Lenvatinib Combined With PD-1 Inhibitors as First-line Treatment for Unresectable/Advanced Biliary Tract Carcinoma (LEADER-001)

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

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)

Study Overview

• Status: Recruiting
• Conditions: Biliary Tract Cancer
• Intervention / Treatment: Drug: Lenvatinib; Drug: PD-1 inhibitors

• Study Type: Interventional
• Enrollment (Anticipated): 46
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: liu bo, master; Phone Number: 15844057274; Email: liuboliubo1109@163.com

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China, 130021
      • Recruiting
      • Liu Bo
      • Contact: liu bo, master; Phone Number: 15844057274; Email: liuboliubo1109@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients had good compliance, understood the study procedure, and signed written informed consent
2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 2, Patients cannot tolerate chemotherapy or refuse to receive chemotherapy for any reason.
3. Pathologically or cytologically confirmed biliary tract cancer
4. Patients who are advanced and/or unresectable after imaging and multidisciplinary consultation
5. Patients must have at least one measurable lesion as defined by RECIST 1.1
6. Survival expectation of 12 weeks or longer after beginning of study treatment

7. 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

8. Patients requiring biliary stent implantation must complete the procedure at least 14 days before enrollment

Exclusion Criteria:

1. Allergy to Lenvatinib or PD-1 inhibitors
2. Patients who have had other malignancies within the past 2 years (except cured carcinoma in situ and basal cell carcinoma of the skin)
3. 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
4. Patients with ampullary carcinoma are excluded (patients with mixed HCC/ BTC may be considered)
5. 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
6. Major surgery prior to initiation of the study intervention and insufficient recovery from surgery and/or surgical complications
7. 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)
8. Patients after organ transplantation
9. Known to have active tuberculosis (TB: tubercle bacilli)
10. Complete or incomplete intestinal obstruction
11. 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;
12. Patients considered unsuitable for study judged by the researcher

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Lenvatinib+PD-1 inhibitors; 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; 8 mg once daily (QD) oral dosing.; Other Names: E7080, Lenvima; Drug: PD-1 inhibitors; Regular dose intravenously every 3 weeks

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The First Hospital of Jilin University

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 20, 2022
• Primary Completion (ANTICIPATED): February 1, 2023
• Study Completion (ANTICIPATED): September 1, 2023

Study Registration Dates

• First Submitted: August 18, 2022
• First Submitted That Met QC Criteria: August 18, 2022
• First Posted (ACTUAL): August 22, 2022

Study Record Updates

• Last Update Posted (ACTUAL): September 10, 2022
• Last Update Submitted That Met QC Criteria: September 8, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Biliary Tract Cancer; lenvatinib; PD-1 inhibitors
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Biliary Tract Diseases; Biliary Tract Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Lenvatinib; Immune Checkpoint Inhibitors
• Other Study ID Numbers: FirstJlinU

Drug and device information, study documents

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