Actively Recruiting

Phase 2
Age: 18Years +
All Genders
ID07070700

Cryoablation Combined With Lenvatinib Plus QL1706 (Iparomlimab/Tuvonralimab) in Patients With Advanced Intrahepatic Cholangiocarcinoma (CASTLE-ZS-02): A Single-arm, Multi-cohort Phase 2 Trial

Led by Fudan University · Updated on 2025-08-12

56

Participants Needed

1

Research Sites

N/A

Total Duration

On this page

AI-Summary

What this Trial Is About

Researchers are evaluating the safety and effectiveness of combining cryoablation with lenvatinib plus QL1706 (a bispecific antibody targeting PD-1 and CTLA-4) in patients with advanced intrahepatic cholangiocarcinoma (ICC) who have not responded to first-line treatments. The study is a phase 2 trial involving two groups of patients who have progressed after different prior therapies, including GemCis plus PD-1/PD-L1 inhibitors and other targeted treatments. Participants will receive cryoablation using a two-cycle freeze-thaw protocol, with imaging to monitor the treated area. One to three days after cryoablation, they will begin treatment with lenvatinib taken orally daily (dose based on body weight) and QL1706 given intravenously every 21 days. Both groups receive the same combination treatment following their respective prior therapy failures. During the study, participants will undergo regular assessments including CT or MRI scans to measure tumor response, evaluations of side effects, and blood tests to monitor organ function. Researchers will track how well tumors respond, the duration and timing of responses, disease control, progression-free survival, and overall survival for up to 42 months. Safety and treatment-related adverse events will also be closely monitored throughout the study period.

CONDITIONS

Brief Title

Cryoablation Combined With Lenvatinib Plus QL1706 (Iparomlimab/Tuvonralimab) in Patients With Advanced Intrahepatic Cholangiocarcinoma

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Written informed consent obtained.
  • Age 18 years or older at time of study entry.
  • Unresectable or metastatic histologically or cytologically confirmed intrahepatic cholangiocarcinoma.
  • Failed one line of systemic treatment for advanced cholangiocarcinoma due to progression or toxicity: Cohort A progressed after GemCis plus PD1/PD-L1 inhibitor; Cohort B progressed after GemCis plus PD1/PD-L1 inhibitor and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors.
  • At least one measurable disease site per RECIST criteria via CT scan or MRI.
  • Performance status 2 or less on ECOG scale.
  • Life expectancy of at least 12 weeks.
  • Adequate blood count, liver enzyme, and kidney function within specified limits.
  • Negative pregnancy test for females with reproductive potential within 7 days before trial start.
  • Willing and able to comply with study protocol, including treatment, contraceptive measures, visits, and follow-up.
Not Eligible

You will not qualify if you...

  • History of cardiac disease or significant gastrointestinal bleeding within 4 weeks before treatment.
  • Thrombotic or embolic events within 6 months prior to first study drug dose, except segmental portal vein thrombosis.
  • Prior treatment with cryoablation.
  • Radiofrequency ablation or resection less than 4 weeks before study start.
  • Radiotherapy less than 4 weeks before study start.
  • Major surgery within 4 weeks before study start or not recovered from surgery effects.
  • Second primary cancer except treated basal skin cancer or carcinoma in-situ of the cervix.
  • Immunocompromised status, including HIV positive.
  • Participation in another investigational study within 30 days or 7 half-lives of previous trial medication.
  • Conditions interfering with study treatment or safety evaluation including interstitial lung disease, HBV/HCV coinfection, acute or chronic pancreatitis, active infections, organ transplant, immunodeficiency, recent systemic immunosuppressive therapy, active autoimmune disease requiring systemic treatment, recent live vaccine, CNS metastases unless meeting specific criteria.
  • Medications interfering with study agents.
  • Any other effective cancer treatment except study treatment at start.
  • Prior investigational product within 28 days before entry.
  • Prior therapy with anti-CD137 or anti-CTLA-4 antibodies.
  • Pregnant or breastfeeding females and patients not using effective birth control.
  • History of significant non-compliance or inability to provide reliable informed consent.

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Cryoablation

Duration - 1 day

Participants undergo cryoablation with a two-cycle freeze-thaw phase protocol; imaging is used to visualize the ablation zone.

1 visit (in-person)

Treatment

Duration - Until disease progression or discontinuation

Participants receive lenvatinib orally daily and QL1706 by IV on day 1 of each 21-day cycle until disease progression, unacceptable toxicity, participant request, or withdrawal of consent.

IV treatment every 21 days and daily oral medication

Trial Site Locations

Total: 1 location

1

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, China, 200032

Actively Recruiting

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Research Team

P

Peng Wang, MD

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NON_RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

2

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