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Cholangiocarcinoma, IntrahepaticPhase 2NCT04634058

PD-L1 Antibody Combined With CTLA-4 Antibody for Patients With Advanced Intrahepatic Cholangiocarcinoma Who Progressed After Standard Treatment

A Phase 2 study testing PD-L1 antibody combined with CTLA-4 antibody in people with Cholangiocarcinoma, Intrahepatic and PD-L1, run by Shanghai Zhongshan Hospital at 1 site in China.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The study aims to evaluate the efficacy and safety of PD-L1 antibody combined with the CTLA-4 antibody in patients with advanced ICC who progressed after standard treatment. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cholangiocarcinoma, Intrahepatic, PD-L1, CTLA4
What is being tested?
PD-L1 antibody combined with CTLA-4 antibody
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteChina
Study dates
26 Mar 2021to 30 Sep 2025
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • For unresectable or metastatic or postoperative recurrence, histologically confirmed advanced ICC, provide enough tissue samples for PD-L1, CTLA-4 immunohistochemistry, and exome sequencing
  • The standard systemic treatment of advanced ICC (gemcitabine or platinum or fluorouracil) failed due to disease progression or toxicity
  • There are measurable lesions defined by RECIST standard v1.1
  • For patients with a history of liver chemoembolization, radiofrequency ablation/intervention, or radiotherapy, there must be measurable lesions outside the chemoembolization or radiotherapy area or measurable progression lesions at the chemoembolization or radiotherapy site
  • ECOG physical strength status ≤ 1
  • Life expectancy> 3 months
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  • Adequate renal function: creatinine (Cr) ≤ 1.5 × upper limit of normal (ULN) or glomerular filtration rate (GFR) ≥ 60mL/min/1.73 m2
  • Sufficient liver function: bilirubin ≤ 1.5 × ULN and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 × ULN
  • Sufficient bone marrow reserve: absolute value of neutrophils (ANC)> 1500/mcl, platelets (Plts)> 75,000/mcl, hemoglobin (Hgb) ≥ 9.0g/dl
  • Prothrombin time/activated partial thromboplastin time (PT/PTT) <1.5 × ULN
  • Age ≥18 years old
  • HBV infected persons must meet the following criteria to be eligible to participate in the study:
  • Chronic hepatitis B virus (HBV) infection (defined as hepatitis B surface antigen [HBsAg] positive and/or detectable HBV DNA) subjects must have HBV viral load below 2000 IU/ml before the first dose of the study intervention. Active HBV-treated subjects with a viral load of less than 2000 IU/ml should receive antiviral therapy throughout the study intervention period and check the HBV viral load every 6 weeks. Subjects whose HBV infection is clinically cured (defined as HBsAg negative and anti-HBc positive) and whose HBV viral load cannot be detected during screening should be checked for HBV viral load every 6 weeks. If the viral load exceeds 2000 IU/ml, HBV treatment should be carried out. Antiviral treatment after completing the research intervention should follow local guidelines.
  • The toxicity of the previous treatment has been restored to ≤1 grade (if there is surgery, the wound has completely healed)
  • Female subjects of childbearing age must undergo a pregnancy test within 2 weeks before starting the study medication, and the result is negative, and are willing to use a medically approved high-efficiency contraceptive method during the study period and within 24 weeks after the last study drug administration (Such as intrauterine device, contraceptive pills or condoms); for male subjects whose partners are females of childbearing age, they should agree to use effective methods of contraception during the study period and within 24 weeks after the last study administration
  • Subjects voluntarily joined the study, signed an informed consent form, had good compliance, and cooperated with follow-up.

Who cannot join

  • Past treatment with CTLA-4 mAb
  • Hilar cholangiocarcinoma or extrahepatic cholangiocarcinoma or periampullary carcinoma or gallbladder cancer
  • Major surgery or radiotherapy within 4 weeks before enrollment
  • Active, known, or suspected autoimmune diseases
  • Congestive heart failure or symptomatic coronary artery disease within 3 months before enrollment
  • Cerebrovascular accident occurred in the past 6 months
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  • Clinically significant bleeding, bleeding event, or thromboembolic disease occurred within 6 months
  • History of bowel perforation
  • A history of (non-infectious) pneumonia requiring steroid treatment or current pneumonia
  • Known history of human immunodeficiency virus (HIV) infection
  • History of severely impaired lung function or interstitial lung disease
  • Diagnosed concurrent malignant tumors in the past 5 years (except for fully treated non-melanoma skin cancer, superficial transitional cell carcinoma of the bladder and cervical carcinoma in situ [CIS]) or any currently active malignant tumors
  • HCV RNA positive test indicates the active period
  • Patients who have previously received allogeneic bone marrow transplantation or solid organ transplantation
  • Uncontrollable or symptomatic hypercalcemia
  • Known uncontrollable or symptomatic active central nervous system (CNS) metastasis
  • Symptomatic advanced patients who are at risk of life-threatening complications in the short term (including patients with uncontrollable large amounts of exudate [thoracic cavity, pericardium, abdominal cavity])
  • Known allergies to study drugs or excipients or known severe allergic reactions to any monoclonal antibody
  • Severe infections during screening, including but not limited to infectious complications requiring hospitalization, bacteremia, severe pneumonia, etc.
  • Have received any other experimental drug treatment or participated in another interventional clinical study within 4 weeks before signing the ICF
  • Live attenuated vaccine within 4 weeks before enrollment or planned during the study period and 60 days after the end of study drug treatment
  • Known mental illness, alcohol abuse, inability to quit smoking, drug or drug abuse, etc.
  • Past or current evidence indicates that any conditions, treatments, or laboratory abnormalities that may confuse the research results, interfere with the subject's participation in the entire research process, or the researcher believes that participating in this research is not in the subjects' best interests.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Zhongshan hospital

