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CholangiocarcinomaPhase 2NCT05348811

HAIC Combined With Donafenib and Sintilimab for Unresectable ICC

A Phase 2 study testing HAIC combined with donafenib and sintilimab in people with Cholangiocarcinoma, run by Zhongda Hospital at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

To evaluate the safety and tolerability of HAIC combined with donafenib and sintilimab in first-line treatment of unresectable ICC. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Cholangiocarcinoma
What is being tested?
HAIC combined with donafenib and sintilimab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteChina
Study dates
13 Jun 2022to 1 Oct 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Unresectable or metastatic histologically or cytologically confirmed ICC
  • No previous systemic treatment or local anti-tumor treatment other than surgery (biliary drainage is allowed), admission was allowed for more than 6 months after the end of adjuvant therapy
  • Child-Pugh score ≤7
  • Life expectancy ≥ 3 months
  • At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST)1.1 criteria
  • Eastern Cooperative Oncology Group(ECOG) performance status (PS) ≤ 1
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  • The functional indicators of important organs meet the following requirements:
  • Adequate blood count, liver-enzymes, and renal function: absolute neutrophil count ≥ 1.5*10^9 /L; platelet (PLT) ≥ 80 *10^9 /L; hemoglobin (HGB) ≥ 9.0 g/dL
  • Bilirubin ≤ 1.5 times upper limits of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 times ULN
  • Serum creatinine ≤ 1.5 times ULN, and creatinine clearance ≥ 60 ml/min (calculated by Cockcroft-Gault formula)
  • International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 times ULN
  • Normal thyroid function, defined as thyroid stimulating hormone (TSH) within the normal range. If the baseline of TSH is outside the normal range, patients with normal total T3 (or FT3) and free tetraiodothyronine (FT4) can also be enrolled
  • The myocardial enzyme profile was within the normal range
  • For women who are not breastfeeding or pregnant, use contraception during treatment or 4 months after the end of treatment
  • Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of the trial
  • Patients who have signed Informed Consent Form (ICF) and are able to perform follow-up visits and the required procedures

Who cannot join

  • Other malignancies diagnosed within 5 years before the first dose, excluding radically cured basal cell carcinoma of skin, squamous cell carcinoma of skin, and/or radically cured carcinoma in situ.
  • Pathological diagnosis of hepatocellular carcinoma (HCC), mixed cholangiocarcinoma and HCC, and other malignant components of non-cholangiocarcinoma
  • Receipt of treatment in other clinical trials within 4 weeks before the first dose
  • Previous receipt of any antibody treatment involving anti-PD-1, anti-PD-L1/L2, or anti-CTLA4 or other immunotherapies
  • Previous receipt of targeted drug(s)
  • Previous receipt of palliative radiotherapy for biliary tract tumors, except for postoperative adjuvant radiotherapy
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  • Previous receipt of Chinese medicines with anti-tumor indications or immunomodulatory drugs (including thymosin, interferon and interleukin, except for local use to control pleural effusion) within 2 weeks before the first dose
  • An active autoimmune disease requiring systemic therapy (e.g., palliative drugs, glucocorticoids, or immunosuppressants) developed within 2 years prior to first administration
  • Have received systemic glucocorticoid therapy (excluding nasal spray, inhalation, or other topical glucocorticoid) or any other form of immunosuppressive therapy during the 4 weeks prior to the study
  • Obstructive jaundice (active treatment, such as biliary drainage or stent, can be included after liver function recovery)
  • Allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation is known
  • Known allergic patients to sintilimab, the active ingredient of donafinib or excipients of the drug under study
  • Not fully recovered from toxicity and/or complications associated with any intervention prior to initiation of treatment (i.e., ≤ grade 1 or baseline, excluding fatigue or hair loss)
  • Human immunodeficiency virus (HIV), HIV 1/2 antibody positive
  • Untreated active hepatitis B (defined as HBsAg positive with hepatitis B virus DNA (HBV-DNA) copy number greater than the ULN in the laboratory department of the research center) [Note: Hepatitis B patients who meet the following criteria can also be enrolled: 1) HBV DNA <2.5*10^3 copies/ml (500 IU/ml) before the first dose, should receive anti-HBV treatment throughout the study period; patients with anti-hepatitis B core antigen(HBc) (+), HBsAg (-), anti-HBs (-) and HBV viral load (-), prophylactic anti-HBV therapy is not required, but viral reactivation needs to be closely monitored]
  • Active HCV-infected subjects (HCV antibody positive and HCV-RNA level above the detection limit)
  • Live attenuated vaccine was administered within 4 weeks prior to initial administration
  • Female subjects who are pregnant, breast-feeding or male/female patients of reproductive potential who are not employing an effective method of birth control (failure rate of less than 1% per year)
  • Presence of any serious or uncontrolled systemic disease, including but not limited to:
  • Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
  • Unstable angina pectoris, congestive heart failure, chronic heart failure with New York Heart Association (NYHA) classification ≥ grade 2
  • Any arterial/venous thromboembolic events within 6 months, including myocardial infarction, unstable angina, cerebrovascular accident or transient cerebral ischemic attack, pulmonary embolism, deep vein thrombosis, or any other history of serious thromboembolism
  • Receipt of major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks before the first dose or having unhealed wounds, ulcers, or fractures. Receipt of tissue biopsy or other minor surgeries within 7 days before the first dose, barring venipuncture and catheterization for intravenous infusion
  • Uncontrolled hypertension (systolic greater than 140 mmHg or diastolic greater than 90 mmHg) after optimal medical treatment, with the history of hypertensive crisis or hypertensive encephalopathy
  • Active tuberculosis
  • Active or poorly clinically controlled serious infections
  • Clinically active diverticulitis, abdominal abscess, gastrointestinal obstruction, gastrointestinal perforation, abdominal fistula within the past 6 months
  • Liver disease such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis
  • Poor control of diabetes (fasting blood glucose > 10 mmol/L)
  • Urine protein ≥ ++, and 24-hour urine protein quantification >1.0 g
  • With mental disorders and unable to cooperate with the treatment
  • Unsuitable for enrollment judged by the investigator

Trial locations and contacts

1 site in 1 country.

