumab as a promising treatment option for these patients.

This prospective observational study aims to evaluate the clinical efficacy and safety of lenvatinib plus pembrolizumab combination therapy in real-world clinical practice for advanced BTC. Additionally, the study seeks to explore potential predictive biomarkers through genetic analyses of blood and tissue samples to better understand which patients are most likely to benefit from this treatment.

Eligibility criteria: Inclusion Criteria:

* Patients with histologically or cytologically confirmed advanced biliary tract cancer.
* Patients scheduled to receive Lenvatinib + Pembrolizumab for the treatment of advanced biliary tract cancer.
* ECOG performance status of 0-2.
* Patients aged 20 years or older at the time of treatment initiation.
* Patients who understand and consent to participate in this study, and agree to provide samples obtained during the examination process.

Exclusion Criteria:

* Patients who do not consent to participate in the study or withdraw their consent.

Primary outcomes:
measure: collected tumor samples
timeFrame: through study competition, an average of 2 years
measure: Collected Blood Samples
timeFrame: Through study completion, an average of 2 years
Secondary outcomes:
measure: Multi-Omics Analysis for Therapeutic Target Identification
timeFrame: Through study completion, an average of 2 years.
measure: Biomarkers on the Efficacy of Lenvatinib and Pembrolizumab for Advanced Biliary Tract Cancer
timeFrame: Through study completion, an average of 2 years.
Other outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Through study completion, an average of 2 years.
measure: Overall Survival (OS)
timeFrame: Through study completion, an average of 2 years.
measure: Objective Response Rate (ORR)
timeFrame: Through study completion, an average of 2 years.
measure: Incidence of Adverse Events (AEs)
timeFrame: Through study completion, an average of 2 years.
Locations:
city: Seongnam-si
country: Korea, Republic of
facility: Bundang CHA Medical Center
state: Gyeonggi-do
Study officials:
affiliation: CHA University
name: Hong Jae Chon, MD. PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273-81. doi: 10.1056/NEJMoa0908721.
citation: Oh DY, Ruth He A, Qin S, Chen LT, Okusaka T, Vogel A, Kim JW, Suksombooncharoen T, Ah Lee M, Kitano M, Burris H, Bouattour M, Tanasanvimon S, McNamara MG, Zaucha R, Avallone A, Tan B, Cundom J, Lee CK, Takahashi H, Ikeda M, Chen JS, Wang J, Makowsky M, Rokutanda N, He P, Kurland JF, Cohen G, Valle JW. Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer. NEJM Evid. 2022 Aug;1(8):EVIDoa2200015. doi: 10.1056/EVIDoa2200015. Epub 2022 Jun 1.
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