    Shanghai, 200032

Other trials in China

About this study

Official title: PD-L1 Antibody Combined With CTLA-4 Antibody for Patients With Advanced Intrahepatic Cholangiocarcinoma Who Progressed After Standard Treatment: a Single-arm, Phase II Clinical Study

The study aims to evaluate the efficacy and safety of PD-L1 antibody combined with the CTLA-4 antibody in patients with advanced ICC who progressed after standard treatment.

Read the detailed description

The prognosis of unresectable and metastatic intrahepatic biliary tract cancer (ICC) is extremely poor. The median overall survival of first-line gemcitabine and cisplatin for advanced biliary tumors (including ICC) is only 11.7 months. Currently, there is no standard second-line or third-line treatment for advanced ICC, and there is an urgent need to develop new treatment methods to improve patient survival. Chronic inflammation caused by viral infections and bile duct stones is the most common potential risk factor for ICC. The abnormal immune system plays a key role in the occurrence and development of ICC. The immune checkpoint molecules PD-L1 and CTLA-4 are overexpressed in ICC, and they are obviously heterogeneous, so immunotherapy has potential value. Immune checkpoint inhibitors against PD-1/PD-L1 show a good objective remission rate in advanced biliary tumors (including ICC). CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors show significant clinical enhancement Role, CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors have been clinically studied in a number of solid tumors. In this phase II clinical study, we will evaluate the efficacy and safety of PD-L1 monoclonal antibody combined with CTLA-4 monoclonal antibody in patients with advanced ICC who progressed after standard treatment.

Being tested
PD-L1 antibody combined with CTLA-4 antibody
Medical subject headings
Cholangiocarcinoma

What participants receive

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

  • PD-L1 antibody combined with CTLA-4 antibodyDrug

    After 4 cycles of PD-L1 monoclonal antibody combined with CTLA-4 monoclonal antibody treatment, PD-L1 monotherapy was maintained until the disease progressed or intolerable toxicity and adverse reactions or the medication was used for two years.

Study groups in NCT04634058
Study groupRoleWhat they receive
PD-L1 antibody combined with CTLA-4 antibodyExperimentalAfter 4 cycles of PD-L1 antibody combined with CTLA-4 antibody treatment, PD-L1 monotherapy was maintained until the disease progressed or intolerable toxicity and adverse reactions or the medication was used for two years.
Receives: Drug: PD-L1 antibody combined with CTLA-4 antibody

What is being measured

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

  1. objective response rate (ORR)

    the objective response rate (ORR) of advanced ICC patients who progressed after standard treatment with PD-L1 antibody SHR-1316 combined with CTLA-4 antibody IBI310

    Measured: 12 months

Secondary outcomes (3)

  1. Safety: the potential side effects

    the potiential side effects

    Measured: 12 months

  2. overall survival

    From the beginning date of combined therapy to the date of death

    Measured: 18 months

  3. Progression free survival

    From the beginning date of combined therapy to disease progresion or death, whichever occurs first

    Measured: 12 months

Timeline

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

  1. First posted18 Nov 2020
  2. Study start26 Mar 2021
  3. Primary completion30 Sep 2023
  4. Study completion30 Sep 2025 (estimated)

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
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04634058
Sponsor's protocol ID
zs-ICC-PDCT
Status last verified
Apr 2025
First submitted
17 Nov 2020
Last updated
16 Apr 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Lu JC, Zeng HY, Sun QM, Meng QN, Huang XY, Zhang PF, Yang X, Peng R, Gao C, Wei CY, Shen YH, Cai JB, Dong RZ, Shi YH, Sun HC, Shi YG, Zhou J, Fan J, Ke AW, Yang LX, Shi GM. Distinct PD-L1/PD1 Profiles and Clinical Implications in Intrahepatic Cholangiocarcinoma Patients with Different Risk Factors. Theranostics. 2019 Jul 9;9(16):4678-4687. doi: 10.7150/thno.36276. eCollection 2019.

    PubMed 31367249

  • Lim YJ, Koh J, Kim K, Chie EK, Kim S, Lee KB, Jang JY, Kim SW, Oh DY, Bang YJ. Clinical Implications of Cytotoxic T Lymphocyte Antigen-4 Expression on Tumor Cells and Tumor-Infiltrating Lymphocytes in Extrahepatic Bile Duct Cancer Patients Undergoing Surgery Plus Adjuvant Chemoradiotherapy. Target Oncol. 2017 Apr;12(2):211-218. doi: 10.1007/s11523-016-0474-1.

    PubMed 28084572

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PD-L1 antibody combined with CTLA-4 antibody in people with Cholangiocarcinoma, Intrahepatic and PD-L1, run by Shanghai Zhongshan 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 23 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: under way, not looking for participants, as of the sponsor's last update on 16 Apr 2025. 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?

This study is still under way. Results are not available in the source record yet.

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: 12 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 NCT04634058, which also lists 2 linked publications.

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 16 Apr 2025.

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