Advanced Intrahepatic CholangiocarcinomaPhase 2NCT05835245
Cryoablation Combined With Sintilimab Plus Lenvatinib in 1L Treatment of Advanced ICC (CASTLE-ICC-Chemo-free)
A Phase 2 study testing Cryoablation, Sintilimab and Lenvatinib in people with Advanced Intrahepatic Cholangiocarcinoma, run by Fudan University at 1 site in China.
Trial summary
The objective of this study is to evaluate the efficacy and safety of cryoablation combined with Sintilimab plus lenvatinib as first-line treatment in patients with advanced ICC. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Intrahepatic Cholangiocarcinoma
- What is being tested?
- Cryoablation, Sintilimab and Lenvatinib
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 28 Apr 2023to 30 Dec 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 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.
- Advanced ICC with diagnosis confirmed by histology or cytology.
- Patients with no prior systemic chemotherapy or targeted therapy or loco-regional therapy (including but not limited to transarterial chemoembolization, transarterial embolization, transarterial chemotherapy or transarterial radioembolization) or immunotherapy for ICC. Patients with recurrent disease more than 6 months after completion of adjuvant chemotherapy following curative resection are eligible.
- At least one measurable site of disease as defined by RECIST v1.1 with spiral CT scan or MRI.
- Performance status (PS) ≤ 2 (ECOG scale).
Show all 10Show fewer
- 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
- Diagnosis of hepatocellular carcinoma (HCC), mixed cholangiocarcinoma and HCC, sarcomatoid hepatocellular carcinoma, or hepatic fibrolamellar carcinoma by histology or cytology.
- Uncontrolled pericardial effusion, pleural effusion, or clinically significant moderate or severe ascites that is symptomatic or requires thoracentesis or paracentesis during the screening phase for control of symptoms.
- 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.
- Major surgery within 4 weeks of starting the study treatment OR subjects who have not recovered from effects of major surgery.
Show all 23Show fewer
- 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).
- 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 Sintilimab 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 Sintilimab 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 Tislelizumab 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.
- 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, 1 recruiting
- Recruiting
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 200032
Peng Wang, M.D., 862164175590 ext. 83630, peng_wang@fudan.edu.cn
About this study
Official title: A Phase II Study to Evaluate the Efficacy and Safety of Cryoablation Combined With Sintilimab Plus Lenvatinib as First-line Treatment in Patients With Unresectable Advanced Intrahepatic Cholangiocarcinoma (ICC)
The objective of this study is to evaluate the efficacy and safety of cryoablation combined with Sintilimab plus lenvatinib as first-line treatment in patients with advanced ICC.
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 types of human cancers. Therefore, the objective of this study is to evaluate the efficacy and safety of cryoablation combined with Sintilimab plus lenvatinib as first-line treatment in patients with advanced ICC.
- Conditions
- Advanced Intrahepatic Cholangiocarcinoma
- Being tested
- Cryoablation, Sintilimab, Lenvatinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CryoablationProcedure or surgery
Cryoablation is performed under US or CT guidance per Investigator decision.
SintilimabDrug
a PD-1 immune check inhibitor
LenvatinibDrug
Lenvatinib capsules
| Study group | Role | What they receive |
|---|---|---|
| Cryoablation combined with Sintilimab and Lenvatinib | Experimental | Cryoablation treatment starts at day 0. Sintilimab and Lenvatinib will be initiated on day 1 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. 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. Receives: Procedure: Cryoablation; Drug: Sintilimab; Drug: Lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
ORR is defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by investigator.
Measured: max 24 months
Secondary outcomes (5)
Duration of Response (DOR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
DOR is defined as the time from first documented complete or partial response until disease progression, death from any cause, or censoring at date of last tumor assessment.
Measured: max 24 months
Progression Free Survival (PFS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
PFS is defined as the time from study treatment to disease progression or all-cause death as assessed by the investigator (whichever occurs first)
Measured: max 24 months
Overall survival (OS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
OS is defined as the time from study treatment to the date of death of the subject, regardless of the cause of death
Measured: max 42 months
Disease control rate (DCR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
DCR is defined as the proportion of patients with complete response (CR), partial response (PR) and stable disease (SD)
Measured: max 24 months
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience at least one AE will be reported.
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.
- First posted28 Apr 2023
- Study start28 Apr 2023
- Primary completion30 Dec 2025 (estimated)
- Study completion30 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Intrahepatic CholangiocarcinomaStudies of the same condition, open and under way.