China1 site

  • Zhongda Hospital, Southeast University

    Nanjing, Jiangsu, 210009

Other trials in China

About this study

Official title: Hepatic Arterial Infusion Chemotherapy (HAIC) Combined With Donafenib and Sintilimab in First-line Treatment of Unresectable Intrahepatic Cholangiocarcinoma (ICC): a Prospective, Open-label, Phase II Study

To evaluate the safety and tolerability of HAIC combined with donafenib and sintilimab in first-line treatment of unresectable ICC.

Read the detailed description

Compared with systemic intravenous chemotherapy, hepatic arterial infusion chemotherapy(HAIC) has the advantages of improving local drug concentration and reducing toxic and side effects. Currently, it is gradually used in the treatment of intrahepatic cholangiocarcinoma (ICC) with good safety and high objective response rate. Immunotherapy combined with targeted and chemotherapy was well tolerated. At present, anti-programmed cell death protein-1(PD-1) antibody combined with chemotherapy and targeted therapy for advanced biliary tract tumors has initially shown good safety and encouraging efficacy, which is worthy of further exploration. Therefore, this study aims to evaluate the efficacy and safety of HAIC (GEMOX regimen) combined with donafenib and sintilimab in unresectable ICC.

Being tested
HAIC combined with donafenib and sintilimab
Keywords
Hepatic arterial infusion chemotherapy, Donafenib, Sintilimab, Intrahepatic cholangiocarcinoma
Medical subject headings
Cholangiocarcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HAIC combined with donafenib and sintilimabDrug

    Also called HAIC-donafenib-sintilimab

    HAIC- GEMOX regimen, gemcitabine 1000 mg/m2, oxaliplatin 85mg/m2 (if the maximum tumor diameter > 10cm, the dose is 130mg/m2), the first day of each cycle (D1), Q3W. The maximum of 6 times.

    Sintilimab will be given on the first day of each cycle (D1). 200 mg i.v. every 3 weeks until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.The longest treatment time is 24 months.

    Donafenib was taken orally at 0.2 bid on an empty stomach (1 hour before or > 2 hours after meal) in the morning and evening of each administration day, with an interval of about 12 hours. Donafenib treatment is initiated within 1 to 3 days of each HAIC treatment until toxicity is intolerable, the investigator determines disease progression, death, informed consent is withdrawn, new antitumor therapy is initiated, or treatment is discontinued for any other reason specified in the protocol.

Study groups in NCT05348811
Study groupRoleWhat they receive
HAIC combined with donafenib and sintilimabExperimentalHAIC- GEMOX regimen, Day 1, every 3 weeks (Q3W). The maximum of 6 times. Sintilimab will be given on Day 1, 200 mg i.v. Q3W.The longest treatment time is 24 months. Donafenib was taken orally at 0.2 bid on an empty stomach, with an interval of about 12 hours. Donafenib treatment is initiated within 1 to 3 days of each HAIC treatment.
Receives: Drug: HAIC combined with donafenib and sintilimab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective response rate (ORR)

    According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for unresectable intrahepatic cholangiocarcinoma

    Measured: max 24 months

Secondary outcomes (5)

  1. Disease control rate (DCR)

    The time from initiation of either regimen of combination therapy to all-cause death.

    Measured: max 24 months

  2. Duration of response (DOR)

    max 24 months

    Measured: max 24 months

  3. Progression-free survival (PFS)

    Time from initiation therapy to tumor progression according to the modified RECIST criteria or death from any cause.

    Measured: max 24 months

  4. Overall survival (OS)

    The time from initiation of either regimen of combination therapy to all-cause death.

    Measured: max 42 months

  5. Adverse events

    Adverse event (AE)、treatment emergent adverse event (TEAE)、serious adverse event (SAE).

    Measured: max 42 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Apr 2022
  2. Study start13 Jun 2022
  3. Primary completion1 Oct 2025
  4. Study completion1 Oct 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
HAIC (GEMOX regimen) combined with donafenib and sintilimab
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05348811
Sponsor's protocol ID
CHANCE 2203
Status last verified
Jun 2022
First submitted
20 Apr 2022
Last updated
6 Jan 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Blair AB, Alobuia WM, Palta M, Raman SS, Levine MH, Benson AB 3rd, D'Angelica MI, Cloyd JM. Locoregional Treatment Options for Locally Advanced Intrahepatic Cholangiocarcinoma. J Natl Compr Canc Netw. 2025 Aug 14;23(9):e257085. doi: 10.6004/jnccn.2025.7085.

    PubMed 40812353

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing HAIC combined with donafenib and sintilimab in people with Cholangiocarcinoma, run by Zhongda Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (ORR) (time frame: max 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05348811, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2026.

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