- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05588297
Preoperative Nivolumab Plus Bevacizumab Combined With Chemotherapy Before Surgery in Patients With pMMR/MSS Colorectal Cancer Liver Metastases
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
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Haiyang Zhou, MD
- Phone Number: +86 13764515639
- Email: haiyang1985_1@aliyun.com
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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; |
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 is given intravenously at 10mg/kg on day 1 every 3 weeks for 4 cycles
Nivolumab is given intravenously at 360 mg on day 1 every 3 weeks for 4 cycles
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pathological complete response rate
Time Frame: 15 weeks
|
Percentage of patients who achieve pathological complete response (pCR) based on local investigator
|
15 weeks
|
R0 recession rate
Time Frame: 10 weeks
|
Percentage of patients who achieve R0 resection
|
10 weeks
|
Tumor regression grade (TRG)
Time Frame: 15 weeks
|
15 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response rate
Time Frame: Up to 3 years
|
Percentage of patients who achieve partial response (PR) or complete response (CR) based on Response Evaluation Criteria In Solid Tumors (RECIST).
|
Up to 3 years
|
Event free survival
Time Frame: Up to 3 years
|
Measure of time from study treatment to disease progression or death.
|
Up to 3 years
|
One-year or two-year disease-free survival rate
Time Frame: Up to 2 years
|
Percentage of patients who achieve disease-free survival lasting for more than one and two years respectively from the date of surgery.
|
Up to 2 years
|
One-year or two-year overall survival rate
Time Frame: Up to 2 years
|
Percentage of patients who achieve survival for more than one and two years respectively from date of first dose.
|
Up to 2 years
|
Incidence of Treatment-Related Adverse Events
Time Frame: Until 30 days after the last treatment
|
Number of adverse events
|
Until 30 days after the last treatment
|
Disease-free surviva
Time Frame: Up to 3 years
|
Measure of time from the date of surgery to disease relapse or death.
|
Up to 3 years
|
Quality of life score (QoL score)
Time Frame: Until 30 days after the last treatment
|
Assessment of life quality based on EORTC QLQ-C30
|
Until 30 days after the last treatment
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Liver Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Neoplastic Processes
- Colorectal Neoplasms
- Neoplasm Metastasis
- Liver Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Immune Checkpoint Inhibitors
- Capecitabine
- Oxaliplatin
- Nivolumab
- Bevacizumab
Other Study ID Numbers
- ZHOUHAIYANG2
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Colorectal Cancer Liver Metastases
-
Mayo ClinicRecruitingColorectal Cancer | Colorectal Liver MetastasesUnited States
-
Fondazione IRCCS Istituto Nazionale dei Tumori,...Completed
-
Fudan UniversityNot yet recruitingColorectal Cancer Liver MetastasesChina
-
Fudan UniversityUnknown
-
University Hospital, GhentCompletedColorectal Cancer | Metastatic Cancer | Liver Metastases | Liver Cancer
-
Humanitas Clinical and Research CenterCompletedColorectal Cancer | Liver Metastases | Immunotherapy | Colorectal Liver Metastases
-
Sun Yat-sen UniversityRecruitingColorectal Cancer Liver Metastases | RegorafenibChina
-
Ye XuUnknownResected Liver Metastases From Colorectal CancerChina
-
The Central Hospital of Lishui CityZhejiang Cancer Hospital; Zhejiang University; First Affiliated Hospital of Wenzhou...Not yet recruiting
-
Oslo University HospitalThe Research Council of Norway; Norwegian Cancer Society; KlinbeforskActive, not recruitingColorectal Cancer | Liver Metastases | Colorectal Cancer Liver MetastasesNorway, Denmark, Sweden
Clinical Trials on CapOx(Capecitabine+ Oxaliplatin)
-
池畔Not yet recruiting
-
NSABP Foundation IncAmgenWithdrawn
-
Fujian Medical University Union HospitalRecruitingRectal Cancer | Radiation OncologyChina
-
Zealand University HospitalRecruitingIntestinal Neoplasms | Colorectal Cancer | Rectal Cancer | Rectal Neoplasms | Colorectal Neoplasm | Chemotherapy Effect | Intestinal DiseaseDenmark
-
University of Roma La SapienzaNot yet recruitingColon Cancer | Intraperitoneal Rectal CancerItaly
-
Suzhou Transcenta Therapeutics Co., Ltd.Not yet recruitingGastric Cancer | Advanced Cancer | Gastroesophageal-junction Cancer
-
Samsung Medical CenterUnknownColon CancerKorea, Republic of
-
GERCOR - Multidisciplinary Oncology Cooperative...Active, not recruiting
-
LI XIN-XIANGRecruiting
-
Samsung Medical CenterNational Cancer Center, Korea; Asan Medical Center; Chonnam National University... and other collaboratorsCompletedColorectal CancerKorea, Republic of