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

NCT05588297 | Unknown Phase 2

• 1 other identifier: ZHOUHAIYANG2
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

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

Conditions

Colorectal Cancer Liver Metastases

Outcome Measures

Primary Outcomes (3)

• R0 recession rate

  Percentage of patients who achieve R0 resection

  10 weeks

• Pathological complete response rate

  Percentage of patients who achieve pathological complete response (pCR) based on local investigator

  15 weeks

• Tumor regression grade (TRG）

  15 weeks

Secondary Outcomes (7)

• 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

Study Arms (1)

Nivolumab + Bevacizumab + CAPOX as neoadjuvant treatment for 4 cycles

EXPERIMENTAL

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;

Drug: CapOx(Capecitabine+ Oxaliplatin); Drug: Bevacizumab; Drug: Nivolumab

Interventions

CapOx(Capecitabine+ Oxaliplatin) DRUG

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

Nivolumab + Bevacizumab + CAPOX as neoadjuvant treatment for 4 cycles

Bevacizumab DRUG

Bevacizumab is given intravenously at 10mg/kg on day 1 every 3 weeks for 4 cycles

Nivolumab + Bevacizumab + CAPOX as neoadjuvant treatment for 4 cycles

Nivolumab DRUG

Nivolumab is given intravenously at 360 mg on day 1 every 3 weeks for 4 cycles

Nivolumab + Bevacizumab + CAPOX as neoadjuvant treatment for 4 cycles

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanghai Changzheng Hospital: lead

MeSH Terms

Interventions

Bevacizumab; Nivolumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Haiyang Zhou, MD

CONTACT

+86 13764515639; haiyang1985_1@aliyun.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2022
• First Posted: October 20, 2022
• Study Start: October 1, 2022
• Primary Completion: March 1, 2023
• Study Completion: October 1, 2025
• Last Updated: October 20, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share