Cryoablation with Tislelizumab and Lenvatinib for liver metastasis from gastric cancer

A Phase II Study to Evaluate the Efficacy and Safety of Cryoablation Combined With Tislelizumab Plus Lenvatinib in Previously Treated Gastric Cancer Liver Metastasis

This study is testing if a combination of freezing treatment and two medications can help people with gastric cancer that has spread to the liver after they’ve already tried other treatments.

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, chemotherapy, Lenvatinib
• Locations: 2 sites (Shanghai, Shanghai and 1 other locations)
• Trial ID: NCT05893056 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of combining cryoablation with Tislelizumab and Lenvatinib in patients with gastric cancer that has spread to the liver, specifically in those who have already undergone previous treatments. The approach leverages cryoablation to destroy tumor tissue, which may enhance the immune response against cancer cells, while Tislelizumab and Lenvatinib work to inhibit tumor growth and promote immune activity. Participants must have measurable disease and have failed at least one prior chemotherapy regimen. The study aims to determine if this combination can improve patient outcomes in a second- or third-line treatment setting.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with gastric cancer liver metastasis who have previously failed at least one systemic chemotherapy regimen.

Not a fit: Patients who have not received prior systemic chemotherapy or those with performance status greater than 2 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 gastric cancer liver metastasis who have limited treatment choices.

How similar studies have performed: Other studies have shown promising results with similar combinations of immunotherapy and targeted therapy, 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 gastric cancer liver metastasis.
* Participants must have failed at least one previous systemic chemotherapy regimens in the liver metastatic setting.
* Participants who had received previous anti-angiogenesis or anti-PD1/PDL1 therapy were 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).
* 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:

* 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.
* 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:

  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.
* 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 and 1 other locations

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

Study contacts

• Study coordinator: Peng Wang, MD

Conditions Gastric Cancer Metastatic to Liver