Cryoablation Combined with Sintilimab Plus Lenvatinib in Previously Treated Unresectable Liver Metastasis from Solid Tumors

NCT05098847 | Recruiting Phase 2

• 1 other identifier: CASTLE-04
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to evaluate the efficacy and safety of cryoablation combined with Sintilimab plus lenvatinib for patients with unresectable liver metastasis, who had progressed after, or were refractory to first- or later-line therapy.

Conditions

Liver Metastasis

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  ORR according to RECIST 1.1

  max 24 months

Secondary Outcomes (5)

• DoR

  max 24 months

• PFS

  max 24 months

• OS

  max 42 months

• DCR

  max 24 months

• Adverse Events

  max 42 months

Study Arms (1)

Cryoablation in combination with Sintilimab plus lenvatinib

EXPERIMENTAL

Drug: Sintilimab; Drug: Lenvatinib; Drug: Cryoablation

Interventions

Sintilimab DRUG

Sintilimab plus lenvatinib will be initiated on day 14 after cryoablation. Sintilimab will be administered at 200 mg i.v. every 3 weeks.

Cryoablation in combination with Sintilimab plus lenvatinib

Lenvatinib DRUG

Sintilimab plus lenvatinib will be initiated on day 14 after cryoablation. Lenvatinib (bodyweight ≥ 60 kg, 12 mg; \< 60 kg, 8 mg) was given orally daily every 3 weeks until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.

Cryoablation in combination with Sintilimab plus lenvatinib

Cryoablation DRUG

Cryoablation treatment starts at day 0. Cryoablation will be performed with a two-cycle freeze-thaw phase protocol; US or non-contrast CT images will be obtained to visualize the evolving ablation zone

Cryoablation in combination with Sintilimab plus lenvatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained.
• Age ≥ 18 years at time of study entry.
• Participants must have unresectable liver metastasis from solid tumors.
• Participants must have progressed after, or were refractory to first- or later-line therapy in the liver metastatic setting.
• Participants who had received previous antiangiogenic or anti-epidermal growth factor receptor (EGFR) therapy were eligible.
• 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.

You may not qualify if:

• 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 than 4 weeks prior to study treatment start.
• Radiotherapy administered less than 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).
• 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

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Interventions

sintilimab; lenvatinib; Cryosurgery

Intervention Hierarchy (Ancestors)

Ablation Techniques; Surgical Procedures, Operative

Study Officials

• Peng Wang, MD

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Peng Wang, MD

CONTACT

86-21-64175590; peng_wang@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 20, 2021
• First Posted: October 28, 2021
• Study Start: October 29, 2021
• Primary Completion: October 30, 2025
• Study Completion: October 30, 2025
• Last Updated: February 27, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)