COBP: Preoperative Pembrolizumab Plus Bevacizumab Combined With Chemotherapy in Patients With pMMR/MSS Locally Advanced Colorectal Cancer
Study Details
Study Description
Brief Summary
This prospective, single-arm study aims to investigate the safety and efficacy of pembrolizumab plus bevacizumab and chemotherapy as neoadjuvant treatment in pMMR/MSS locally advanced colorectal cancer patients
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Pembrolizumab+ 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; Pembrolizumab：Pembrolizumab is given intravenously at 200 mg on day 1 every 3 weeks for 4 cycles |
Drug: Capecitabine
Capecitabine is given orally at 1500mg / m² twice a day from day1-14 every 3weeks for 3 cycles
Drug: Oxaliplatin
Oxaliplatin is given by intravenous infusion at 200mg / m2 on Day 1 every 3 weeks for 3cycles
Drug: Bevacizumab
Bevacizumab is given intravenously at 10mg/kg on day 1 every 3 weeks for 3 cycles
Drug: Pembrolizumab
Pembrolizumab is given intravenously at 200 mg on day 1 every 3 weeks for 3 cycles
|
Outcome Measures
Primary Outcome Measures
- R0 resection rate [15 weeks]
Percentage of patients who achieve R0 resection
- Pathological complete response rate [15 weeks]
Percentage of patients who achieve pathological complete response (pCR) based on local investigator
- Tumor regression grade (TRG) [15 weeks]
Secondary Outcome Measures
- Objective response rate [3 years]
Percentage of patients who achieve partial response (PR) or complete response (CR) based on Response Evaluation Criteria In Solid Tumors (RECIST)
- Event free survival [Up to 3 years]
Measure of time from study treatment to disease progression or death
- Disease-free survival [Up to 3 years]
Measure of time from the date of surgery to disease relapse or death
- One-year or two-year disease-free survival rate [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
- One-year or two-year overall survival rate [Up to 2 years]
Percentage of patients who achieve survival for more than one and two years respectively from date of first dose
- Incidence of Treatment-Related Adverse Events [Until 30 days after the last treatment]
Number of adverse events
- Quality of life score (QoL score) [Until 30 days after the last treatment]
Assessment of life quality based on EORTC QLQ-C30
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologically confirmed colorectal adenocarcinoma with T4bNxM0 and radical operation cannot be achieved by investigator's evaluation
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Immunohistochemistry and/or genetic testing confirmed pMMR/MSS
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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
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Measurable disease according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria and haven't received any local treatment.
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Eastern Cooperative Oncology Group (ECOG) 0-1.
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Absence of distant metastasis confirmed by CT, MRI or PET/CT
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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).
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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.
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Life expectancy> 3 months
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Signed and written informed consent
Exclusion Criteria:
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Previously received anti-PD1 or anti-PDL1 or anti-PDL2 or anti-CTLA4.
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Uncontrolled active bleeding from the primary tumor or intestinal obstruction.
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Contraindications of bevacizumab
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Hypersensitivity to other monoclonal antibodies.
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Any active, known or suspected autoimmune disease.
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Uncontrolled pleural effusion, pericardial effusion, or ascites to a moderate or greater extent.
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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.
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Major surgery within 4 weeks before enrollment and haven't fully recovered from the previous surgery.
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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.
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Previously received allogeneic stem cell or parenchymal organ transplantation.
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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.
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History of uncorrected serum electrolyte disturbances such as potassium, calcium and magnesium.
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HIV infection.
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Active hepatitis B or hepatitis C.
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Pregnancy or lactation period, or unwilling to use contraception during the trial.
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With other malignancy within 5 year, except cervical carcinoma in situ, basal or squamous skin cancer, local prostatic carcinoma and ductal carcinoma in situ.
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Use corticosteroids (dose of prednisone or similar drugs> 10mg/day) or other immunosuppressive agents within 14 days before enrollment.
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Patients with active tuberculosis (TB) who are receiving anti-TB treatment or have received anti-TB treatment within 1 year.
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Active infection, or treatment with oral or intravenous antibiotics within the first 2 weeks prior to neoadjuvant therapy, except prophylactic administration.
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Anti-infective vaccine (eg. influenza vaccine, varicella vaccine, etc.) injection within 4 weeks before neoadjuvant therapy.
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Previous participation in other clinical trials within 4 weeks before neoadjuvant therapy.
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Any other disease, metabolic disorder, abnormal physical examination or abnormal laboratory results that may constrain the use of trial drug, or affect the reliability of study results, or lead to high risk of treatment complications, or affect patient compliance.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Shanghai Changzheng Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ZHOUHAIYANG