HAIC Plus Targeted Therapy and/or PD-1 Inhibitors for Unresectable Intrahepatic Cholangiocarcinoma

Hepatic Arterial Infusion Chemotherapy Plus Targeted Therapy and/or PD-1 Inhibitors as Conversion Treatment for Unresectable Intrahepatic Cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is associated with poor prognosis. This study aims to explore the efficacy and safety FOLFOX-HAIC in combination with targeted therapy and/or PD-1 inhibitors for patients with initially unresectable ICC, as well as its role in conversion therapy. Data were retrospectively reviewed for patients with locally advanced unresectable ICC treated with FOLFOX-HAIC combined with targeted therapy and/or PD-1 inhibitors. The treatment efficacy and safety were evaluated.

Study Overview

• Status: Completed
• Conditions: Intrahepatic Cholangiocarcinoma
• Intervention / Treatment: Procedure: hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, fluorouracil, and leucovorin (FOLFOX)

• Study Type: Observational
• Enrollment (Actual): 43

Contacts and Locations

Study Locations

• China
  • Guangdong
    • GuangZhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

We reviewed data of patients diagnosed as ICC according to pathology or typical imaging presentation with elevated CA-199 between September 2017 and October 2021 at Sun Yat-Sen University Cancer Center. Patients with ICC confined to the liver and/or regional lymph nodes and treated by FOLFOX-HAIC combined with targeted therapy and anti-PD-1 therapy were evaluated.

Description

Inclusion Criteria:

1. Patients were initially diagnosed without any previous oncological treatment.
2. The tumor was assessed as unresectable by two hepatobiliary surgeons (BL and YY, with more than 15 years of experience). 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.
3. At least one assessable intrahepatic lesion.
4. classified as Child-Pugh Grade A.
5. ECOG PS score 0-1.
6. baseline blood tests meet the following criteria: leukocytes ≥3.0×10^9/L; neutrophils ≥1.5×10^9/L; platelets ≥75×10^9/L; hemoglobin ≥ 80g/L; serum ALT or AST ≤ 3 times of upper limit of normal (ULN); serum creatinine ≤1.5 x ULN; INR ≤ 1.5, or prothrombin time ≤ ULN + 4 seconds; albumin ≥ 30 g/L; total bilirubin ≤ 3 x ULN.

Exclusion Criteria:

1. severe underlying cardiac, pulmonary, or renal diseases.
2. a second primary malignancy.
3. prior history of organ transplantation.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

FOLFOX-HAIC plus targeted therapy and/or PD-1 inhibitors; FOLFOX-HAIC as the following dosage: 130 mg/m2 oxaliplatin infusion for 2 hours; 400 mg/m2 of leucovorin infusion for 2 hours; and 400 mg/ m2 of 5-FU bolus and 1200 of mg/m2 continuous infusion of 5-FU for 23 hours. Patients received targeted therapy, three different targeted therapy were applied including: 1. lenvatinib 2. sorafenib; 3. apatinib. A portion of patients received PD-1 inhibitor administered intravenously every three weeks.

Procedure: hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, fluorouracil, and leucovorin (FOLFOX); FOLFOX-HAIC as the following dosage: 130 mg/m2 oxaliplatin infusion for 2 hours; 400 mg/m2 of leucovorin infusion for 2 hours; and 400 mg/ m2 of 5-FU bolus and 1200 of mg/m2 continuous infusion of 5-FU for 23 hours. Patients received targeted therapy, three different targeted therapy were applied including: 1. lenvatinib 2. sorafenib; 3. apatinib. A portion of patients received PD-1 inhibitor administered intravenously every three weeks.; Other Names: PD-1 inhibitors; targeted therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Response	The tumor responses were evaluated by measuring the longest diameter of target lesions according to response evaluation criteria in solid tumors (RECIST) version 1.1	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival (OS) was measured from the initiation of transarterial therapy to the date of death or the last follow-up.	24 months
Progression-free survival	Progression-free survival (PFS) was measured from the initiation of transarterial therapy to the time of progression or recurrence or last follow-up.	24 months
Conversion rate	Rate of patients underwent hepatic surgery after careful evaluation when an estimated residual liver volume >30-40% could be remained after R0 surgery by 2 experienced surgeons.	24 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2017
• Primary Completion (Actual): August 31, 2021
• Study Completion (Actual): January 31, 2022

Study Registration Dates

• First Submitted: August 4, 2022
• First Submitted That Met QC Criteria: August 4, 2022
• First Posted (Actual): August 5, 2022

Study Record Updates

• Last Update Posted (Actual): August 10, 2022
• Last Update Submitted That Met QC Criteria: August 7, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Targeted Therapy; Hepatic Arterial Infusion Chemotherapy; PD-1 Inhibitors
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Immune Checkpoint Inhibitors
• Other Study ID Numbers: B2022-222-01

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