HAIC Plus Systemic Therapy as De-escalation Therapy Strategy for Biliary Tract Cancer

May 5, 2026 updated by: Peking University

HAIC Combined With Systemic Therapy as De-escalation Therapy Strategy for Biliary Tract Cancer: A Conceptual Study

Biliary tract cancer (BTC), including cholangiocarcinoma and gallbladder cancer (GBC), is a group of malignancies with highly heterogeneous, highly aggressiveness, and poor prognosis. Surgery is recognized as the only curative treatment for BTC, however, only about 20% BTC patients are eligible for curative resection since most patients with BTC are diagnosed at an advanced stage. The median overall survival (OS) in patients with unresectable BTC is typically less than 6 months. For patients with unresectable BTC, gemcitabine plus cisplatin (GemCis) had been recommended as the standard first-line treatment for many years. However, the objective response rate (ORR) of this regimen is only 26.1%, and the survival benefit remains limited, with a median OS of less than one year.

In recent years, two phase III trials (TOPAZ-1 and KEYNOTE-966) have demonstrated that combining immune checkpoint inhibitors (durvalumab or pembrolizumab) with the GemCis regimen could further prolong survival in patients with BTC, achieving a median OS of 12.9 months and 12.7 months, respectively. Based on this evidence, many guidelines worldwide had recommended GemCis plus durvalumab or pembrolizumab as the preferred standard first-line treatment for patients with unresectable BTC. However, survival benefits from this combination therapy remain relatively limited, and tumor response is suboptimal, with an ORR of only 26.7%-29%.

Hepatic arterial infusion chemotherapy (HAIC) enables continuous infusion of chemotherapeutic agents via the hepatic artery, significantly increasing local drug concentration at the tumor site, maximizing antitumor efficacy, and achieving a higher ORR (50%-60%) with substantial reduction in tumor burden. In recent years, HAIC has been increasingly used in the treatment of unresectable BTC, with its efficacy supported by many clinical studies.

Firstly, HAIC provides survival benefits comparable to surgery in patients with multifocal intrahepatic cholangiocarcinoma (iCCA), and significantly outperforms systemic therapy. In 2022, a retrospective study enrolled 141 patients who received HAIC and 178 patients who underwent surgical resection from 12 centers. The results showed the median OS was 20.3 months in the HAIC group and 18.9 months in the resection group (P = 0.32), indicating comparable survival outcomes between HAIC and surgery. Given the risks of post-hepatectomy complications, HAIC may serve as an effective alternative treatment strategy for multifocal iCCA. Furthermore, for locally advanced unresectable iCCA, the results in a study in 2024 comparing HAIC with GemCis regimen chemotherapy revealed that although patients in the HAIC group had a higher tumor burden (proportion of multifocal disease: 73.4% vs. 55.3%, P = 0.023), the median OS in HAIC group remained significantly superior to that in the GemCis group (27.7 months vs. 11.8 months, P < 0.001).

Secondly, HAIC has also been demonstrated to be effective in treating perihilar cholangiocarcinoma (pCCA). In 2017, a single-arm, prospective phase II trial conducted in our center showed HAIC with oxaliplatin and fluorouracil yielded an ORR of 67.6%, a median progression-free survival (PFS) of 12.2 months, and a median OS of 20.5 months in treating perihilar cholangiocarcinoma (pCCA).

Furthermore, HAIC also has clinical potential in treating advanced GBC. In 2021, a retrospectively study in our center enrolled 26 patients with advanced GBC who received HAIC with oxaliplatin and fluorouracil, of whom 23.1% had failed prior systemic therapy and 34.6% had contraindications to systemic treatment. The results showed that HAIC achieved a median PFS of 10 months and a median OS of 13.5 months, with an ORR of 69.2% and a disease control rate (DCR) of 92.3%.

In recent years, many studies have demonstrated that HAIC combined with systemic therapy could yield significant survival benefits in patients with unresectable BTC. A phase II clinical trial in 2022 evaluated the efficacy of HAIC with floxuridine plus systemic gemcitabine and oxaliplatin (GEMOX) in unresectable iCCA. The results showed that the combination therapy achieved a median PFS of 11.8 months and a median OS of 25 months, with a 6-month DCR of 84%, and 58% of patients achieved partial response (PR). Additionally, the association of benefit of combining HAIC with systemic chemotherapy and stage of BTC has been reported, and that patients with locally advanced cholangiocarcinoma may not derive such benefit from this combination. In 2025, a phase II clinical trial conducted in our center evaluated the efficacy and safety of HAIC (bevacizumab, oxaliplatin, and fluorouracil) combined with toripalimab as a first-line treatment for unresectable BTC. The results showed a median PFS of 13.2 months and a median OS of 19 months, with an ORR as high as 84.38%. Some patients achieved successful conversion resection following this combination therapy, and postoperative pathology confirmed pathological complete res

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Beijing, China
        • Not yet recruiting
        • Peking University Cancer Hospital
        • Contact:
      • Beijing, China, 100142
        • Recruiting
        • Peking University Cancer Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Study Population

Patients with advanced BTC and treated by HAIC combined with systemic therapy from single center in China.

