A Study on the Efficacy and Safety of Multi-mode Ablation Combined With Systemic Therapy in the Treatment of CRCLM

Official title

A Study on the Efficacy and Safety of Multi-mode Ablation Combined With Systemic Therapy Including PD-1 Inhibitor in the Treatment of Colorectal Cancer Liver Metastasis(CRCLM)

Overview

The goal of this study is to evaluate the efficacy and safety of multi-mode ablation combined with systemic therapy including PD-1(programmed death receptor 1) inhibitor for colorectal cancer liver metastasis and furthermore to clarify its application value by comparing preoperative and postoperative immune indicators.

Detailed description

This is a single-center, single-arm, prospective study to evaluate the efficacy and safety of multi-mode ablation combined with systemic therapy including PD-1 inhibitor in the treatment of colorectal cancer liver metastasis. The study includes 20 patients with colorectal cancer liver metastasis that has failed first-line therapy and is unresectable. All patients will receive multi-mode ablation to achieve complete remission of liver lesions followed by systemic therapy including PD-1 inhibitor.

This study will provide preliminary data on the efficacy and safety of multi-mode ablation combined with systemic therapy including PD-1 inhibitor in the treatment of colorectal cancer liver metastasis, which could lead to larger randomized trials.

Interventions

• Device Multi-mode tumor treatment system
  All subjects are treated using the multi-mode tumor treatment system (Shanghai MAaGI Medical Technology Co., Ltd), with the treatment procedure conducted according to the temperature control mode for tumor ablation. Complete ablation of intrahepatic lesions is achieved to realize an intrahepatic no-evidence-of-disease (NED) state. For lesions that could not be ablated in a single session, two treatments are performed to achieve NED within the liver.
• Drug Sintilimab+mFOLFOX6 or FOLFIRI+bevacizumab or cetuximab
  Systemic therapy including PD-1 inhibitor starts on the 7th day after ablation (sintilimab 200 mg IV D1 + mFOLFOX6 or FOLFIRI + bevacizumab or cetuximab (determined according to the subject's first-line chemotherapy regimen), Q3W, chemotherapy for 4-6 cycles. Sintilimab continues until disease progression, not exceeding a maximum of 2 years.）

Primary outcome measures

• Progression Free Survival (PFS) [Time frame: max 24 months]

Secondary outcome measures (5)

• Local Progression Free Survival (LPFS) [Time frame: max 24 months]
• Objective Response Rate (ORR) [Time frame: max 24 months]
• Overall Survival (OS) [Time frame: max 24 months]
• Rate of adverse events [Time frame: max 24 months]
• Immune indicator analysis [Time frame: max 24 months]

Eligibility criteria

Inclusion criteria

• Age 18-75 years, gender not specified;
• Pathologically or clinically confirmed colorectal cancer liver metastases, with liver lesions unsuitable for surgical resection or intolerance or refusal of surgical resection;
• In the case of an unresectable primary tumor or recurrence, the absence of serious complications such as bleeding or obstruction;
• Failure of first-line treatment, with disease progression or new liver metastases;
• No more than 5 liver lesions, with single lesion diameter ≤ 3cm;
• For those who have received previous chemotherapy, radiotherapy or local liver treatment, the interval from the last systemic treatment or local liver treatment should be at least 1 month;
• Child-Pugh A or B; bilirubin ≤ 3.0 mg/dL, creatinine ≤ 2.5 mg/dL, white blood cell count ≥ 2.0 ×10\^9/L, platelets ≥ 100 ×10\^9/L;
• ECOG PS ≤ 2;
• Willing to accept subsequent treatment regimens that include anti-PD-1 monoclonal antibody therapy.

Exclusion criteria

• Liver function Child-Pugh class C;
• Expected survival < 3 months;
• Major organ insufficiency or failure;
• Active infection;
• Irreversible coagulation disorders;
• Refractory massive ascites, pleural effusion or cachexia;
• Unable to cooperate with treatment;
• Any other factors deemed inappropriate for inclusion or that may affect the subject's participation in the study, as determined by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shanghai Sixth People's Hospital — Shanghai

Identifiers

NCT: NCT06590259 · 20231124

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