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Intrahepatic CholangiocarcinomaPhase 2NCT05010668

Cryoablation Combined With Sintilimab Plus Lenvatinib in Patients With Advanced Intrahepatic Cholangiocarcinoma

A Phase 2 study testing cryoablation, Sintilimab and lenvatinib in people with Intrahepatic Cholangiocarcinoma, run by Fudan University 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

The objective of this study is to evaluate the efficacy and safety of cryoablation combined with Sintilimab plus lenvatinib in patients with advanced intrahepatic Cholangiocarcinoma after progression on first line systemic therapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Intrahepatic Cholangiocarcinoma
What is being tested?
cryoablation, Sintilimab and lenvatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
1 siteChina
Study dates
24 Aug 2021to 2 Mar 2024
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent obtained.
  • Age ≥ 18 years at time of study entry.
  • Participants must have unresectable or metastatic histologically or cytologically confirmed intrahepatic cholangiocarcinoma
  • Participants must have failed 1 line of systemic regimens for advanced cholangiocarcinoma due to disease progression or toxicity.
  • At least one measurable site of disease as defined by RECIST criteria with spiral CT scan or MRI.
  • Performance status (PS) ≤ 2 (ECOG scale).
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  • Life expectancy of at least 12 weeks.
  • Adequate blood count, liver-enzymes, and renal function: absolute neutrophil count ≥ 1,500/L, platelets ≥75 x103/L; Total bilirubin ≤ 3x upper normal limit; Aspartate Aminotransferase (SGOT), Alanine aminotransferase (SGPT) ≤ 5 x upper normal limit (ULN); International normalized ratio (INR) ≤1.25; Albumin ≥ 31 g/dL; Serum Creatinine ≤ 1.5 x institutional ULN or creatinine clearance (CrCl) ≥ 30 mL/min (if using the Cockcroft-Gault formula )
  • Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.
  • Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment, adherence to contraceptive measures, scheduled visits and examinations including follow up.

Who cannot join

  • History of cardiac disease, including clinically significant gastrointestinal bleeding within 4 weeks prior to start of study treatment
  • Thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months Prior to the first dose of study drug with the exception of thrombosis of a segmental portal vein.
  • Prior treatment with cryoablation.
  • Prior treatment with Lenvatinib or other targeted therapy.
  • RFA and resection administered less then 4 weeks prior to study treatment start.
  • Radiotherapy administered less then 4 weeks prior to study treatment start.
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  • Major surgery within 4 weeks of starting the study treatment OR subjects who have not recovered from effects of major surgery.
  • Patients with second primary cancer, except adequately treated basal skin cancer or carcinoma in-situ of the cervix.
  • Immunocompromised patients, e.g. patients who are known to be serologically positive for human immunodeficiency virus (HIV).
  • Participation in another clinical study with an investigational product during the last 30 days before inclusion or 7 half-lifes of previously used trial medication, whichever is longer.
  • Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study Treatment or interpretation of patient safety or study results, including but not limited to:
  • history of interstitial lung disease
  • Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) coinfection (i.e double infection)
  • known acute or chronic pancreatitis
  • active tuberculosis
  • any other active infection (viral, fungal or bacterial) requiring systemic therapy
  • history of allogeneic tissue/solid organ transplant
  • diagnosis of immunodeficiency or patient is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of nivolumab-monotherapy treatment.
  • Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Exceptions: Subjects with vitiligo, hypothyroidism, diabetes mellitus type I or resolved childhood asthma/atopy are an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with Hashimoto thyroiditis, hypothyroidism stable on hormone replacement or psoriasis not requiring treatment are not excluded from the study.
  • Live vaccine within 30 days prior to the first dose of nivolumab-monotherapy treatment or during study treatment.
  • History or clinical evidence of Central Nervous System (CNS) metastases Exceptions are: Subjects who have completed local therapy and who meet both of the following criteria: I. are asymptomatic and II. have no requirement for steroids 6 weeks prior to start of nivolumab-monotherapy treatment. Screening with CNS imaging (CT or MRI) is required only if clinically indicated or if the subject has a history of CNS
  • Medication that is known to interfere with any of the agents applied in the trial.
  • Any other efficacious cancer treatment except protocol specified treatment at study start.
  • Patient has received any other investigational product within 28 days of study entry.
  • Prior therapy with an anti-Programmed cell death protein 1 (anti-PD-1), anti-PD-L1, anti-Programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor (TNFR) family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
  • 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). [Acceptable methods of contraception are: implants, injectable contraceptives, combined oral contraceptives, intrauterine pessars (only hormonal devices), sexual abstinence or vasectomy of the partner]. Women of childbearing potential must have a negative pregnancy test (serum β-HCG) at screening.
  • Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Fudan University Shanghai Cancer Center