- More trials run by Fudan UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Peng Wang, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05835245
- Sponsor's protocol ID
- 2304273-15
- Status last verified
- May 2023
- First submitted
- 18 Apr 2023
- Last updated
- 31 May 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study to Evaluate the Efficacy and Safety of Cryoablation Combined With Sintilimab Plus Lenvatinib as First-line Treatment in Patients With Unresectable Advanced Intrahepatic Cholangiocarcinoma (ICC)
- ClinicalTrials.gov ID
- NCT05835245
- Acronym / sponsor ID
- 2304273-15
- Conditions
- Advanced Intrahepatic Cholangiocarcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 28 Apr 2023 (actual)
- Primary completion
- 30 Dec 2025 (estimated)
- Study completion
- 30 Dec 2025 (estimated)
- First posted
- 28 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this study is to evaluate the efficacy and safety of cryoablation combined with Sintilimab plus lenvatinib as first-line treatment in patients with advanced ICC.
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 types of human cancers. Therefore, the objective of this study is to evaluate the efficacy and safety of cryoablation combined with Sintilimab plus lenvatinib as first-line treatment in patients with advanced ICC.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cryoablation combined with Sintilimab and Lenvatinib | Experimental | Procedure: Cryoablation, Drug: Sintilimab, Drug: LenvatinibCryoablation treatment starts at day 0. Sintilimab and Lenvatinib will be initiated on day 1 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. 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Written informed consent obtained.
- Age ≥ 18 years at time of study entry.
- Advanced ICC with diagnosis confirmed by histology or cytology.
- Patients with no prior systemic chemotherapy or targeted therapy or loco-regional therapy (including but not limited to transarterial chemoembolization, transarterial embolization, transarterial chemotherapy or transarterial radioembolization) or immunotherapy for ICC. Patients with recurrent disease more than 6 months after completion of adjuvant chemotherapy following curative resection are eligible.
- At least one measurable site of disease as defined by RECIST v1.1 with spiral CT scan or MRI.
Key exclusion criteria (23 listed)
- Diagnosis of hepatocellular carcinoma (HCC), mixed cholangiocarcinoma and HCC, sarcomatoid hepatocellular carcinoma, or hepatic fibrolamellar carcinoma by histology or cytology.
- Uncontrolled pericardial effusion, pleural effusion, or clinically significant moderate or severe ascites that is symptomatic or requires thoracentesis or paracentesis during the screening phase for control of symptoms.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CryoablationCryoablation is performed under US or CT guidance per Investigator decision. | Procedure or surgery | Cryoablation combined with Sintilimab and Lenvatinib |
| Sintilimaba PD-1 immune check inhibitor | Drug | Cryoablation combined with Sintilimab and Lenvatinib |
| LenvatinibLenvatinib capsules | Drug | Cryoablation combined with Sintilimab and Lenvatinib |
Primary outcome
Objective Response Rate (ORR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
Time frame: max 24 months
ORR is defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by investigator.
5 secondary outcomes
Duration of Response (DOR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
Time frame: max 24 months
Progression Free Survival (PFS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
Time frame: max 24 months
Overall survival (OS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
Time frame: max 42 months
Disease control rate (DCR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
Time frame: max 24 months
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time frame: max 42 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2023.
- Individual participant dataSharing planned: No
Related trials for Advanced Intrahepatic Cholangiocarcinoma
RecruitingPhase 3
Efficacy and Safety of Zanidatamab With Standard-of-care Therapy Against Standard-of-care Therapy for Advanced HER2-positive Biliary Tract Cancer
Biliary Tract Cancer
RecruitingPhase 2
Perioperative Retlirafusp Alfa(Anti-PD-L1/TGF-β Bifunctional Fusion Protein) Plus Famitinib and GEMOX-Based Hepatic Arterial Infusion Chemotherapy for Locally Advanced Intrahepatic Cholangiocarcinoma: A Multicenter, Single-Arm, Exploratory Phase II Trial
Intrahepatic Cholangiocarcinoma (Icc), Neoadjuvant Therapy
Active, not recruitingPhase 2
Testing the Combination of Pevonedistat With Chemotherapy for Bile Duct Cancer of the Liver
Metastatic Cholangiocarcinoma, Metastatic Hepatocellular Carcinoma
RecruitingPhase 1/2
A Phase 1/2 Study of VS-7375 in Patients With KRAS G12D-Mutated Solid Tumors
Pancreatic Ductal Adenocarcinoma, Non Small Cell Lung Cancer
Active, not recruitingPhase 2
Study of Chemotherapy, With or Without Binimetinib in Advanced Biliary Tract Cancers in 2nd Line Setting (A ComboMATCH Treatment Trial)
Advanced Biliary Tract Carcinoma, Advanced Gallbladder Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cryoablation, Sintilimab and Lenvatinib in people with Advanced 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 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: status not confirmed, as of the sponsor's last update on 31 May 2023. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Peng Wang, MD (86-21-64175590, wangp413@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (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?
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 31 May 2023.