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

Launched by FUDAN UNIVERSITY · Oct 20, 2021

Keywords

ClinConnect Summary

This clinical trial is investigating a new treatment approach for patients with liver metastasis from solid tumors that cannot be surgically removed. The study is testing a combination of cryoablation (a procedure that freezes cancer cells) with two medications, Sintilimab and Lenvatinib, in patients whose cancer has not responded to previous treatments. The goal is to see how effective and safe this combination is for those who have already tried other therapies.

To participate in this trial, individuals must be at least 18 years old and have liver metastasis that cannot be surgically removed. They should have experienced disease progression after previous treatments and have measurable disease that can be evaluated through imaging tests. Participants will need to be in reasonably good health, with a life expectancy of at least 12 weeks, and must agree to follow the study guidelines, including attending appointments and adhering to any necessary treatments. It's important to note that certain health conditions and recent treatments may exclude someone from participating. If you or a loved one is considering this trial, it may offer a new option for managing liver cancer.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 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.
• 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 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).
• • 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 monotherapy 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 Sintilimab 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 Sintilimab 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.