HAIC Combined With Tislelizumab and Apatinib for Unresectable Intrahepatic Cholangiocarcinoma

Hepatic Arterial Infusion Chemotherapy Combined With Tislelizumab and Apatinib in the Treatment of Unresectable Intrahepatic Cholangiocarcinoma: A Prospective, Single-Center, Phase II Study

Primary liver cancer is the sixth most common cancer worldwide, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, of which intrahepatic cholangiocarcinoma accounts for 10%-15%. Surgical resection is the only curative method for ICC, but most patients are diagnosed at an advanced stage, and only 15% of patients can undergo surgical resection. In locally advanced ICC patients without distant metastases, although the tumor was initially assessed as unresectable, these patients may have the opportunity for surgical resection after reducing the size tumor lesion and increasing the remnant liver volume through conversion therapy. The current standard first-line treatment for unresectable ICC is gemcitabine combined with cisplatin, with a median overall survival of only 11.7 months and an ORR of 26.1%. In view of the poor effect of the standard chemotherapy regimen, the NCCN guidelines recommend that patients could participate in clinical study. Hepatic arterial infusion chemotherapy can increase the local blood drug concentration and improve the tumor regression rate. By reducing the dose of systemic chemotherapy drugs concentration, the incidence of adverse reactions can be reduced. Hepatic arterial infusion chemotherapy may be a better choice for locally advanced intrahepatic cholangiocarcinoma. PD-1 immunotherapy combined with targeted therapy is expected to improve the prognosis of patients with intrahepatic cholangiocarcinoma. This study investigates the safety and efficacy of hepatic arterial infusion chemotherapy combined with tislelizumab and apatinib in the treatment of unresectable ICC.

Study Overview

• Status: Recruiting
• Conditions: Intrahepatic Cholangiocarcinoma
• Intervention / Treatment: Drug: HAIC Combined with Tislelizumab and Apatinib

• Study Type: Interventional
• Enrollment (Anticipated): 17
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Wei He; Phone Number: +8615521248313; Email: hewei@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • GuangZhou, Guangdong, China, 510060
      • Recruiting
      • Sun yat-sen University Cancer Center
      • Contact: Yunfei Yuan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ICC diagnosed by imaging examination (CT or MRI) and pathology;
• ICC patient without any previous tumor treatment
• The tumor was assessed as unresectable by two liver surgeons. Any of the following conditions: (1) Residual liver volume less than 30-40%; (2) Not possible for R0 radical resection; (3) Tumor invades the portal vein, hepatic artery and bile duct, and the normal residual liver cannot be guaranteed blood supply and bile drainage; the tumor involves the hepatic veins and cannot preserve at least one vein.
• At least one assessable intrahepatic lesion;
• ECOG PS score 0-1;
• Child-Pugh class A;
• Life expectancy is at least 3 months;
• Age between 18 and 75 years old;
• Baseline laboratory tests meet the following criteria:

Neutrophils ≥1.5×10^9/L White blood cells ≥3.0×10^9/L Platelets ≥75×10^9/L Hemoglobin ≥80g/L Serum ALT, AST ≤ 3 x upper limit of normal (ULN) Serum creatinine ≤ 1.5 x ULN INR < 1.5, or prothrombin time < ULN+4 seconds Albumin ≥30g/L Total bilirubin ≤ 3 x upper limit of normal (ULN)

Exclusion Criteria:

• Distant metastasis;
• Refused to receive PD-1 inhibitor and apatinib treatment;
• Any of the following conditions within the first 12 months of the study: myocardial infarction, severe/unstable angina, coronary artery bypass grafting, congestive heart failure, cerebrovascular accident (including transient ischemic attack), Pulmonary embolism; ongoing: arrhythmia grade ≥2 according to NCI-CTCAE criteria, QTc prolongation (>450 ms in men, >470 ms in women);
• Renal insufficiency requires peritoneal dialysis or hemodialysis;
• Serious dysfunction of other important organs;
• A second primary malignant tumor was diagnosed in the past;
• Known or new evidence of brain or leptomeningeal lesions;
• Hemophilia or bleeding tendency, who are taking anticoagulation therapy such as coumarin derivatives in therapeutic doses;
• Pregnant or lactating women, all female patients of childbearing potential must undergo a pregnancy test (serum or urine) within 7 days before enrollment, and the result is negative;
• History of previous organ transplantation;
• Known HIV infection;
• Allergy to chemotherapy drugs;
• Patients with other serious acute or chronic physical or psychiatric diseases or abnormal laboratory tests that may increase the risk associated with participating in the study, or may interfere with the interpretation of the study results or the investigators consider unsuitable for enrollment.

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: HAIC Combined with Tislelizumab and Apatinib

Drug: HAIC Combined with Tislelizumab and Apatinib; Hepatic Arterial Infusion Chemotherapy: FOLFOX6 regimen was infused with chemotherapy drugs: oxaliplatin 130 mg/m2 infusion for 2 hours, folinate calcium 400 mg/m2 infusion for 2 hours, 5-fluorouracil 400 mg/m2 arterial infusion for 10 minutes, 5-fluorouracil 1200 mg/m2 infusion for 23 hours. Every 3 weeks, no more than 4 cycles of HAIC treatment. Tislelizumab and Apatinib treatment: start at 0-3 days after the end of hepatic arterial infusion chemotherapy: Tislelizumab 200 mg, ivdrip, Q3W; Apatinib 250 mg, po, QD.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	The objective response rate was calculated according to the RECIST 1.1.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	defined as the time from the start of enrollment to the time of tumor progression (PD) or death or last follow-up on imaging.	12 months
Disease Control Rate	According to the RECIST 1.1 standard, complete remission + partial remission + disease control rate were calculated.	12 months
Conversion rate to resection	Defined as the rate of surgical resection among all enrolled patients.	12 months
Overall Survival time	Defined as the time from enrollment until death from any cause.	12 months

Collaborators and Investigators

• Sponsor: Yunfei Yuan

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2022
• Primary Completion (Anticipated): May 1, 2023
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: March 7, 2022
• First Submitted That Met QC Criteria: March 21, 2022
• First Posted (Actual): March 22, 2022

Study Record Updates

• Last Update Posted (Actual): August 5, 2022
• Last Update Submitted That Met QC Criteria: August 4, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Apatinib; Tislelizumab; Hepatic Arterial Infusion Chemotherapy; Intrahepatic Cholangiocarcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: B2022-041-01

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