    Shanghai, 200032

Other trials in China

About this study

Official title: A Phase II Study of Cryoablation Combined With Sintilimab Plus Lenvatinib in Patients With Advanced Intrahepatic Cholangiocarcinoma (CASTLE-01)

The objective of this study is to evaluate the efficacy and safety of cryoablation combined with Sintilimab plus lenvatinib in patients with advanced intrahepatic Cholangiocarcinoma after progression on first line systemic therapy.

Read the detailed description

Recent studies have suggested that local destruction of tumor tissue by cryoablation induced activation and maturation of dendritic cells and tumor-specific T cells by cross-presentation of tumor antigens. While pd-1 blocking antibody interferes with PD-1 mediated T-cell regulatory signaling. And combination of pd-1 blocking antibody plus lenvatinib showed increased ORR in many type of human cancers, including advanced intrahepatic cholangiocarcinoma. Therefore, the objective of this study is to evaluate the efficacy and safety of cryoablation combined with Sintilimab plus lenvatinib in patients with advanced intrahepatic cholangiocarcinoma.

Being tested
cryoablation, Sintilimab, lenvatinib
Medical subject headings
Cholangiocarcinoma

What participants receive

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

  • cryoablationDrug

    Cryoablation treatment starts at day 0.

  • SintilimabDrug

    Sintilimab will be initiated on day 14 after cryoablation. Sintilimab will be administered at 200 mg i.v. every 3 weeks until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.

  • lenvatinibDrug

    Lenvatinib will be initiated on day 14 after cryoablation. Lenvatinib will be administered (bodyweight ≥ 60 kg, 12 mg; < 60 kg, 8 mg) orally daily every 3 weeks until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.

Study groups in NCT05010668
Study groupRoleWhat they receive
Cryoablation in combination with Sintilimab plus lenvatinibExperimentalNot described
Receives: Drug: cryoablation; Drug: Sintilimab; Drug: lenvatinib

What is being measured

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

  1. Objective Response Rate (ORR)

    ORR according to RECIST 1.1

    Measured: max 24 months

Secondary outcomes (5)

  1. DoR

    Duration of Response

    Measured: max 24 months

  2. PFS

    Progression-free survival

    Measured: max 24 months

  3. OS

    overall survival

    Measured: max 42 months

  4. DCR

    disease control rate

    Measured: max 24 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 posted18 Aug 2021
  2. Study start24 Aug 2021
  3. Primary completion2 Mar 2024
  4. Study completion2 Mar 2024

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
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05010668
Sponsor's protocol ID
MIT-014
Status last verified
Dec 2024
First submitted
11 Aug 2021
Last updated
21 Feb 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Gu S, Luo Q, Zhang Y, Qian L, Chen K, Liang F, Hu Y, Zhou R, Wang Y, Liu J, Ning Z, Xu L, Meng Z, Li Y, Wang P. Cryoablation plus sintilimab and lenvatinib in advanced or metastatic intrahepatic cholangiocarcinoma: a phase 2 trial. Nat Cancer. 2026 Jan;7(1):60-79. doi: 10.1038/s43018-025-01058-2. Epub 2025 Nov 1.

    PubMed 41176543

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing cryoablation, Sintilimab and lenvatinib in people with Intrahepatic Cholangiocarcinoma, run by Fudan University 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 10 inclusion and 27 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 21 Feb 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?

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 NCT05010668, 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 21 Feb 2025.

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