Lenvatinib Combined With PD-1 Inhibitors as First-line Treatment for Unresectable/Advanced Biliary Tract Carcinoma

Study Overview
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Brief Summary
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This is a multi-center, single-arm,phase Ⅱ study to evaluate the efficacy and safety of Lenvatinib in combination with PD-1 inhibitors as first-line treatment in patients with unresectable advanced Biliary Tract Carcinoma (BTC)

Official Title
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Lenvatinib Combined With PD-1 Inhibitors as First-line Treatment for Unresectable/Advanced Biliary Tract Carcinoma：a Multicenter,Single-arm,Phase II Study

Conditions
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Biliary Tract Cancer

Intervention / Treatment
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* Drug: Lenvatinib
* Drug: PD-1 inhibitors


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients had good compliance, understood the study procedure, and signed written informed consent Eastern Cooperative Oncology Group (ECOG) Performance Status of 2, Patients cannot tolerate chemotherapy or refuse to receive chemotherapy for any reason. Pathologically or cytologically confirmed biliary tract cancer Patients who are advanced and/or unresectable after imaging and multidisciplinary consultation Patients must have at least one measurable lesion as defined by RECIST 1.1 Survival expectation of 12 weeks or longer after beginning of study treatment The major organs meeting the following criteria: Adequate bone marrow function,defined as: Hemoglobin (HGB) ≥80g/L;Neutrophil absolute count (ANC) ≥1.0×10^9/L;Platelet (PLT) ≥60×10^9/L Adequate liver function, defined as: aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≤ 2.5× upper limit of normal (ULN) ( ≤ 5.0 × ULN for participants with the liver transplantion);Serum total bilirubin（STB） <1.5×ULN Adequate renal function ，defined as：Serum creatinine was within 1.5 times the normal range Patients requiring biliary stent implantation must complete the procedure at least 14 days before enrollment Exclusion Criteria: Allergy to Lenvatinib or PD-1 inhibitors Patients who have had other malignancies within the past 2 years (except cured carcinoma in situ and basal cell carcinoma of the skin) Patients who have previously received systemic therapy, except for permitted neoadjuvant/adjuvant therapy, neoadjuvant/adjuvant therapy should be completed at least 4 months before diagnosis of advanced and/or unresectable disease Patients with ampullary carcinoma are excluded (patients with mixed HCC/ BTC may be considered) Active autoimmune disease requiring systemic treatment (i.e. corticosteroids or immunosuppressive drugs) within the past 2 years.Alternative therapies (e.g., thyroxine, insulin, or physical corticosteroid replacement for adrenal or pituitary insufficiency) are not considered systemic and permitted Major surgery prior to initiation of the study intervention and insufficient recovery from surgery and/or surgical complications Radiation therapy was received within 2 weeks prior to initiation of study therapy. Or the subject must have recovered from all radiation-related toxicity, not required corticosteroids, and have not experienced radiation pneumonia; Palliative radiotherapy for non-central nervous system (CNS) disease (≤2 weeks) allows a washout period of 1 week (if deemed safe by the investigator) Patients after organ transplantation Known to have active tuberculosis (TB: tubercle bacilli) Complete or incomplete intestinal obstruction Have serious comorbidities that may affect study administration or evaluation of study results, such as HIV positive, active chronic HBV/HCV, clinically severe (i.e., active) heart disease, uncontrolled epilepsy, central nervous system disease, or psychiatric disorders; Patients considered unsuitable for study judged by the researcher

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lenvatinib+PD-1 inhibitors<br>Participants received lenvatinib capsules 8 mg , orally, once daily (QD) PD-1 inhibitors in this study include, but not limited to, Pembrolizumab, nivolumab, sintilimab, toripalimab, etc. The usage and dosage refer to label information or other clinical study | Drug: Lenvatinib<br>* 8 mg once daily (QD) oral dosing.<br>* Other names: E7080, Lenvima;Drug: PD-1 inhibitors<br>* Regular dose intravenously every 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | ORR was assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. ORR was defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR). Confirmation of CR or PR was performed at least 28 days following the initial achievement of the response | 12-months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate (DCR) | DCR was assessed by the investigator based on RECIST 1.1. DCR was defined as the percentage of participants whose BOR was CR, PR or SD | 12-months | 
| Progression-free Survival (PFS) | PFS was assessed by the investigator based on RECIST 1.1. PFS was defined as the time from the date of first dose to the date of last documentation of disease progression or date of death from any cause, whichever occurred first. For participants who did not have an event, PFS were censored. PFS was calculated using Kaplan-Meier method | 12-months | 
| Overall Survival (OS) | OS was defined as the time from the date of first dose to the date of death from any cause. For the participants who were alive or unknown, OS was censored on the last date participant was known to be event-free or date of data-cut-off. OS was calculated using the Kaplan-Meier method. | 24-months | 
| Overall Survival (OS) Rate at 9 months | OS was defined as the time from the date of first dose to the date of death from any cause. For the participants who were alive or unknown, OS was censored on the last date participant was known to be event-free or date of data-cut-off. | 9-months | 
| Overall Survival (OS) Rate at 12 months | OS was defined as the time from the date of first dose to the date of death from any cause. For the participants who were alive or unknown, OS was censored on the last date participant was known to be event-free or date of data-cut-off. | 12-months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lenvatinib, Biliary Tract Cancer, PD-1 inhibitors