Description

Inclusion Criteria:

  • Age: 18-80 years, both genders.
  • Diagnosis of biliary tract cancer (including intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, and gallbladder cancer) and confirmed by histopathological or cytopathological examination.
  • Without distant metastasis or limited distant metastasis
  • Treatment-naive.
  • ECOG PS score < 2.
  • Child-Pugh score: Class A or B (≤7).
  • Normal major organ function, meeting the following standards:(1) Blood routine examination:A. Hb≥90 g/L;B. ANC≥1.5×10^9/L;C. PLT≥75×10^9/L;(2) Biochemical examination:A. ALB ≥30g/L;B. ALT and AST<5×ULN;C. TBiL ≤5×ULN;D. Creatinine ≤1.5×ULN;(3) Coagulation function:A. International normalized ratio (INR) ≤1.5×ULN;B. Activated partial thromboplastin time (APTT) ≤1.5×ULN.

Exclusion Criteria:

  • Coexistent or synchronous malignancies.
  • Distal cholangiocarcinoma.
  • Allergic to contrast agents or oxaliplatin.
  • Pregnant or lactating women.
  • Multiple extrahepatic metastases or combined malignant pleural and peritoneal effusions.
  • History of organ transplantation.
  • With infections requiring anti-infection treatment.
  • Severe and irreparable coagulation dysfunction.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Locally advanced group
Patients with BTC at locally advanced stage
Procedure: HAIC(GOLF)
Hepatic arterial chemotherapy consisted of infusions of gemcitabin (1000 mg/m2 for 2 hours, d1), oxaliplatin (35 mg/m2 for 2 hours, d1-2), followed by 5-fluorouracil (750 mg/m2 for 22 hours, d1-2) every 3-4 weeks.
Drug: Bevacizumab
7.5 mg/kg intravenously before HAIC every 3-4 weeks
Drug: PD-1/PD-L1 inhibitor
PD-1/PD-L1 inhibitor injection intravenously or percutaneously every 3-4 week
Procedure: De-escalation strategy
curative treatment (surgery, ablation, SIRT, or SBRT) or maintenance treatment (S-1, Bevacizumab, and PD-1/PD-L1 inhibitor) when tumor response got CR, PR, or SD
Procedure: Second-line treatment
Other treatments when tumor response got PD
Experimental: Advanced group
Patients with BTC at advanced stage
Drug: Bevacizumab
7.5 mg/kg intravenously before HAIC every 3-4 weeks
Drug: PD-1/PD-L1 inhibitor
PD-1/PD-L1 inhibitor injection intravenously or percutaneously every 3-4 week
Procedure: De-escalation strategy
curative treatment (surgery, ablation, SIRT, or SBRT) or maintenance treatment (S-1, Bevacizumab, and PD-1/PD-L1 inhibitor) when tumor response got CR, PR, or SD
Procedure: Second-line treatment
Other treatments when tumor response got PD
Procedure: HAIC (FOLFOX)
Hepatic arterial chemotherapy consisted of infusions of oxaliplatin (35 mg/m2 for 2 hours, d1-2), followed by 5-fluorouracil (750 mg/m2 for 22 hours, d1-2) every 3-4 weeks.
Drug: Gemcitabin
1000 mg/m2 intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
OS
Time Frame: From date of treatment beginning until the date of death from any cause, assessed up to 36 months.
The time from treatment initiation to death due to any cause
From date of treatment beginning until the date of death from any cause, assessed up to 36 months.
clinical complete response rate
Time Frame: From date of treatment beginning until the date of first documented progression disease, up to 36 months.
The proportion of participants in the analysis population who have clinical complete response (CR) determined by investigators using mRECIST criteria at any time during the study.
From date of treatment beginning until the date of first documented progression disease, up to 36 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PFS
Time Frame: From date of treatment beginning until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
The time from treatment initiation to the first documented disease progression or death due to any cause, whichever occurs firstly.
From date of treatment beginning until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
ORR
Time Frame: From date of treatment beginning until the date of first documented progression disease, up to 36 months.
The proportion of participants in the analysis population who have complete response (CR) or partial response (PR) determined by investigators using mRECIST criteria at any time during the study.
From date of treatment beginning until the date of first documented progression disease, up to 36 months.
Number of patients with treatment-related adverse events
Time Frame: From date of treatment beginning until the date of study treatment completion, up to 36 months.
Number of patients with AE, treatment-related AE (TRAE), serious adverse event (SAE) assessed by CTCAE v5.0.
From date of treatment beginning until the date of study treatment completion, up to 36 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University

Investigators

  • Study Director: Xiaodong Wang, Peking University Cancer Hospital & Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 31, 2026

Primary Completion (Estimated)

March 31, 2028

Study Completion (Estimated)

March 31, 2029

Study Registration Dates

First Submitted

February 19, 2026

First Submitted That Met QC Criteria

March 11, 2026

First Posted (Actual)

March 12, 2026

Study Record Updates

Last Update Posted (Actual)

May 8, 2026

Last Update Submitted That Met QC Criteria

May 5, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HOST

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Biliary Tract Cancer (BTC)

Clinical Trials on HAIC(GOLF)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Cambodia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe