Preoperative Nivolumab Plus Bevacizumab Combined With Chemotherapy Before Surgery in Patients With pMMR/MSS Colorectal Cancer Liver Metastases

Launched by SHANGHAI CHANGZHENG HOSPITAL · Oct 18, 2022

Keywords

ClinConnect Summary

This clinical trial is studying a combination of treatments for patients with colorectal cancer that has spread to the liver. The goal is to see if using a medication called Nivolumab and another called Bevacizumab, along with chemotherapy, before surgery can be safe and effective for patients. This type of treatment is called "neoadjuvant therapy," and the researchers want to find out if it can help shrink tumors and improve surgical outcomes.

To participate in this trial, participants need to be between 18 and 75 years old and have specific types of colorectal cancer with liver metastases. They must also meet certain health criteria, such as having no other major illnesses that could complicate their treatment. Participants can expect to receive the combination treatment before surgery, and their progress will be monitored closely throughout the study. The trial is not yet recruiting participants, so interested individuals will need to wait until it begins. It's important for potential participants to discuss this opportunity with their healthcare team to see if it's the right fit for them.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Age ≥18 years old and ≤75 years old
• • On the basis of data from the literature, we defined liver metastases as B/U if at least one of the following was present: more than four liver metastases, involvement of the hepatic artery or portal vein, or involvement of the biliary duct. A trained radiologist reviewed radiologic images (computed tomography or magnetic resonance imaging scans of the abdomen) taken before the conversion chemotherapy to assess the resectability criteria.
• • Immunohistochemistry and/or genetic testing confirmed pMMR/MSS
• • Initial diagnosed or recurrent patients will be accepted, patients with recurrence should not have received any treatment include chemotherapy, targeted therapy or immunotherapy within 1 month or radiotherapy within 1 year
• • Measurable disease according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria and haven't received any local treatment.
• • Eastern Cooperative Oncology Group (ECOG) 0-1.
• • Absence of distant metastasis confirmed by CT, MRI or PET/CT
• • Adequate hematologic and organ function, defined by protocol-specified laboratory test results, obtained within 7 days before first dose. Absolute neutrophil count ≥1500/mm3, platelet ≥100,000/mm3, Hb ≥10g/dl, serum creatinine ≤1.5 times ULN, creatinine clearance rate ≥50mL/min, ALT and AST ≤2.5 times ULN, INR or aPTT ≤1.5 times ULN (INR ≤2 times ULN and aPTT in normal range for patients who are on prophylactic anticoagulant therapy within 14 days before study treatment), total bilirubin level ≤2 times ULN (within 7 days before study treatment).
• • Women of childbearing age should confirm that serum pregnancy test is negative and agree to use effective contraceptive methods during study treatment and the following 60 days.
• • Life expectancy\> 3 months
• • Signed and written informed consent
• Exclusion Criteria:
• • Previously received anti-PD1 or anti-PDL1 or anti-PDL2 or anti-CTLA4.
• • Uncontrolled active bleeding from the primary tumor or intestinal obstruction.
• • Contraindications of bevacizumab
• • Hypersensitivity to other monoclonal antibodies.
• • Any active, known or suspected autoimmune disease.
• • Uncontrolled pleural effusion, pericardial effusion, or ascites to a moderate or greater extent.
• • History of one of the following diseases: idiopathic pulmonary fibrosis, organized pneumonia (eg. bronchiolitis obliterans), drug-induced pneumonia, idiopathic pneumonia and interstitial pneumonia, or evidence of active pneumonia through enhanced chest CT screening.
• • Major surgery within 4 weeks before enrollment and haven't fully recovered from the previous surgery.
• • Active bleeding or abnormal coagulation (aPTT \>43s or INR \>1.5 times ULN), or having a tendency to bleed or receiving thrombolytic or anticoagulant therapy.
• • Previously received allogeneic stem cell or parenchymal organ transplantation.
• • Any significant clinical or laboratory abnormality that the investigator considers to influence the safety assessment, eg. uncontrolled active infection, uncontrolled diabetes, hypertension that cannot be reduced to normal range with monotherapy, grade II or above peripheral neuropathy, congestive heart failure, heart disease (class II or higher) as defined by the New York College of Cardiology, myocardial infarction within 3 months prior to enrollment, unstable arrhythmias, unstable angina pectinis, chronic kidney disease, abnormal thyroid function and previous or co-existing malignancies.
• • History of uncorrected serum electrolyte disturbances such as potassium, calcium and magnesium.
• • HIV infection.
• • Active hepatitis B or hepatitis C.
• • Pregnancy or lactation period, or unwilling to use contraception during the trial.
• • With other malignancy within 5 year, except cervical carcinoma in situ, basal or squamous skin cancer, local prostatic carcinoma and ductal carcinoma in situ.
• • Use corticosteroids (dose of prednisone or similar drugs\> 10mg/day) or other immunosuppressive agents within 14 days before enrollment.
• • Patients with active tuberculosis (TB) who are receiving anti-TB treatment or have received anti-TB treatment within 1 year.
• • Active infection, or treatment with oral or intravenous antibiotics within the first 2 weeks prior to neoadjuvant therapy, except prophylactic administration.
• • Anti-infective vaccine (eg. influenza vaccine, varicella vaccine, etc.) injection within 4 weeks before neoadjuvant therapy.
• • Previous participation in other clinical trials within 4 weeks before neoadjuvant therapy.
• • Any other disease, metabolic disorder, abnormal physical examination or abnormal laboratory results that may contrain the use of trial drug, or affect the reliability of study results, or lead to high risk of treatment complications, or affect patient compliance.