Combined Therapy Using Gemcitabine and Cisplatin Chemotherapy, Lenvatinib and Adebrelimab for Patients With Advanced and Unresectable Intrahepatic Cholangiocarcinoma

Combined Therapy Using Gemcitabine and Cisplatin Chemotherapy, Lenvatinib and Adebrelimab for Patients With Advanced and Unresectable Intrahepatic Cholangiocarcinoma: a Prospective, Single-arm, Phase II Trial.

In this phase 2 study, the investigators aim to evaluate the efficacy and safety of combined therapy using gemcitabine and cisplatin chemotherapy, Lenvatinib and Adebrelimab for patients with advanced and unresectable intrahepatic cholangiocarcinoma

Study Overview

• Status: Recruiting
• Conditions: Intrahepatic Cholangiocarcinoma
• Intervention / Treatment: Drug: combined therapy using gemcitabine and cisplatin chemotherapy, Lenvatinib and Adebrelimab

Detailed Description

Most intrahepatic cholangiocarcinoma (ICC) patients are often accompanied by local or distant metastases and lose the opportunity for surgical resection. For patients with unresectable ICC who have been in stages IIIb and IV (AJCC/UICC, V2, 2018), the survival time is less than 4 months, and there is currently no standard treatment. TheGC chemotherapy (gemcitabine and cisplatin) has been used in the treatment of advanced intrahepatic cholangiocarcinoma, but the efficacy is still unsatisfactory. Lenvatinib is a small molecule multi-kinase inhibitor, the main targets including VEGFR1-3, fibroblast growth factor receptor 1-4, PDGFRα, RET(ret proto-oncogene ), KIT(KIT proto-oncogene, receptor tyrosine kinase), have anti-angiogenic effects, have been proven effective in hepatocellular carcinoma. In recent years, immunological checkpoint inhibitors (ICIs) have shown remarkable therapeutic effects in the treatment of various solid tumors. Combined with other therapies such as chemotherapy and targeted drugs is an important direction to improve the therapeutic effect of immunological checkpoint inhibitors. In this study, the investigators aim to evaluate the efficacy and safety of GC chemotherapy combined with Lenvatinib and immune checkpoint inhibitor PD-L1 antibody Adebrelimab for patients with advanced and unresectable intrahepatic cholangiocarcinoma.

• Study Type: Interventional
• Enrollment (Estimated): 38
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mengya Zang; Phone Number: 86-20-62787430; Email: zangmy@163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • Nanfang Hospital of Southern Medical University
      • Contact: Mengya Zang; Phone Number: 86-20-62787430; Email: zangmy@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. The patient must be required to sign an informed consent form;
2. Age 18-75 years old, male or female;
3. Eastern Cooperative Oncology Group (ECOG) fitness status score (PS score) 0-1;
4. Child-Pugh score A;
5. Histopathologically confirmed intrahepatic cholangiocarcinoma; consent to provide previously stored tumor tissue specimens or fresh biopsy tumor lesions;
6. Advanced and unresectable ICC patients;
7. The expected survival is longer than 12 weeks;
8. At least 1 measurable liver lesion or non-liver lesion (according to RECIST 1.1);
9. Functional indicators of vital organs meet the following requirements a Neutrophils ≥1.5*109/L; platelets≥100*109/L; hemoglobin≥9g/dl; serum albumin≥3g/dl; b Thyroid stimulating hormone (TSH) ≤ 1 times the upper limit of normal value(ULN), T3, T4 are in the normal range; c bilirubin ≤ 2 times ULN; Alanine aminotransferase （ALT） and Aspartate aminotransferase （AST） ≤ 2 times ULN; serum creatinine ≤ 1.5 ULN, creatinine clearance rate ≥ 60ml / min;
10. Non-lactating or pregnant women, contraception during or after 3 months of treatment.

