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

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

NCT ID: NCT05588297

Condition: Colorectal Cancer Liver Metastases

Conditions: Official terms:
Colorectal Neoplasms
Neoplasm Metastasis
Liver Neoplasms
Bevacizumab
Nivolumab
Capecitabine
Oxaliplatin

Study type: Interventional

Study phase: Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: CapOx(Capecitabine+ Oxaliplatin)
Description: CapOx: Capecitabine is given orally at 1500mg / m² twice a day from day1-14 every 3 weeks for 4 cycles and Oxaliplatin is given by intravenous infusion at 200mg / m2 on Day 1 every 3 weeks for 4 cycles
Arm group label: Nivolumab + Bevacizumab + CAPOX as neoadjuvant treatment for 4 cycles

Intervention type: Drug
Intervention name: Bevacizumab
Description: Bevacizumab is given intravenously at 10mg/kg on day 1 every 3 weeks for 4 cycles
Arm group label: Nivolumab + Bevacizumab + CAPOX as neoadjuvant treatment for 4 cycles

Intervention type: Drug
Intervention name: Nivolumab
Description: Nivolumab is given intravenously at 360 mg on day 1 every 3 weeks for 4 cycles
Arm group label: Nivolumab + Bevacizumab + CAPOX as neoadjuvant treatment for 4 cycles

Summary: This prospective, single-arm study aims to investigate the safety and efficacy of Nivolumab plus bevacizumab and chemotherapy as neoadjuvant treatment in pMMR/MSS Colorectal cancer liver metastases patients

Criteria for 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.

Gender: All

Minimum age: 18 Years

Maximum age: 75 Years

Healthy volunteers: No

Start date: October 2022

Completion date: October 2025

Lead sponsor:
Agency: Shanghai Changzheng Hospital
Agency class: Other

Source: Shanghai Changzheng Hospital

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05588297