A Single-center, Single-arm, Open-label Clinical Study of Fruquintinib Combined With Tislelizumab and HAIC in Patients With Advanced Colorectal Liver Metastases Cancer Who Failed Standard Therapy
Overview
- Phase
- Phase 2
- Intervention
- HAIC
- Conditions
- Colorectal Cancer
- Sponsor
- Fudan University
- Enrollment
- 39
- Locations
- 1
- Primary Endpoint
- objective response rate (ORR)
- Status
- Active, Not Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a single-center, single-arm, open-label clinical study, to explore the efficacy and safety of fruquintinib combined with tislelizumab and HAIC (hepatic arterial infusion chemotherapy) in patients with colorectal liver metastases cancer (CRLM) who failed standard therapy.
Detailed Description
Liver is the most common metastatic site in patients with colorectal cancer (CRC) and the leading cause of death in patients. Surgery is the best way to cure CRLM, but few patients can receive surgery, and patients prone to recurrence after surgery. It is an urgent topic to choose an effective treatment method with less side effects for CRLM patients. HAIC is a unique and effective treatment option for CRLM patients. Fruquintinib is a small molecule angiogenesis inhibitor, and has been recommended for third-line treatment of metastatic colorectal cancer (mCRC). Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody, meanwhile, tislelizumab shows significant and durable antitumor activity in patients with CRC, and is well tolerated.
Investigators
Lu Wang, MD, PhD
Head of liver surgery department
Fudan University
Eligibility Criteria
Inclusion Criteria
- •Informed consent has been signed
- •Histologically or cytologically confirmed unresectable advanced colorectal liver metastases cancer
- •Age ≥ 18 years, ≤75 years
- •ECOG PS：0-1
- •Expected overall survival ≥3 months
- •Patients must have at least one measurable liver metastases (RECIST 1.1)
- •Patients who have previously failed standard treatment, or who cannot tolerate standard treatment
- •Patients must have adequate organ and bone marrow function
- •Women of childbearing age must have a negative pregnancy test within the first day of the study, and contraceptive methods should be taken during the study until 6 months after the last administration
Exclusion Criteria
- •Patients who are allergic or suspected to be allergic to the study drug or similar drugs
- •Patients had other malignant tumors in the past 5 years or at the same time (except for the cured skin basal cell carcinoma and cervical carcinoma in situ);
- •Participating in other clinical trials and received at least one treatment within 4 weeks before enrollment
- •Patients with autoimmune disease or history of autoimmune disease within 4 weeks before enrollment
- •patients currently have central nervous system (CNS) metastasis or previous brain metastasis and the symptom control time is less than 2 months
- •Patients cannot take fruquintinib orally
- •Patients who have received organ transplantation and bone marrow transplantation in the past
- •Have taken other strong inducers or inhibitors of CYP3A4, P-gp substrates and BCRP substrates within 2 weeks before the First medication
- •Received any operation (except biopsy) or invasive treatment or operation (except venous catheterization, puncture and drainage, etc.) within 4 weeks before enrollment
- •Pleural effusion or ascites causing relevant clinical symptoms, including respiratory syndrome (dyspnea≥CTC AE grade 2)
Arms & Interventions
combination therapy
Combination: Fruquintinib plus Tislelizumab and HAIC (TOMOX/TOMIRI) Maintenance: Fruquintinib plus Tislelizumab
Intervention: HAIC
combination therapy
Combination: Fruquintinib plus Tislelizumab and HAIC (TOMOX/TOMIRI) Maintenance: Fruquintinib plus Tislelizumab
Intervention: Fruquintinib
combination therapy
Combination: Fruquintinib plus Tislelizumab and HAIC (TOMOX/TOMIRI) Maintenance: Fruquintinib plus Tislelizumab
Intervention: Tislelizumab
combination therapy
Combination: Fruquintinib plus Tislelizumab and HAIC (TOMOX/TOMIRI) Maintenance: Fruquintinib plus Tislelizumab
Intervention: Raltitrexed
combination therapy
Combination: Fruquintinib plus Tislelizumab and HAIC (TOMOX/TOMIRI) Maintenance: Fruquintinib plus Tislelizumab
Intervention: Oxaliplatin
combination therapy
Combination: Fruquintinib plus Tislelizumab and HAIC (TOMOX/TOMIRI) Maintenance: Fruquintinib plus Tislelizumab
Intervention: Irinotecan
Outcomes
Primary Outcomes
objective response rate (ORR)
Time Frame: 24 months
Defined as percentage of participants achieving assessed complete response (CR) and partial response (PR) by the investigator according to the RECIST 1.1.
Secondary Outcomes
- overall survival (OS)(24 months)
- Progression-Free Survival (PFS)(24 months)
- Adverse events as assessed by NCI CTCAE v5.0(24 months)
- disease control rate (DCR)(24 months)
- Progression-Free Survival rate at 6 months(6 months)