Exclusion Criteria:

1. Pathological diagnosis of hepatocellular carcinoma, mixed liver cancer and other non-cholangiocarcinoma malignant tumor components;
2. Patients who have received previous treatment with PD1 antibody, programmed death ligand -1 （PD-L1） antibody or cytotoxic T lymphocyte-associated antigen-4 （CTLA4） antibody;
3. With other malignant tumors, except for fully treated non-melanoma skin cancer, cervical carcinoma in situ, and papillary thyroid carcinoma;
4. Active tuberculosis infection. Patients with active tuberculosis infection within 1 year prior to enrollment; had a history of active tuberculosis infection more than 1 year before enrollment, did not receive formal anti-tuberculosis treatment or tuberculosis is still active;
5. Have an active, known or suspected autoimmune disease. Subjects who require only hormone replacement therapy for hypothyroidism and skin diseases that do not require systemic therapy may be enrolled;
6. Previous interstitial lung disease, or (non-infectious) pneumonia and need oral or intravenous steroid therapy;
7. Long-term systemic hormones (dose equivalent to >10 mg prednisone/day) or any other form of immunosuppressive therapy are required. Subjects using inhaled or topical corticosteroids may be enrolled;
8. Severe cardiopulmonary and renal dysfunction;
9. Suffering from high blood pressure, and can not be well controlled by antihypertensive drugs (systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg);
10. Abnormal blood coagulation (PT>14s), with bleeding tendency or receiving thrombolytic or anticoagulant therapy;
11. Hepatitis B virus （HBV） DNA>2000 copies/ml, hepatitis C virus （HCV） RNA>1000;
12. Significant clinically significant bleeding symptoms or a clear tendency to appear within 6 months prior to enrollment;
13. Active infections requiring systemic treatment;
14. Human immunodeficiency virus (HIV) positive;
15. History of psychotropic substance abuse, alcohol abuse or drug abuse;
16. Has a history of allergy to platinum;
17. Other factors that may influence the safety of the subject or the compliance of the test by the investigator. Serious illnesses (including mental illness), severe laboratory tests, or other family or social factors that require combined treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combined therapy using GC, Lenvatinib and Adebrelimab; GC chemotherapy every 3 weeks,with a total of 6 cycles. Lenvatinib 8 mg once daily (QD) oral dosing. Adebrelimab 1200mg intravenously every 3 weeks.	Drug: combined therapy using gemcitabine and cisplatin chemotherapy, Lenvatinib and Adebrelimab; Gemcitabine (1000mg/m²) and cisplatin (25mg/m²) on day1 and 8 every 3 weeks, with a total of 6 cycles. Lenvatinib 8 mg once daily (QD) oral dosing, continuous use for 2 years. Adebrelimab 1200mg intravenously every 3 weeks, continuous use for 2 years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	ORR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) at the time of data cutoff as assessed by RECIST 1.1	From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The median overall survival time (mOS)	OS is measured from the start date of the Treatment Phase (date of first study dose) until date of death from any cause. Participants who are lost to follow-up and the participants who are alive at the date of data cutoff will be censored at the date the participant was last known alive or the cut-off date, whichever comes earlier.	From the start date of the Treatment Phase until date of death from any cause (up to approximately 3 years)
The disease control rate (DCR)	DCR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) or stable disease (SD) at the time of data cutoff as assessed by RECIST 1.1	From date of first dose of study drug until disease progression, stable disease, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to approximately 3 years)
The median progression free survival time (mPFS)	The progression free survival time (mPFS) defined as the time from the first study dose date to the date of first documentation of disease progression as assessed by RECIST 1.1	From date of first dose of study drug to the date of first documentation of disease progression (up to approximately 3 years)
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	Safety will be evaluated according to the NCI CTCAE Version 5.0. All observations pertinent to the safety of the study medication will be recorded on the CRF and included in the final report.	From the start date of the Treatment Phase until date of death from any cause (up to approximately 3 years)
Duration of response (DOR)	DOR is defined as the time from the first documentation of CR or PR to the date of first documentation of disease progression or death (whichever occurs first) as assessed by RECIST 1.1	From the first documentation of CR or PR to the first date of documentation of disease progression or death whichever occurs first (up to approximately 3 years)

Collaborators and Investigators

• Sponsor: Nanfang Hospital, Southern Medical University
• Investigators: Principal Investigator: Jinzhang Chen, MD, Nanfang Hospital, Southern Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): February 25, 2024
• Primary Completion (Estimated): February 25, 2025
• Study Completion (Estimated): February 25, 2027

Study Registration Dates

• First Submitted: March 1, 2024
• First Submitted That Met QC Criteria: March 1, 2024
• First Posted (Actual): March 7, 2024

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: cisplatin; Lenvatinib; gemcitabine; Adebrelimab
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Protein Kinase Inhibitors; Lenvatinib; Gemcitabine
• Other Study ID Numbers: NFEC-2024-074

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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