Safety and Efficacy of Nivolumab Combined With CAPOX Plus Bevacizumab as Neoadjuvant Treatment of pMMR/MSS Colorectal Cancer Liver Metastases Patients：a Single-arm, Phase II, Prospective Study
Overview
- Phase
- Phase 2
- Intervention
- CapOx(Capecitabine+ Oxaliplatin)
- Conditions
- Colorectal Cancer Liver Metastases
- Sponsor
- Shanghai Changzheng Hospital
- Enrollment
- 12
- Primary Endpoint
- R0 recession rate
- Status
- Not yet recruiting
- Last Updated
- 3 years ago
Overview
Brief 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
Investigators
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-
- •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
Exclusion Criteria
- •Previously received anti-PD1 or anti-PDL1 or anti-PDL2 or anti-CTLA
- •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.
Arms & Interventions
Nivolumab + Bevacizumab + CAPOX as neoadjuvant treatment for 4 cycles
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; Bevacizumab：Bevacizumab is given intravenously at 10mg/kg on day 1 every 3 weeks for 4 cycles; Nivolumab：Nivolumab is given intravenously at 360 mg on day 1 every 3 weeks for 4 cycles;
Intervention: CapOx(Capecitabine+ Oxaliplatin)
Nivolumab + Bevacizumab + CAPOX as neoadjuvant treatment for 4 cycles
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; Bevacizumab：Bevacizumab is given intravenously at 10mg/kg on day 1 every 3 weeks for 4 cycles; Nivolumab：Nivolumab is given intravenously at 360 mg on day 1 every 3 weeks for 4 cycles;
Intervention: Bevacizumab
Nivolumab + Bevacizumab + CAPOX as neoadjuvant treatment for 4 cycles
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; Bevacizumab：Bevacizumab is given intravenously at 10mg/kg on day 1 every 3 weeks for 4 cycles; Nivolumab：Nivolumab is given intravenously at 360 mg on day 1 every 3 weeks for 4 cycles;
Intervention: Nivolumab
Outcomes
Primary Outcomes
R0 recession rate
Time Frame: 10 weeks
Percentage of patients who achieve R0 resection
Pathological complete response rate
Time Frame: 15 weeks
Percentage of patients who achieve pathological complete response (pCR) based on local investigator
Tumor regression grade (TRG）
Time Frame: 15 weeks
Secondary Outcomes
- Objective response rate(Up to 3 years)
- Event free survival(Up to 3 years)
- Disease-free surviva(Up to 3 years)
- One-year or two-year disease-free survival rate(Up to 2 years)
- One-year or two-year overall survival rate(Up to 2 years)
- Incidence of Treatment-Related Adverse Events(Until 30 days after the last treatment)
- Quality of life score (QoL score）(Until 30 days after the last treatment)