Cryoablation with Tislelizumab and Lenvatinib for Advanced Liver Cancer

A Phase II Study of Cryoablation Combined with Tislelizumab Plus Lenvatinib As Second-line or Later Therapy in Patients with Advanced Hepatocellular Carcinoma (CASTLE-02)

This study is testing if combining a freezing treatment with two medications can help people with advanced liver cancer feel better and live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: Tislelizumab, lenvatinib, chemotherapy
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT05057845 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of combining cryoablation with Tislelizumab and lenvatinib as a second-line treatment for patients with advanced hepatocellular carcinoma. The approach leverages cryoablation to destroy tumor tissue, which may enhance the immune response against cancer cells. Tislelizumab, a PD-1 blocking antibody, is used to improve T-cell activity, while lenvatinib is a targeted therapy that has shown promise in treating various cancers. The study aims to determine if this combination can improve patient outcomes compared to existing therapies.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with unresectable or metastatic hepatocellular carcinoma who have failed at least one line of systemic therapy.

Not a fit: Patients with resectable tumors or those who have not yet undergone systemic therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with advanced liver cancer who have not responded to previous therapies.

How similar studies have performed: Other studies have shown promising results with similar combinations of immunotherapy and targeted therapy in various cancers, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* Written informed consent obtained.
* Age ≥ 18 years at time of study entry.
* Participants must have unresectable or metastatic histologically or cytologically confirmed hepatocellular carcinoma
* Participants must have failed 1 line of systemic regimens for advanced hepatocellular carcinoma due to disease progression or toxicity.
* Patients had been refractory or intolerant to previous systemic chemotherapy (oxaliplatin-based chemotherapy), targeted therapy (eg, sorafenib or lenvatinib), or anti-PD-1 or anti-PD-L1 based regimen.
* At least one measurable site of disease as defined by RECIST criteria with spiral CT scan or MRI.
* Performance status (PS) ≤ 2 (ECOG scale).
* 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.

Exclusion Criteria:

* 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.
* RFA and resection administered less then 4 weeks prior to study treatment start.
* Radiotherapy administered less then 4 weeks prior to study treatment start.
* 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:

  1. history of interstitial lung disease
  2. Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) coinfection (i.e double infection)
  3. known acute or chronic pancreatitis
  4. active tuberculosis
  5. any other active infection (viral, fungal or bacterial) requiring systemic therapy
  6. history of allogeneic tissue/solid organ transplant
  7. 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 Tislelizumab treatment.
  8. 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.
  9. Live vaccine within 30 days prior to the first dose of Tislelizumab treatment or during study treatment.
  10. 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.
* Patient has received any other investigational product within 28 days of study entry.
* 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.

Where this trial is running

Shanghai, Shanghai Municipality

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Peng Wang, MD — Fudan University
• Study coordinator: Peng Wang, MD

Conditions Advanced Hepatocellular Carcinoma