Neoadjuvant Serplulimab & Bevacizumab With FOLFOX vs. FOLFOX Alone in RAS/BRAF WT, pMMR/MSS CRC Patients

Launched by SUN YAT-SEN UNIVERSITY · Feb 20, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for patients with colorectal cancer that has spread to the liver. Researchers want to find out if adding two medications, Serplulimab (which helps boost the immune system) and Bevacizumab (which helps cut off the cancer's blood supply), to the standard chemotherapy called FOLFOX can improve patients' outcomes after surgery. The goal is to see if this combination can help the body fight the cancer better and improve recovery after surgery.

To be eligible for this trial, participants must be between 18 and 75 years old and have a confirmed diagnosis of colorectal cancer with up to five liver tumors that can be surgically removed. They should not have any cancer spread to other parts of the body and must meet certain health criteria, like having normal liver function and no serious heart issues. Those who join the study can expect to receive either the new combination treatment or the standard chemotherapy and will be monitored closely throughout the process. If you or a loved one are considering participating, it’s important to discuss this option with a healthcare provider to understand the potential benefits and risks.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Age ≥18 and ≤75 years old
• • Histologically confirmed colorectal adenocarcinoma
• • Radiological and/or pathological confirmation of liver metastases, with ≤5 lesions
• • Genetic testing and/or immunohistochemistry confirmation of RAS, BRAF wild-type, and pMMR/MSS
• • Absence of extrahepatic metastases confirmed by CT, MRI, or PET/CT (if necessary)
• • Primary colorectal tumor has been or can be radically resected
• • Liver metastatic lesions are resectable (including radiofrequency ablation and SBRT), and postoperative NED (no evidence of disease) is expected. Resectable liver metastases are specifically defined as ① ≤5 metastatic lesions; ② R0 resection can be performed (including radiofrequency ablation and SBRT); ③ Sufficient residual liver volume is expected after resection; ④ At least one hepatic vein can be preserved after resection, with preserved blood flow in and out of the residual liver and preserved bile ducts, and can preserve at least two adjacent liver segments; ⑤ No extrahepatic metastases.
• • No prior anti-tumor therapy for liver metastases, except for surgical resection of primary lesions
• • Normal hematological function (platelets \>90×109/L; white blood cells \>3×109/L; neutrophils \>1.5×109/L)
• • Serum bilirubin ≤1.5 times the upper limit of normal (ULN), transaminases ≤5 times ULN, alkaline phosphatase ≤2.5 ULN, no ascites, normal coagulation function, albumin ≥35g/L
• • Liver function classified as Child-Pugh grade A
• • Serum creatinine below the upper limit of normal (ULN), or calculated creatinine clearance rate \>50ml/min (using Cockcroft-Gault formula)
• • ECOG performance status 0-1
• • Expected lifespan \>3 months
• • Signed written informed consent
• • Willing and able to be followed up until death or end of study or study termination.
• Exclusion Criteria:
• • Diagnosis of colorectal cancer with distant extrahepatic metastases
• • Prior chemotherapy, targeted therapy, intervention, or immunotherapy for liver metastases
• • No planned surgical resection for liver metastatic lesions
• • Received oxaliplatin-containing adjuvant chemotherapy regimen within the past one year
• • Any toxicity residuals from previous chemotherapy, excluding alopecia, such as peripheral neuropathy ≥NCI CTC v3.0 grade 2
• • Use of immunosuppressive drugs one week prior to study treatment initiation, excluding topical corticosteroids via nasal, inhalational, or other routes or physiological doses of systemic corticosteroids (i.e., not exceeding 10 mg/day of prednisone or equivalent) or steroids used for prevention of contrast agent allergy
• • Interstitial lung disease requiring corticosteroid treatment
• • Known active autoimmune disease requiring symptomatic treatment or with a history of such disease within the past 2 years. Patients with vitiligo, psoriasis, alopecia, or Graves' disease who have not required systemic treatment within the past 2 years, patients with hypothyroidism requiring only thyroid hormone replacement therapy, and patients with type I diabetes requiring only insulin replacement therapy can be included
• • Known history of primary immunodeficiency
• • Patients with active tuberculosis
• • History of allogeneic organ or hematopoietic stem cell transplantation
• • Known allergy to any monoclonal antibody or chemotherapy drug (Fluorouracil, oxaliplatin) preparation or excipient component
• • Bleeding tendency or coagulation disorder
• • Significant symptoms of intestinal obstruction
• • Hypertensive crisis or hypertensive encephalopathy
• • Severe uncontrolled systemic complications such as infection or diabetes
• • Clinically severe cardiovascular diseases such as cerebrovascular accident (within 6 months before enrollment), myocardial infarction (within 6 months before enrollment), hypertension that remains uncontrolled after appropriate drug treatment, unstable angina pectoris, congestive heart failure (NYHA 2-4), or arrhythmia requiring medication
• • Past or physical examination showing central nervous system diseases (such as primary brain tumor, epilepsy uncontrolled by standard treatment, any history of brain metastasis, or stroke)
• • Diagnosis of other malignant tumors within the past 5 years (excluding basal cell carcinoma and/or carcinoma in situ of the cervix after radical surgery)
• • Patients who received any investigational drug therapy within the last 28 days prior to the study
• • Pregnant or lactating women and women of childbearing age not using or refusing to use effective non-hormonal contraception (intrauterine devices, barrier contraception combined with spermicidal gel, or sterilization surgery) or men with reproductive potential unwilling or unable to comply with the study protocol