Cryoablation Combined With Tislelizumab Plus Lenvatinib In Previously Treated Gastric Cancer Liver Metastasis (CASTLE-09)

NCT ID: NCT05893056

Last Updated: 2023-06-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-16
• Study Completion Date: 2025-12-30

Brief Summary

The objective of this study is to evaluate the efficacy and safety of cryoablation combined with Tislelizumab plus Lenvatinib for patients with gastric cancer liver metastasis in the second-/third-Line setting.

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 Tislelizumab plus Lenvatinib in previously treated gastric cancer liver metastasis.

Conditions

Gastric Cancer Metastatic to Liver

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cryoablation combined with Tislelizumab and lenvatinib

Cryoablation treatment starts at day 0. Tislelizumab and Lenvatinib will be initiated on day 14 after cryoablation. Tislelizumab 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.

Group Type: EXPERIMENTAL

Cryoablation

Intervention Type: PROCEDURE

Cryoablation is performed under US or CT guidance per Investigator decision.

Tislelizumab

Intervention Type: DRUG

a PD-1 immune check inhibitor

Lenvatinib

Intervention Type: DRUG

Lenvatinib capsules

Interventions

Cryoablation

Cryoablation is performed under US or CT guidance per Investigator decision.

Intervention Type: PROCEDURE

Tislelizumab

a PD-1 immune check inhibitor

Intervention Type: DRUG

Lenvatinib

Lenvatinib capsules

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Peng Wang

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Peng Wang, MD

Role: CONTACT

wangp413@163.com

86-21-64175590

Facility Contacts

Peng Wang, M.D.

Role: primary

peng_wang@fudan.edu.cn

862164175590 ext. 83630

Peng Wang, M.D.

Role: primary

wangp413@163.com

862164175590 ext. 83623

Other Identifiers

2208259-7

Identifier Type: -

Identifier Source: org_study_id